{"nct_id":"NCT04001010","start_date":"2022-07-31","phase":"Phase 3","enrollment":334,"brief_title":"Safety and Efficacy of Inhaled Synthetic THC/CBD for Improving Physical Functioning and for Modulating Cachexia Progression in Patients With Advanced Cancer and Associated Cachexia","official_title":"Safety and Efficacy of PPP011-kit for Improving Physical Functioning and for Modulating Cachexia Progression in Patients With Advanced Cancer and Associated Cachexia: a Randomized, Double Blind, Placebo Controlled, Parallel Group Study","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Suspended","completion_date":"2023-12-31","last_update":"2021-02-05","description":"A large number of patients with advanced cancer also suffer from cachexia. Cachexia is a syndrome characterized by loss of skeletal muscle mass (with/or without loss of fat mass) that cannot be reversed by nutritional support and progressively leads to functional impairment. Patients who suffer from anorexia and cachexia have lower survival rates. Some patients with cancer use cannabis to improve the way they feel and relieve their pain. However, there is very sparse high-quality research to prove that cannabis products are truly effective. This study will investigate patients with advanced cancer who use inhaled therapeutic cannabinoid-based medication (PPP011), in addition to palliative care management, and will assess if these patients experience improvement in functional status as a surrogate endpoint for survivalquality","other_id":"PPP011-Ph3-01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Written informed consent,\r\n\r\n          2. Adult male and female patients at least 18 years of age,\r\n\r\n          3. Patient agreed to follow the protocol,\r\n\r\n          4. Advanced cancer for which there is no known curative therapy,\r\n\r\n          5. The patient has a cachexia weight loss of Grade of 2 or Grade 3 cachexia as follow\r\n             (based on Weight Loss Grading System) Weight loss accounts for the last 6 months\r\n             before screening.\r\n\r\n          6. Patient's weight 6 months before screening must be available\r\n\r\n          7. Karnofsky Performance Status score  60 %\r\n\r\n          8. Life expectancy of at least 4 months, excluding refractory cachexia\r\n\r\n          9. No cognitive impairment according to Mini-Cog Negative confusion assessment according\r\n             to CAM,\r\n\r\n         10. The patient is able to perform deep inhalations with FEV1 more than 60%,\r\n\r\n         11. Ability to read and respond to questions in French or English or French or Spanish,\r\n\r\n         12. A female volunteer must meet one of the following criteria:\r\n\r\n        If of childbearing potential - agrees to use one of the accepted contraceptive regimens\r\n        from at least 28 days prior to the first drug administration, during the study and for at\r\n        least 60 days after the last dose, If of non-childbearing potential - should be surgically\r\n        sterile or in a menopausal state, A male volunteer with sexual partners who are pregnant,\r\n        possibly pregnant, or who could become pregnant must be surgically sterile or agrees to use\r\n        one of the accepted contraceptive regimens from first drug administration until 3 months\r\n        after the last drug administration.\r\n      ","sponsor":"Tetra Bio-Pharma","sponsor_type":"Industry","conditions":"Cannabis Use|Cachexia; Cancer|Advanced Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: PPP011","description":"1 capsule inhaled 3 times a day with a vaporizer device"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"1 capsule inhaled 3 times a day with a vaporizer device"}],"outcomes":[{"outcome_type":"primary","measure":"physical functioning related to advanced cancer will be measured using a patient self rating questionnaire.","time_frame":"Change from baseline in EORTC-QLQ-C15-PAL physical functioning in multi-item scales at week 4, 8 and 12 W4 W8 W12","description":"European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 Palliative (EORTC-QLQ-C15-PAL). items are rated on a scale of 1 (not at all) to 4 (very much). high scores on a symptom scale correlate to increased symptom burden"},{"outcome_type":"primary","measure":"Cachexia grade will be measured as per Weight Loss Grading System","time_frame":"Change from baseline at week 4, 8 and 12.","description":"Downgrading cachexia grade or grade maintenance will be considered as a drug benefit."},{"outcome_type":"secondary","measure":"pain will be recorded: VAS","time_frame":"Observed and Change from baseline in a VAS on pain AND no increase in pain medications at week 4, 8 and, 12 and 24.","description":"using a visual analogue scale. horizontal 0-100 mm VAS assessing pain"},{"outcome_type":"secondary","measure":"Patient nutritional and functional assessment will be meseared using a patient self rating questionnaire","time_frame":"Observed and change from baseline in patient nutritional and functional assessment (PG-SGA) at baseline and week 4, 8 and, 12.","description":"Patient-generated-subjective global assessment (PG-SGA) where critical need for nutrition intervention is defined as having a score ≥ 9 The higher the score the greater the risk for malnutrition"}]}
{"nct_id":"NCT04910386","start_date":"2022-06-01","phase":"Phase 2","enrollment":126,"brief_title":"Multicenter Phase 2 Study of Envafolimab in Biliary Tract Cancers","official_title":"A Randomized, Open-Label, Multicenter Phase 2 Study of Envafolimab in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients With Locally Advanced or Metastatic Biliary Tract Cancers","primary_completion_date":"2025-06-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-06-01","last_update":"2021-06-04","description":"This is a Randomized, Open-Label, Multicenter Phase 2 Study to access the efficacy and safety of Envafolimab in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients with Locally Advanced or Metastatic Biliary Tract Cancers","other_id":"KN035-US-002","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Be  18 years of age;\r\n\r\n          2. Subjects must have a histopathological or cytological diagnosis of locally advanced or\r\n             metastatic gallbladder cancer (GBC) or cholangiocarcinoma (CCA);\r\n\r\n          3. Subjects who have not received prior systemic therapy for advanced disease or who have\r\n             received adjuvant or neoadjuvant chemotherapy in one regimen and relapsed > 6 months\r\n             after the end of chemotherapy can be enrolled;\r\n\r\n          4. Child-Pugh liver function rating: class A (5-6 points) and better class B (7 points)\r\n             (see Appendix 3);\r\n\r\n          5. ECOG PS score 0 or 1 (see Appendix 1);\r\n\r\n          6. Expected survival  12 weeks;\r\n\r\n          7. Subjects with at least one measurable lesion (RECIST 1.1 criteria, see Appendix 2);\r\n\r\n          8. Subject must have adequate major organ and bone marrow functions (no blood transfusion\r\n             and no use of hematopoietic growth factor within 14 days before the first dose of\r\n             study treatment):\r\n\r\n        1) Hematology: neutrophils  1.5  109/L, platelets  100  109/L, and hemoglobin  90 g/L;\r\n        2) International normalized ratio (INR)  1.5  upper limit of normal (ULN) and activated\r\n        partial thromboplastin time (APTT)  1.5  ULN; 3) Liver function: serum total bilirubin \r\n        1.5  ULN or direct bilirubin  ULN for subjects with total bilirubin levels >1.5 ULN;\r\n        Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT])  2.5 \r\n        ULN OR  5  ULN for subjects with liver metastases; 4) Renal function: serum creatinine \r\n        1.5 x ULN and creatinine clearance (CCr) > 60 mL/min (assessed with Cockcroft-Gault\r\n        formula, see Appendix 6); 5) Normal cardiac function with left ventricular ejection\r\n        fraction (LVEF)  50% by two-dimensional echocardiography.\r\n\r\n        9. Subjects must fully understand the study, voluntarily participate, and sign the informed\r\n        consent form (ICF).\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has participated in another clinical trials of other investigational drugs or\r\n             investigational devices within 4 weeks prior to the first dose of investigational\r\n             product treatment (palliative radiotherapy for bone metastases completed at least 2\r\n             weeks prior to investigational product treatment is allowed);\r\n\r\n          2. The investigator assesses liver metastases as 50% or more of the total liver volume;\r\n\r\n          3. Has ascites requiring drainage or treatment with diuretics, or pleural or pericardial\r\n             effusion requiring drainage and/or associated with symptoms of tachypnea within 4\r\n             weeks prior to the first dose of investigational product treatment;\r\n\r\n          4. Has biliary obstruction with clinical intervention that has not resolved or requires\r\n             anti-infective therapy as judged by the investigator 14 days prior to the first dose\r\n             of investigational product treatment;\r\n\r\n          5. Has prior liver transplantation;\r\n\r\n          6. Has known active brain metastases or spinal cord compression; subjects with previously\r\n             treated brain metastases may be enrolled if their clinical condition is stable and\r\n             radiographic evidence shows no disease progression within 4 weeks prior to the first\r\n             dose of investigational product treatment, and corticosteroid therapy is not required\r\n             within 4 weeks prior to the first dose of investigational product treatment;\r\n\r\n          7. Has a known additional malignant tumor in the past 5 years (except for skin basal cell\r\n             or squamous cell carcinoma, or cervical, breast and other carcinoma in situ after\r\n             radical surgery);\r\n\r\n          8. Has received major surgical procedures (except biopsy) or incomplete healing of\r\n             surgical wound within 4 weeks prior to the first dose of investigational product\r\n             treatment;\r\n\r\n          9. Has any unresolved toxicity (CTCAE Grade  2) from prior anti-tumor therapy, except\r\n             for alopecia or Grade 2 peripheral neuropathy or other laboratory abnormalities that\r\n             are not clinically significant as assessed by the investigator;\r\n\r\n         10. Has an active autoimmune disease or a documented history of autoimmune disease or\r\n             syndrome that requires systemic steroids or immunosuppressive agents. Subjects with\r\n             vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects\r\n             who require intermittent use of bronchodilators or local steroid injections would not\r\n             be excluded from the study. Subjects with hypothyroidism that is stable on hormone\r\n             replacement will not be excluded from the study;\r\n\r\n         11. Has known history of HIV, or active bacterial or fungal infection requiring systemic\r\n             treatment within 14 days prior to the first dose of investigational product treatment;\r\n\r\n         12. Has history of interstitial lung disease, drug-induced interstitial lung disease,\r\n             radiation pneumonitis, symptomatic interstitial lung disease or presence of active\r\n             pneumonitis on chest CT scan within 4 weeks before the first dose of investigational\r\n             product treatment;\r\n\r\n         13. Has active hepatitis B (HBsAg positive and HBV-DNA  104 copies/mL) or hepatitis C\r\n             (HCV antibody positive and HCV-RNA quantitative test results greater than the lower\r\n             limit of detection);\r\n\r\n         14. Has a history or current evidence of clinically significant cardiovascular diseases,\r\n             including but not limited to acute myocardial infarction, severe/unstable angina,\r\n             acute ischemic/hemorrhagic stroke, congestive heart failure ( New York Heart\r\n             Association Class II, see Appendix 4) within 6 months prior to enrollment; arrhythmias\r\n             requiring treatment with other antiarrhythmic drugs in addition to -blockers or\r\n             digoxin; repeat QTcF interval > 450 milliseconds (ms) on ECG (see Appendix 5);\r\n             hypertension not well controlled with antihypertensive drug therapy (systolic blood\r\n             pressure > 150 mmHg, diastolic blood pressure > 100 mmHg);\r\n\r\n         15. Be receiving therapeutic doses of warfarin (low-dose warfarin  2 mg/day is allowed);\r\n             or receiving antiplatelet anticoagulant therapy (aspirin doses  300 mg/day and\r\n             clopidogrel doses  75 mg/day are allowed);\r\n\r\n         16. Has received immunosuppressive drugs within 4 weeks prior to the first dose of\r\n             investigational product treatment, excluding topical corticosteroids or systemic\r\n             prednisone  10 mg/day or equivalent doses of other corticosteroids;\r\n\r\n         17. Has received live vaccines within 4 weeks before the first dose of investigational\r\n             product treatment or plan to receive it during the study;\r\n\r\n         18. Has history of severe allergic reactions to chimeric or human antibodies or fusion\r\n             proteins, or known allergies to biological products produced with Chinese hamster\r\n             ovary cells or any component of envafolimab; known or suspected allergy to the\r\n             chemotherapeutic drug gemcitabine/cisplatin and its components;\r\n\r\n         19. Be pregnant or breastfeeding;\r\n\r\n         20. Be childbearing potential but unwilling to accept effective contraceptive measures;\r\n\r\n         21. Any other disease, metabolic disorder or laboratory abnormalities, that the\r\n             investigator considers that the subject is not suitable for the investigational\r\n             product treatment, or will affect the interpretation of the study results, or put the\r\n             subject at high risk.\r\n      ","sponsor":"3D Medicines (Sichuan) Co., Ltd.","sponsor_type":"Industry","conditions":"Biliary Tract Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: Envafolimab plus Gemcitabine&Cisplatin","description":"Envafolimab a programmed death ligand immune check inhibitor Per Investigator decision"},{"intervention_type":"Drug","name":"Drug: Gemcitabine&Cisplatin","description":"The standard of care for the patients with unresectable/metastatic biliary tract cancer"}],"outcomes":[{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Observed by 12 weeks","description":"To evaluate the duration of response (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;"},{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"Observed by 12 weeks","description":"To evaluate the progression-free survival (PFS) of envafolimab in combination with gemcitabine plus cisplatin (GemCis) versus first-line treatment of GemCis in patients with advanced biliary tract cancers (BTC)."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Observed by 12 weeks after progressive disease or end of treatment","description":"To evaluate the overall survival (OS) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;"},{"outcome_type":"secondary","measure":"Objective response rate(ORR)","time_frame":"Observed by 12 weeks","description":"To evaluate the objective response rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Observed by 12 weeks","description":"To evaluate the disease control rate (assessed by the investigator per RECIST 1.1 criteria) of envafolimab in combination with GemCis versus GemCis in patients with advanced BTC;"}]}
{"nct_id":"NCT02201381","start_date":"2022-05-23","phase":"Phase 3","enrollment":207,"brief_title":"Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer","official_title":"A Non Randomised, Non Blinded Real World Trial of the Safety, Tolerability and Effectiveness of Metabolic Medicines for the Treatment of Cancer Compared Against Matched Controls","primary_completion_date":"2027-05-23","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-09-23","last_update":"2021-09-16","description":"The purpose of this study is to determine the effectiveness of a regimen of selected metabolic treatments for patients with cancer in a real world setting and to conduct exploratory analysis on the relationship between the degree of response and changes in biochemical markers (such as glucose and lipid levels).","other_id":"Metabolic Cancer 001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Matched historical control comparison","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":85,"population":"","criteria":"\n        Inclusion criteria\r\n\r\n          1. Male or female 18-85 years old;\r\n\r\n          2. Diagnosed with cancer and have had such diagnosis confirmed by scan, blood markers\r\n             and/or biopsy;\r\n\r\n          3. Is receiving or will shortly receive standard of care therapy or has completed\r\n             standard of care treatment; and\r\n\r\n          4. Signed and dated written informed consent from the participant or LAR.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Pregnant or lactating females or females who are planning a pregnancy during the\r\n             course of the study;\r\n\r\n          2. Major organ failure, renal, lung and liver failure;\r\n\r\n          3. Participants having active liver disease or unexplained persistent elevation of serum\r\n             transaminases > 3 times the upper limit of normal;\r\n\r\n          4. Participants with diabetic ketoacidosis or diabetic pre-coma;\r\n\r\n          5. Participants with a creatinine clearance < 60mL/min;\r\n\r\n          6. History of cardiac or respiratory failure;\r\n\r\n          7. History of recent myocardial infarction;\r\n\r\n          8. Ileum, colon or stomach part or full removal rendering them unable to take the study\r\n             medicines;\r\n\r\n          9. Unable to eat or keep food or medicines down or is being fed intravenously;\r\n\r\n         10. Is too frail and weak to withstand the study medicines in the opinion of the study\r\n             doctor;\r\n\r\n         11. Is Unlikely to survive more than 1 month under standard of care, in the opinion of the\r\n             study doctor\r\n\r\n         12. Hypersensitivity to any of the treatment drugs or excipients;\r\n\r\n         13. If the patient is on any medicines contraindicated with the study medicines (see\r\n             Appendix 3);\r\n\r\n         14. Mentally incapacitated and no guardian able to sign on patients Clinical study\r\n             protocol, version 5.0 METRICS TRIAL, Metabolic Cancer 001 5th Apr 2016 Confidential\r\n             Page 5 of 65 behalf;\r\n\r\n         15. History or presence of alcohol or substance abuse;\r\n\r\n         16. Participation in a clinical trial of an investigational medicinal product that is\r\n             viewed by the Study Physician to be a significant risk to the participant's safety;\r\n\r\n         17. Direct employee of the study site.\r\n      ","sponsor":"Health Clinics Limited","sponsor_type":"Industry","conditions":"Cancer|Overall Survival","interventions":[{"intervention_type":"Drug","name":"Drug: Metabolic treatment","description":"While subjects are being treated with the four metabolic drugs, every 3 months they will bring in their medical records and data will be collected to determine the effect of the intervention"}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival","time_frame":"up to 5 years","description":"Overall survival for all cancer types and for each cancer type (years and months)"},{"outcome_type":"secondary","measure":"Change in primary tumour size cancer types and by cancer type.","time_frame":"up to 5 years","description":"Tumour size for all cancer types and for each cancer type. Units of size vary depending on cancer type."},{"outcome_type":"secondary","measure":"Change in tumour spread (metastasis)","time_frame":"up to 5 years","description":"Tumour spread (metastasized) to other tissues/organs, for all cancer types and for each cancer type. This is measured as either 0 for no spread or 1 for confirmed spread."},{"outcome_type":"secondary","measure":"Change in tumour number","time_frame":"up to 5 years","description":"Tumour number for all cancer types and for each cancer type"},{"outcome_type":"secondary","measure":"Change in cancer biomarkers (blood, urine or biopsy)","time_frame":"up to 5 years","description":"Cancer biomarkers for all cancer types and for each cancer type. Units of measurement vary depending on the cancer type. When biomarkers, either alone or in combination with other biomarkers, are raised above normal they are seen as predictive of cancer of progression. If returned to normal are indicative of treatment response."},{"outcome_type":"other","measure":"Incidence of treatment related adverse events","time_frame":"5 years","description":"Adverse events reported by the subject or their HCP.\r\n• Quarterly assessment of routine laboratory tests"}]}
{"nct_id":"NCT03999658","start_date":"2022-01-31","phase":"Phase 2","enrollment":220,"brief_title":"A Study of STI-3031 (an Anti-PD-L1 Antibody) in Patients With Selected Relapsed/Refractory Malignancies","official_title":"An Open-label, Multicenter, Global Phase 2 Basket Study to Investigate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of STI-3031 in Patients With Selected Relapsed or Refractory Malignancies.","primary_completion_date":"2024-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-07-31","last_update":"2020-07-15","description":"This study evaluates the efficacy, as measured by the objective response rate, of STI-3031, an anti-PD-L1 antibody, in previously treated patients with selected advanced lymphomas or biliary tract cancer.","other_id":"STI-3031-001","allocation":"Non-Randomized","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Documented histologically confirmed diagnoses of Extranodal NK/T-cell lymphoma,\r\n             Peripheral T-cell lymphoma, Diffuse Large B-cell lymphoma (with a PD-L1 gene\r\n             abnormality or Epstein-Barr virus positivity, or biliary tract cancer.\r\n\r\n          -  Prior treatment:\r\n\r\n               -  Extranodal NK/T-cell lymphoma: Must have received at least 1 previous line of\r\n                  systemic therapy including an asparaginase-based regimen.\r\n\r\n               -  Peripheral T-cell lymphoma: must have received at least 1 previous line of\r\n                  systemic multi-agent chemotherapy. Participants with anaplastic large cell\r\n                  lymphoma (ALCL) must have received brentuximab vedotin\r\n\r\n               -  Diffuse Large B-cell lymphoma: Must have received at least 2 previous lines of\r\n                  systemic therapy including an anti-CD20 antibody\r\n\r\n               -  Biliary Tract Cancer: Must have received at least 1 previous line of systemic\r\n                  therapy including gemcitabine with or without platinum\r\n\r\n          -  Documented disease progression during or after the last therapy\r\n\r\n          -  If not previously treated with transplant, Investigator considers the participant\r\n             ineligible for transplant\r\n\r\n          -  Measurable disease\r\n\r\n          -  Adult age (as defined by respective country) at time of signing informed consent form\r\n             (ICF)\r\n\r\n          -  Must be able to understand the nature of the study and provide a signed and dated,\r\n             written ICF prior to any study-specific procedures, sample collections and analyses\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1\r\n\r\n          -  Prior radiotherapy is allowed if more than 14 days have elapsed since the end of\r\n             treatment and radiopharmaceuticals are permitted if more than 8 weeks have elapsed\r\n             since the end of treatment\r\n\r\n          -  At least 14 days or 5 half-lives must have elapsed since the last chemotherapy,\r\n             immunotherapy, biological or investigational therapy, and have recovered from\r\n             toxicities associated with such treatment to < Grade 2\r\n\r\n          -  Adequate hematologic, renal and hepatic function\r\n\r\n          -  Females of childbearing potential (FCBP) must agree to use a reliable form of\r\n             contraceptive during the study treatment period and for at least 90 days following the\r\n             last dose of study intervention\r\n\r\n          -  Male participants must agree to use barrier contraception (i.e., condoms) for the\r\n             duration of the study and for at least 90 days after the last dose of study\r\n             intervention\r\n\r\n          -  Predicted life expectancy of at least 16 weeks\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Current participation in another therapeutic clinical trial\r\n\r\n          -  Prior treatment with an anti-PD-L1 or anti-PD-1 antibody\r\n\r\n          -  Patients with symptomatic central nervous system (CNS) metastases unless considered\r\n             adequately treated and controlled for at least 2 weeks\r\n\r\n          -  Prior hematopoietic stem cell transplantation\r\n\r\n          -  History of other previous cancer that would interfere with the determination of safety\r\n             or efficacy\r\n\r\n          -  Any active autoimmune disease or a documented history of autoimmune disease, or\r\n             history of syndrome that required systemic steroids or immunosuppressive medications,\r\n             except for participants with vitiligo, hormone replacement therapy for stable thyroid\r\n             diseases and Type 1 diabetes mellitus\r\n\r\n          -  Apparent active or latent tuberculosis (TB) infection\r\n\r\n          -  Seropositive for or have active infection with hepatitis C virus (HCV), unless HCV\r\n             viral load is below the limit of quantification and participant is on concurrent viral\r\n             suppressive therapy\r\n\r\n          -  Seropositive for or have active viral infection with hepatitis B virus (HBV), unless\r\n             HBV viral load is below the limit of quantification and participant is on concurrent\r\n             viral suppressive therapy\r\n\r\n          -  Seropositive for or active viral infection with HIV, unless the following are met:\r\n\r\n               -  CD4+ T-cell (CD4+) counts  350 cells/uL; and\r\n\r\n               -  Participant has been on established antiretroviral therapy (ART) for at least 4\r\n                  weeks prior to screening and have HIV viral load < 400 copies/mL; and\r\n\r\n               -  Participant has not had acquired immunodeficiency syndrome (AIDS)-defining\r\n                  opportunistic infections within the past 12 months prior to screening\r\n\r\n          -  Active infection (viral, bacterial, or fungal) requiring intravenous (IV) systemic\r\n             therapy within 14 days\r\n\r\n          -  Evidence of bleeding diathesis or coagulopathy.\r\n\r\n          -  Significant proteinuria\r\n\r\n          -  Conditions requiring chronic steroid use (> 10 mg/day of prednisone or equivalent).\r\n\r\n          -  Recent history of attenuated viral vaccination within 30 days prior to the first dose\r\n             of study intervention\r\n\r\n          -  Herbal preparations/medications are not allowed throughout the treatment period unless\r\n             first discussed with and approved by the Medical Monitor\r\n\r\n          -  History of severe hypersensitivity reactions to other monoclonal antibodies or known\r\n             hypersensitivity to the study intervention or its excipients.\r\n\r\n          -  Known current drug or alcohol abuse\r\n\r\n          -  Major surgical procedures  28 days prior to the first dose of study intervention, or\r\n             minor surgical procedures 7 days prior to the first dose of study intervention\r\n\r\n          -  Pregnant or lactating\r\n\r\n          -  Any of the following cardiac diseases currently or within the last 6 months:\r\n\r\n               -  QT interval corrected using Fridericia's formula >450 milliseconds in men and >\r\n                  470 milliseconds in women (up to 480 milliseconds may be allowed after discussion\r\n                  between the Investigator and the Medical Monitor).\r\n\r\n               -  Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated\r\n                  acquisition (MUGA) scan or echocardiogram (ECHO)\r\n\r\n               -  Unstable angina pectoris\r\n\r\n               -  Congestive heart failure (New York Heart Association  Grade 2)\r\n\r\n               -  Acute myocardial infarction\r\n\r\n               -  Clinically significant conduction abnormality not controlled with pacemaker or\r\n                  medication\r\n\r\n               -  Significant ventricular or supraventricular arrhythmias (Participants with\r\n                  chronic rate-controlled atrial fibrillation in the absence of other cardiac\r\n                  abnormalities are eligible.)\r\n\r\n          -  Underlying medical conditions that, in the opinion of the investigator and/or medical\r\n             monitor, will render the administration of study drug hazardous or obscure the\r\n             interpretation of safety or efficacy results\r\n      ","sponsor":"Sorrento Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Peripheral T Cell Lymphoma|Diffuse Large B Cell Lymphoma|Biliary Tract Cancer|Extranodal NK T Cell Lymphoma, Nasal","interventions":[{"intervention_type":"Biological","name":"Biological: STI-3031","description":"anti-PD-L1 antibody"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate","time_frame":"Approximately 24 months","description":"Percentage of participants achieving a Complete Response (CR) or Partial Response (PR) at any time during the study as assessed by an Independent Response Committee (IRC) per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Objective Response Rate by treating physician","time_frame":"Approximately 24 months","description":"Percentage of participants achieving a CR or PR at any time during the study as assessed by the Investigator per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of Response","time_frame":"Approximately 24 months","description":"Time from the first documentation of response (CR or PR) to the first documentation of progressive disease (PD) as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Complete Response Rate","time_frame":"Approximately 24 months","description":"Percentage of participants achieving a CR at any time during the study as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of Complete Response Rate","time_frame":"Approximately 24 months","description":"Time from the first documentation of CR to the first documentation of PD as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Progressive-free survival","time_frame":"Approximately 24 months","description":"Time from enrollment until PD or death as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"12-month Progressive-free survival","time_frame":"Approximately 30 months (18 months for enrollment plus 12 months follow-up for the last participant enrolled)","description":"Percentage of participants without PD or death at 12 months after their first dose of study intervention as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Event free survival","time_frame":"Approximately 24 months","description":"Time from enrollment to PD, death, or start of new treatment as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1"},{"outcome_type":"secondary","measure":"Area Under the Curve (AUC) of the blood levels of STI-3031","time_frame":"Approximately 24 months","description":"Measure the actual body exposure to STI-3031"},{"outcome_type":"secondary","measure":"Maximum Plasma Concentration (Cmax) of STI-3031","time_frame":"Approximately 24 months","description":"Measure the maximum (or peak) blood concentration of STI-3031"},{"outcome_type":"secondary","measure":"Time of Maximum concentration observed (Tmax) of STI-3031","time_frame":"Approximately 24 months","description":"Measure the is the time at which the maximum blood concentration of STI-3031 is observed"},{"outcome_type":"secondary","measure":"Half-life (t1/2) of STI-3031","time_frame":"Approximately 24 months","description":"Measure the time it takes for the concentration of the drug in the blood to be reduced by 50%"},{"outcome_type":"secondary","measure":"Immunogenicity","time_frame":"Approximately 24 months","description":"Incidence of anti-drug antibody (ADA) (serum titers of anti-STI-3031 antibodies) and correlation with exposure and activity"},{"outcome_type":"secondary","measure":"Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of STI-3031","time_frame":"Approximately 24 months","description":"Terms, frequency, severity and seriousness of adverse events (AEs) and relationship of AEs to STI-3031 the actual body exposure to drug after administration"}]}
{"nct_id":"NCT05037279","start_date":"2022-01-01","phase":"Phase 3","enrollment":540,"brief_title":"Evaluating Safety and Efficacy of Verity-BCG in BCG-nave Patients With Intermediate and High-risk Non-muscle Invasive Bladder (NMIBC)","official_title":"A Multicenter, Randomized, Double-blind, Controlled Phase III Non-inferiority Study Assessing Efficacy and Safety of VERITY-BCG in Management of Intermediate and High-risk Non-muscle Invasive Bladder Cancer (NMIBC) in BCG-nave Patients.","primary_completion_date":"2025-07-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-08-30","last_update":"2021-09-09","description":"The aim of this study is to evaluate the effect of Verity-BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) and to compare our findings to the standard of care BCG formulation, OncoTICE (BCG) in order to examine our hypothesis that Verity-BCG is at least non-inferior to OncoTICE in achieving 24-month Recurrence Free Survival in NMIBC patients who are at high risk of recurrence and have never been treated with intradermal or intravesical BCG before, with the exception of tuberculosis vaccination in childhood.","other_id":"VRT-BCG-01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Male or Female\r\n\r\n          -  18 years and older\r\n\r\n          -  Low or high-grade NMIBC as defined by 2004 World Health Organization\r\n             (WHO)/International Society of Urological Pathology (ISUP) classification and Grade 2\r\n             or 3 in the 1973 classification, diagnosed within 60 days of registration.\r\n\r\n          -  Pathologically confirmed and completely resected stage Ta or T1 urothelial cell\r\n             carcinoma, with or without associated carcinoma in situ (CIS), diagnosed within 60\r\n             days of registration.\r\n\r\n               1. Patients with T1 disease must have imaging demonstrating no evidence of\r\n                  metastatic disease (based on MRI or CT scan) within 90 days of registration, to\r\n                  confirm stage T1N0M0 disease.\r\n\r\n               2. For patients with stage T1 disease, repeat TURBT must be performed as per\r\n                  standard of care/CUA guidelines.\r\n\r\n          -  Patients may have intermediate or high recurrence risk disease, as indicated by the\r\n             probability of 2-year recurrence of  50% based on the EORTC Bladder Cancer risk\r\n             calculator.\r\n\r\n          -  ECOG performance status of 0-2\r\n\r\n          -  Adequate organ and marrow function as defined below:\r\n\r\n               -  leukocytes 3,000/mcL\r\n\r\n               -  absolute neutrophil count 1,500/mcL\r\n\r\n               -  platelets 100,000/mcL\r\n\r\n               -  total bilirubin  1.5  institutional upper limit of normal (ULN)\r\n\r\n               -  AST(SGOT)/ALT(SGPT) 3  institutional ULN\r\n\r\n               -  creatinine  institutional ULN OR glomerular filtration rate (GFR) 50\r\n                  mL/min/1.73 m2 unless data exists supporting safe use of BCG at lower kidney\r\n                  function values, no lower than 30 mL/min/1.73 m2\r\n\r\n          -  For women of childbearing potential involved in any sexual intercourse that could lead\r\n             to pregnancy: Negative pregnancy test and willingness to use contraceptive (consistent\r\n             with local regulations) during 120 days after the last dose of the study treatment.\r\n             Note: The use of contraceptive methods does not apply to subjects who are abstinent\r\n             for at least 4 weeks before Day 1 and will continue to be abstinent from\r\n             penile-vaginal intercourse 120 days after last dose of study drug treatment. The\r\n             reliability of sexual abstinence needs to be evaluated in relation to the duration of\r\n             the clinical trial and the preferred and usual lifestyle of the participant.\r\n\r\n          -  Note: A woman of non-childbearing potential is defined as follows:\r\n\r\n               -  Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or\r\n                  bilateral salpingectomy);\r\n\r\n               -  Has had a cessation of menses for at least 12 months without an alternative\r\n                  medical cause, and a follicle-stimulating hormone (FSH) test confirming\r\n                  nonchildbearing potential (refer to laboratory reference ranges for confirmatory\r\n                  levels).\r\n\r\n          -  Male patients with female partner of childbearing potential must agree to be abstinent\r\n             or practice an effective method of contraception.\r\n\r\n        Male patients must agree to refrain from donating sperm during the treatment period and for\r\n        at least 120 days after the last dose of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Presence of urothelial carcinoma involving the upper urinary tract or prostatic\r\n             urethra documented by radiological imaging or biopsy, performed within 12 months of\r\n             the start of treatment. Should the imaging or biopsy be performed outside the window\r\n             it will be up to the physicians' discretion to re-scan/biopsy. This is considered T4\r\n             disease.\r\n\r\n          -  CIS only disease.\r\n\r\n          -  Pure squamous cell carcinoma or adenocarcinoma.\r\n\r\n          -  Presence of micropapillary components.\r\n\r\n          -  Other prior non-bladder malignancy, except for the following:\r\n\r\n               -  adequately treated basal cell or squamous cell skin cancer.\r\n\r\n               -  in situ cervical cancer.\r\n\r\n               -  adequately treated stage I or II cancer currently in complete remission, or any\r\n                  other cancer from which the patient has been disease free for five years.\r\n\r\n               -  patients with localized prostate cancer who are being followed by an active\r\n                  surveillance program are also eligible.\r\n\r\n          -  Prior intravesical BCG or intradermal BCG, with the exception of tuberculosis\r\n             vaccination in childhood.\r\n\r\n          -  Chronic administration of steroids (>10 mg prednisone) at the time of randomization.\r\n\r\n          -  Current or planned concomitant biologic therapy, radiation therapy, hormonal therapy,\r\n             chemotherapy, surgery, or other cancer therapy while on study.\r\n\r\n          -  Prior chemoradiation treatment (trimodal therapy or \"TMT\") for bladder cancer.\r\n\r\n          -  Currently being treated or scheduled to have treatment with any systemic or\r\n             intravesical chemotherapeutic agent during the study.\r\n\r\n          -  Receiving any other investigational agents.\r\n\r\n          -  The presence of an impaired immune response irrespective of whether this impairment is\r\n             congenital or caused by disease, drugs or other therapy.\r\n\r\n          -  Known positive HIV serology.\r\n\r\n          -  Presence of a urinary tract infection; treatment should be withheld until urine\r\n             culture is negative and antibiotic therapy is stopped.\r\n\r\n          -  Trauma to the urinary bladder. In case of gross hematuria, therapy should be stopped\r\n             or postponed until the hematuria has been successfully treated or has resolved.\r\n\r\n          -  History of allergic reactions attributed to compounds of similar chemical or biologic\r\n             composition to BCG vaccine.\r\n\r\n          -  Uncontrolled intercurrent illness.\r\n\r\n          -  Psychiatric illness/social situations that would limit compliance with study\r\n             requirements.\r\n\r\n          -  Pregnancy: pregnant women are excluded from this study because VERITY-BCG is an agent\r\n             with the potential for teratogenic or abortifacient effects. Because there is an\r\n             unknown but potential risk for adverse events in nursing infants secondary to\r\n             treatment of the mother with VERITY-BCG, breastfeeding should be discontinued if the\r\n             mother is treated with VERITY-BCG.\r\n      ","sponsor":"Verity Pharmaceuticals Inc.","sponsor_type":"Industry","conditions":"Bladder Cancer|Neoplasm Recurrence|Bladder Cancer Recurrent|Urothelial Carcinoma Bladder|Urothelial Carcinoma Recurrent|Non-Invasive Bladder Urothelial Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Bacillus Calmette-Guerin: Strain Russian BCG-I","description":"Induction: 80 mg weekly for 6 weeks.\r\nMaintenance for intermediate AUA risk patients will be for 3 weeks at 3, 6, and 12 months.\r\nMaintenance for high AUA risk patients will be for 3 weeks at 3, 6, 12, 18, 24, 30 and 36 months."},{"intervention_type":"Drug","name":"Drug: Bacillus Calmette-Guerin: Strain TICE","description":"Induction: 50 mg weekly for 6 weeks.\r\nMaintenance for intermediate AUA risk patients will be for 3 weeks at 3, 6, and 12 months.\r\nMaintenance for high AUA risk patients will be for 3 weeks at 3, 6, 12, 18, 24, 30 and 36 months."}],"outcomes":[{"outcome_type":"primary","measure":"Recurrence Free Survival (RFS) at 24 months","time_frame":"24 months","description":"Cumulative Recurrence Free Survival (RFS) at 24 months following 1st intravesical instillation as estimated using the Kaplan - Meier estimator of the survival function.\r\nRecurrence will be defined as the reappearance of any of the NMIBC tumors as confirmed by cystoscopic biopsy or TURBT."},{"outcome_type":"secondary","measure":"Recurrence Free Survival (RFS)","time_frame":"36 months","description":"Cumulative Recurrence Free Survival (RFS) at 36 months following 1st intravesical instillation as estimated using the Kaplan - Meier estimator of the survival function."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"24 months","description":"Progression Free Survival (PFS) at 24 months as estimated using the Kaplan - Meier estimator of the survival function."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"36 months","description":"Progression Free Survival (PFS) at 36 months as estimated using the Kaplan - Meier estimator of the survival function."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"36 months","description":"Overall Survival (OS) at 36 months as estimated using the Kaplan - Meier estimator of the survival function."},{"outcome_type":"secondary","measure":"Change in Quality of Life","time_frame":"36 months","description":"Change in Quality of Life as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire for NMIBC (EORTC-QLQ-NMIBC24) over 36 months.\r\nThe EORTC QLQ-NMIBC24 is a 24-item self-administered questionnaire that measures health-related quality of life in patients with intermediate to high-risk NMIBC. Items are ranked by the patient from 1 to 4 indicating the extent to which they have experienced those symptoms or problems. 1 = Not at All, 2 = A little, 3=Quite a bit, 4 = Very Much.\r\n- High Score is equivalent to more problems, except for items on sexual function and sexual enjoyment for which a high score is interpreted as better function."},{"outcome_type":"secondary","measure":"Change in functioning and symptom status","time_frame":"36 months","description":"Change in functioning and symptom status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire for Cancer Patients (EORTC-QLQ-C30) over 36 months.\r\nThe EORTC QLQ-C30 consists of 30 items and measures Health Related Quality of Life as well as presence of symptoms across all cancer types. The QLQ-C30 includes nine multi-item scales:\r\n5 functional scales (physical, role, cognitive, emotional, and social)\r\n3 symptom scales (fatigue, pain, and nausea and vomiting);\r\nA global health and quality-of-life scale*\r\nSeveral single-item symptom measures\r\n28 Items are ranked 1 to 4. 1 = Not at All, 2 = A little, 3=Quite a bit, 4 = Very Much.\r\n*2 items are ranked 1 to 7. 1=Very Poor, 7 = Excellent.\r\nHigh score = More symptoms or worse problems\r\n*High Score = Better overall health or Quality of life."},{"outcome_type":"other","measure":"Safety: Incidence of treatment-emergent AEs and SAEs","time_frame":"36 months","description":"Incidence of treatment-emergent AEs and SAEs defined according to the CTCAE v5.0;"},{"outcome_type":"other","measure":"Safety: Number of discontinued subjects","time_frame":"36","description":"Number of subjects discontinuing study drug due to AEs"},{"outcome_type":"other","measure":"Safety: concomitant medications","time_frame":"36 months","description":"Usage of concomitant medications over time."}]}
{"nct_id":"NCT03613181","start_date":"2021-12-31","phase":"Phase 3","enrollment":150,"brief_title":"ANG1005 in Leptomeningeal Disease From Breast Cancer","official_title":"A Randomized Open-Label, Multi-Center Pivotal Study of ANG1005 Compared With Physician's Best Choice in HER2-Negative Breast Cancer Patients With Newly Diagnosed Leptomeningeal Carcinomatosis and Previously Treated Brain Metastases (ANGLeD)","primary_completion_date":"2023-06-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-03-31","last_update":"2021-09-10","description":"This is an open-label Phase 3 study to see if ANG1005 can prolong survival compared to a Physician Best Choice control in HER2-negative breast cancer patients with newly diagnosed leptomeningeal disease and previously treated brain metastases.","other_id":"ANG1005-CLN-07","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"1:1 randomization to experimental arm and comparator arm","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1.  18 years old\r\n\r\n          2. HER2-negative breast cancer\r\n\r\n          3. At least 2 months of expected survival\r\n\r\n          4. Newly diagnosed leptomeningeal carcinomatosis\r\n\r\n          5. Documented history of brain metastasis that has been previously treated with radiation\r\n             therapy\r\n\r\n          6. Neurologically stable\r\n\r\n          7. Eastern Cooperative Oncology Group performance status grade 2\r\n\r\n          8. Adequate laboratory test results prior to first dose\r\n\r\n          9. Patients who are fertile must agree to remain abstinent or use reliable method of\r\n             birth control\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Any prior treatment for leptomeningeal carcinomatosis, except emergency radiotherapy\r\n             or shunt\r\n\r\n          2. Prior treatment with ANG1005\r\n\r\n          3. Patients who have not had radiotherapy for their brain metastases\r\n\r\n          4. Evidence of symptomatic intracranial hemorrhage or increased intracranial pressure\r\n\r\n          5. Patients for whom intrathecal therapy is the most appropriate therapy for\r\n             leptomeningeal disease\r\n\r\n          6. Pregnancy or lactation and patients planning to be pregnant during the study\r\n\r\n          7. Peripheral neuropathy > Grade 2\r\n\r\n          8. Evidence of severe or uncontrolled diseases\r\n\r\n          9. Presence of an infection including abscess or fistulae, or known infection with\r\n             hepatitis B or C or HIV\r\n\r\n         10. History of interstitial lung disease\r\n\r\n         11. Severe conduction disturbance\r\n\r\n         12. Central nervous system disease requiring immediate neurosurgical intervention\r\n\r\n         13. Known allergy to paclitaxel or any of its components\r\n\r\n         14. Contra-indication for contrast-enhanced MRI\r\n      ","sponsor":"Angiochem Inc","sponsor_type":"Industry","conditions":"Leptomeningeal Carcinomatosis|Leptomeningeal Metastases|Brain Metastases|HER2-negative Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ANG1005","description":"Investigational drug"},{"intervention_type":"Drug","name":"Drug: Physician's Best Choice","description":"Active Comparator: one of 3 pre-determined choices of therapies: capecitabine or eribulin or high-dose IV methotrexate."}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival","time_frame":"From the date of randomization until death due to any cause, assessed for up to 2 years."},{"outcome_type":"secondary","measure":"Central nervous system progression-free survival","time_frame":"From the date of randomization until central nervous system progression, assessed for up to 2 years."},{"outcome_type":"secondary","measure":"Central nervous system clinical benefit rate at 3, 6 and 12 months","time_frame":"At 3, 6 and 12 months."},{"outcome_type":"secondary","measure":"6-month and 12-month overall survival rates","time_frame":"At 6 and 12 months."},{"outcome_type":"secondary","measure":"Leptomeningeal carcinomatosis response rate","time_frame":"Assessed for up to 2 years from first patient randomised."},{"outcome_type":"secondary","measure":"Duration of leptomeningeal carcinomatosis response","time_frame":"Assessed for up to 2 years from first patient randomised."},{"outcome_type":"secondary","measure":"Overall survival in triple negative breast cancer patients","time_frame":"From the date of randomization until death due to any cause, assessed for up to 2 years."}]}
{"nct_id":"NCT04928846","start_date":"2021-12-10","phase":"Phase 3","enrollment":600,"brief_title":"A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)","official_title":"A Phase 3 Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Versus Docetaxel in Subjects With Previously Treated c-Met+, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer","primary_completion_date":"2027-03-09","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-03-09","last_update":"2021-06-16","description":"Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-small cell lung cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to determine if telisotuzumab vedotin works better than docetaxel and to assess how safe telisotuzumab vedotin is in adult participants with NSCLC who have previously been treated. Change in disease activity and adverse events will be assessed. Telisotuzumab vedotin is an investigational drug being developed for the treatment of NSCLC. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives intravenous (IV) infusion of telisotuzumab vedotin or IV infusion of docetaxel. Approximately 600 adult participants with c-Met+ NSCLC will be enrolled in the study in approximately 250 sites worldwide. Participants will receive IV telisotuzumab vedotin every 2 weeks or docetaxel every 3 weeks until meeting study drug discontinuation criteria. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.","other_id":"M18-868","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participants must have c-Met overexpression (c-Met+) non-small cell lung cancer\r\n             (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory.\r\n\r\n          -  Archival or fresh tumor material must be submitted for assessment of c-Met levels\r\n             during the Pre-Screening period.\r\n\r\n          -  A histologically documented non-squamous cell NSCLC that is locally advanced or\r\n             metastatic.\r\n\r\n          -  A known epidermal growth factor receptor (EGFR) activating mutation status.\r\n\r\n          -  Actionable alterations in genes other than EGFR .\r\n\r\n          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version\r\n             1.1.\r\n\r\n          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.\r\n\r\n          -  Have received no more than 1 line of prior systemic cytotoxic chemotherapy in the\r\n             locally advanced or metastatic setting.\r\n\r\n               -  Neoadjuvant and adjuvant systemic cytotoxic chemotherapy will count as a prior\r\n                  line for eligibility purposes if progression occurred within 6 months of the end\r\n                  of therapy.\r\n\r\n          -  Have progressed on at least 1 line of prior therapy for locally advanced/metastatic\r\n             NSCLC:\r\n\r\n               -  Participants WITH an actionable gene alteration (e.g., anaplastic lymphoma kinase\r\n                  [ALK] translocation): must have progressed on (or be considered ineligible for)\r\n                  anti-cancer therapy targeting driver gene alterations and systemic cytotoxic\r\n                  chemotherapy.\r\n\r\n               -  Participants WITHOUT an actionable gene alteration: must have progressed on (or\r\n                  be considered ineligible for) systemic cytotoxic chemotherapy and immune\r\n                  checkpoint inhibitor (as monotherapy or in combination with chemotherapy).\r\n\r\n          -  Participants with metastases to the central nervous system (CNS) are eligible only\r\n             after definitive therapy (such as surgery or radiotherapy) is provided and:\r\n\r\n               -  There is no evidence of progression of CNS metastases at least 4 weeks after\r\n                  definitive therapy.\r\n\r\n               -  They are asymptomatic and off or on a stable or reducing dose of systemic\r\n                  steroids and/or anticonvulsants for at least 2 weeks prior to first dose of\r\n                  telisotuzumab vedotin.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participants with adenosquamous histology.\r\n\r\n          -  Actionable epidermal growth factor receptor (EGFR) activating mutations.\r\n\r\n          -  Participants who have received prior c-Met-targeted antibodies.\r\n\r\n          -  A history of other malignancies except:\r\n\r\n               -  Malignancy treated with curative intent and with no known active disease present\r\n                  for 2 years before the first dose of study drug and felt to be at low risk for\r\n                  recurrence by investigator.\r\n\r\n               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence\r\n                  of disease.\r\n\r\n               -  Adequately treated carcinoma in situ without current evidence of disease.\r\n\r\n          -  A history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis\r\n             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of\r\n             active pneumonitis on screening chest computed tomography (CT) scan. A history of\r\n             prior radiation pneumonitis in the radiation field (fibrosis) is permitted.\r\n\r\n          -  Unresolved clinically significant adverse event (AE) >= Grade 2 from prior anticancer\r\n             therapy, except for alopecia or anemia.\r\n\r\n          -  Major surgery within 21 days prior to the first dose of telisotuzumab vedotin.\r\n\r\n          -  Clinically significant condition(s) as listed in the protocol.\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Telisotuzumab Vedotin","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"IV Infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-Free Survival (PFS)","time_frame":"Up to approximately 39 months","description":"PFS is defined as the time from randomization to the first occurrence of radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) per Independent Central Review (ICR) or death from any cause."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 58.25 months","description":"OS is defined as the time from randomization to the event of death from any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to approximately 58.25 months","description":"ORR is defined as the percentage of subjects with a complete response (CR) or partial response (PR) based on RECIST v1.1, per ICR."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Up to approximately 58.25 months","description":"DoR is defined for responders as the time from response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause per ICR."},{"outcome_type":"secondary","measure":"Time to Deterioration in Cough, Pain or Dyspnea as measured by the Cough, Pain and Dyspnea items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13)","time_frame":"Up to approximately 58.25 months","description":"The EORTC QLQ-LC13 is the lung cancer specific module of the core EORTC QLQ-C30. The QLQ-LC13 includes 13 questions that include both multi-item and single-item scales of lung cancer-associated symptoms (e.g., pain, coughing, hemoptysis, and dyspnea) and side-effects from chemo- and radiotherapy (e.g., hair loss, neuropathy, sore mouth and dysphagia). All scale and item scores are linearly transformed to a 0 to 100 scale, with higher scores representing increasing symptom levels or impacts."},{"outcome_type":"secondary","measure":"Time to Deterioration of Physical Functioning as measured by the Physical Functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30).","time_frame":"Up to approximately 58.25 months","description":"The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden."},{"outcome_type":"secondary","measure":"Change from Baseline in Quality of Life as measured by the Global Health Status/Quality of Life Domain of the EORTC QLQ-C30.","time_frame":"Up to approximately 58.25 months","description":"The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden."}]}
{"nct_id":"NCT04889989","start_date":"2021-12-01","phase":"N/A","enrollment":120,"brief_title":"Microwave Ablation in Chinese Patients With Lung Tumors","official_title":"A Single-Arm, Prospective, Multicenter Study to Evaluate the Effectiveness and Safety of the NeuWave Certus Microwave Ablation System in Chinese Patients With Primary or Secondary Tumors in the Lung","primary_completion_date":"2024-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-12-31","last_update":"2021-09-16","description":"Adult patients with non-small cell lung cancer (NSCLC) or oligometastatic lung tumors will all receive microwave ablation (MWA) performed percutaneously by doctors who are experienced in lung tumor ablation. 120 patients will participate across 8 clinical study sites all in China.","other_id":"NEU_2020_02","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Single-arm, prospective, multicenter clinical trial with a performance goal","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Signed the informed consent form and willing to fulfill the study-related assessments\r\n             and procedure schedule.\r\n\r\n          2. Lung tumor patients  18 years of age who are ineligible for/decline surgery and who\r\n             plan to receive microwave ablation therapy.\r\n\r\n          3. ECOG performance status score of 0-2.\r\n\r\n          4. Patients with stages IA1-IA2 NSCLC with documented results from a biopsy or patients\r\n             with clinically diagnosed oligometastatic lung tumor.\r\n\r\n          5. Tumor(s) to be ablated in a single surgery should be a maximum of one NSCLC tumor or a\r\n             maximum of three ipsilateral oligometastatic lung tumors.\r\n\r\n          6. Tumor(s) to be ablated in a single surgery should be  2cm, locate in the outer\r\n             two-thirds of a lung, not closer than 1 cm from the hilum of lung, great vessels,\r\n             principal bronchus, trachea or esophagus, and not contiguous with the pleura.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Pregnant or breast-feeding.\r\n\r\n          2. Patients with implantable pacemakers or other electronic implants.\r\n\r\n          3. Oligometastatic tumors patients whose primary lesion cannot be controlled or have\r\n             widely metastases, in the opinion of the investigator and/or treating oncologist.\r\n\r\n          4. Any planned concurrent procedure at the time of ablation.\r\n\r\n          5. Planned treatment for other tumors in the same side lung during the study period.\r\n\r\n          6. With a skin infection or ulceration at the site to be punctured by probe(s).\r\n\r\n          7. Clinical or imaging findings consistent with an active pulmonary infection.\r\n\r\n          8. Patients with severe pulmonary fibrosis in the area intended to ablate, especially\r\n             drug-induced pulmonary fibrosis.\r\n\r\n          9. Patients with prior radiotherapy in the area intended to ablate.\r\n\r\n         10. Patients with uncontrolled malignant pleural effusion at the lung side with tumor to\r\n             ablate.\r\n\r\n         11. Tumors where the anticipated zone of ablation would encompass significant (in the\r\n             opinion of the treating physician) emphysematous or bullous disease.\r\n\r\n         12. The investigator anticipates that the ablation zone of the multiple tumor(s) to be\r\n             ablated may have overlapping ablation zones.\r\n\r\n         13. Patients who have received lung ablation or surgical resection therapy within 30 days\r\n             prior to the ablation procedure under study and those who plan to receive lung tumor\r\n             ablation or surgical resection therapy or radiation therapy on the ablated lung side\r\n             before completing the primary efficacy endpoint assessment approximately 30 days after\r\n             the ablation procedure.\r\n\r\n         14. Patients who received systemic therapy such as chemotherapy, targeted drug therapy, or\r\n             immunotherapy within 7 days prior to the ablation procedure under study, and patients\r\n             who had a systemic treatment plan such as chemotherapy, targeted drug therapy,\r\n             immunotherapy, etc. before completing the primary efficacy endpoint assessment\r\n             approximately 30 days after the ablation procedure.\r\n\r\n         15. Patients with uncorrectable coagulopathy based on investigator judgment.\r\n\r\n         16. Patients with a platelet count  50  109/L.\r\n\r\n         17. Patients who cannot discontinue antiplatelet medication (e.g., aspirin, clopidogrel,\r\n             prasugrel, ticagrelor) at least 5 days before the ablation procedure through 24 hours\r\n             post-procedure.\r\n\r\n         18. Patients who cannot discontinue anticoagulant medication (e.g., rivaroxaban, apixaban,\r\n             dabigatran, edoxaban) at least 3 days before the ablation procedure through 24 hours\r\n             post-procedure.\r\n\r\n         19. Patients who cannot discontinue warfarin before at least 5 days before the ablation\r\n             procedure of the study or have an INR > 1.5.\r\n\r\n         20. As judged by the investigator, the patient has hypertension that cannot be effectively\r\n             controlled by pharmacological treatments.\r\n\r\n         21. Severe hepatic, renal, cardiac, pulmonary or cerebral insufficiency, severe anemia,\r\n             dehydration, and severe nutrition and metabolism disorders, which cannot be corrected\r\n             or improved within a short term; or serious systemic infection; or severe\r\n             neuromuscular diseases.\r\n\r\n         22. Expected survival less than 6 months.\r\n\r\n         23. Participation in any other interventional clinical study within 30 days before\r\n             screening.\r\n\r\n         24. Physical or psychological condition which would impair study participation.\r\n\r\n         25. Patient is judged unsuitable for study participation by the investigator for any other\r\n             reason.\r\n\r\n             Intra-Ablation Exclusion Criteria:\r\n\r\n         26. Before ablation probe puncture on the skin, patient is judged unsuitable for study\r\n             participation due to intolerance to anesthesia.\r\n\r\n         27. Before ablation probe puncture on the skin, patient is judged unsuitable for study\r\n             participation due to presenting any other condition.\r\n      ","sponsor":"Ethicon, Inc.","sponsor_type":"Industry","conditions":"Cancer of the Lung","interventions":[{"intervention_type":"Device","name":"Device: Microwave Ablation","description":"Percutaneous microwave ablation using the NeuWave Microwave Ablation System for non-small cell lung cancer or oligometastatic lung tumors"}],"outcomes":[{"outcome_type":"primary","measure":"Technical Efficacy Rate","time_frame":"30 days (+/- 7) post-ablation","description":"Percentage of tumors that are completely covered by the ablation zone with no sign of pathological enhancement according to the lung contrast-enhanced CT assessment"},{"outcome_type":"secondary","measure":"Technical Success Rate","time_frame":"Ablation Day (day 0)","description":"Percentage of tumors that achieve A0 or A1 ablation classification determinations (i.e., complete tumor ablation with a surrounding margin) in the lung CT immediately following the initial ablation procedure"},{"outcome_type":"secondary","measure":"Local Tumor Progression","time_frame":"1 year post-ablation","description":"Local tumor progression and time to local tumor progression of any original-ablated tumor(s)"},{"outcome_type":"secondary","measure":"Progression-Free Survival","time_frame":"1 year post-ablation","description":"Length of time the patient is still alive after the original ablation procedure and with no evidence of any tumor progression (local, regional, or distant)"},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"1 year post-ablation","description":"Length of time the patient is still alive after the original ablation procedure within the study duration"}]}
{"nct_id":"NCT04603807","start_date":"2021-11-30","phase":"Phase 3","enrollment":220,"brief_title":"A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases","official_title":"Randomized, Open Label, Multicenter, Phase III Study of Entrectinib Versus Crizotinib in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring ROS1 Gene Rearrangements With and Without Central Nervous System Metastases","primary_completion_date":"2027-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-11-30","last_update":"2021-09-21","description":"The study will compare the efficacy and safety of entrectinib with crizotinib in participants with advanced or metastatic ROS1 non-small cell lung cancer (NSCLC). The participants will self-administer oral entrectinib or crizotinib as described in the protocol and local prescribing information. Treatments will continue until progressive disease, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.","other_id":"MO41552","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically-confirmed diagnosis of advanced or recurrent (Stage\r\n             IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors\r\n             a documented ROS1 gene rearrangement.\r\n\r\n          -  No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other\r\n             systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical\r\n             treatment) or metastatic (Stage IV) NSCLC\r\n\r\n          -  Prior radiotherapy is allowed if more than 14 days have elapsed between the end of\r\n             treatment and randomization\r\n\r\n          -  Measurable systemic disease according to RECIST v1.1\r\n\r\n          -  Participants with measurable and non-measurable CNS lesions per RECIST v1.1, including\r\n             leptomeningeal carcinomatosis\r\n\r\n          -  Life expectancy of at least 12 weeks\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2\r\n\r\n          -  Adequate hematologic, renal, liver functions\r\n\r\n          -  Participants must have recovered from effects of any major surgery or significant\r\n             traumatic injury at least 28 days before the first dose of study treatment\r\n\r\n          -  Ability to swallow entrectinib and crizotinib intact without chewing, crushing, or\r\n             opening the capsules\r\n\r\n          -  For women of childbearing potential: agreement to remain abstinent (refrain from\r\n             heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per\r\n             year during the treatment period and for up to 5 weeks after the last dose of\r\n             entrectinib or for at least 90 days after the last dose of crizotinib\r\n\r\n          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use\r\n             contraceptive measures, and agreement to refrain from donating sperm.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic\r\n             therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or\r\n             metastatic (Stage IV) NSCLC\r\n\r\n          -  NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excluding\r\n             alopecia, fatigue, nausea and lack of appetite), which have not shown improvement and\r\n             are strictly considered to interfere with current study drug\r\n\r\n          -  History of recent (within the past 3 months) symptomatic congestive heart failure or\r\n             ejection fraction  50% observed during screening for the study\r\n\r\n          -  History of prolonged corrected QTc interval\r\n\r\n          -  Peripheral sensory neuropathy  Grade 2\r\n\r\n          -  Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase\r\n             inhibitor-induced pneumonitis\r\n\r\n          -  Previous malignancy within the past 3 years\r\n\r\n          -  Incomplete recovery from any surgery prior to the start of study treatment\r\n\r\n          -  Active GI disease (e.g., Crohn's disease, ulcerative colitis or short gut syndrome) or\r\n             other malabsorption syndrome that would reasonably impact drug absorption\r\n\r\n          -  History of prior therapy-induced pneumonitis\r\n\r\n          -  Any condition (in the past 3 months) e.g., myocardial infarction, unstable angina,\r\n             coronary/peripheral artery bypass graft, cerebrovascular accident or transient\r\n             ischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmias\r\n             requiring medication\r\n\r\n          -  Known active infections (bacterial, fungal or viral, including human immunodeficiency\r\n             virus positive)\r\n\r\n          -  History of hypersensitivity to any of the additives in the entrectinib and/or\r\n             crizotinib drug formulations\r\n\r\n          -  Pregnant or lactating women\r\n\r\n          -  Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency\r\n             syndrome (AIDS)-related illness\r\n\r\n          -  Any clinically significant concomitant disease or condition that could interfere with,\r\n             or for which the treatment might interfere with, the conduct of the study or the\r\n             absorption of oral medications.\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Carcinoma, Non-Small-Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: Entrectinib","description":"Entrectinib will be self-administered orally at a dose of 600 mg (three 200 mg capsules per day) once daily with or without food."},{"intervention_type":"Drug","name":"Drug: Crizotinib","description":"Crizotinib will be self-administered orally at a dose of 250 mg twice daily with or without food."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) in participants with central nervous system (CNS) metastases at baseline","time_frame":"Up to 7 years","description":"PFS is defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause whichever occurs first determined by a blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)."},{"outcome_type":"secondary","measure":"Progression-free survival in the Central Nervous System (CNS-PFS)","time_frame":"Up to 7 Years","description":"CNS-PFS is defined as the time from randomization to the first documented disease progression in the CNS or death from any cause, whichever occurs first, as determined by the BIRC using RECIST v1.1"},{"outcome_type":"secondary","measure":"Overall response rate (ORR)","time_frame":"Up to 7 Years","description":"ORR is defined as the percentage of participants who attain Complete Response (CR) or Partial Response (PR) as assessed by the BIRC and the investigator per RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"Up to 7 Years","description":"DOR is defined as the time from when response (CR or PR) is first documented to disease progression or death, whichever occurs first, as assessed by the BIRC and the investigator per RECIST v1.1"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"Up to 7 years","description":"PFS is defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause, whichever occurs first, as determined by the BICR and investigator using RECIST v1.1"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 7 Years","description":"OS is defined as the time from randomization to death from any cause"},{"outcome_type":"secondary","measure":"Percentage of participants with confirmed deterioration as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)","time_frame":"Up to 7 Years"},{"outcome_type":"secondary","measure":"Percentage of participants with impact on lung cancer-specific symptoms assessed by the EORTC QLQ-LC13","time_frame":"Up to 7 Years"},{"outcome_type":"secondary","measure":"Objective response rate in the CNS-ORR in participants with CNS metastases at baseline","time_frame":"Up to 7 Years","description":"CNS-ORR is defined as the percentage of participants who attain CR or PR for lesions in the CNS, as determined by the BIRC per RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response in the CNS (CNS-DOR) in participants with CNS metastases at baseline","time_frame":"Up to 7 Years","description":"CNS-DOR is defined as the time from when a CNS response (CR or PR) is first documented to disease progression in the CNS, as determined by the BIRC per RECIST v1.1"},{"outcome_type":"secondary","measure":"Percentage of participants with Adverse Events and Serious Adverse Events and Adverse Events leading to dose modifications/interruptions, study drug withdrawal or death","time_frame":"Up to 7 Years","description":"Assessed by the investigator according to the NCI CTCAE v5.0"},{"outcome_type":"other","measure":"Change in the scores of EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L)","time_frame":"Up to 7 Years","description":"To evaluate health status utility scores of participants to inform pharmacoeconomic modeling using the EuroQol 5-Dimension Questionnaire (5-level version; EQ-5D-5L) index-based and visual analog scale (VAS) scores"}]}
{"nct_id":"NCT04988295","start_date":"2021-11-17","phase":"Phase 3","enrollment":500,"brief_title":"A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure","official_title":"A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure","primary_completion_date":"2023-05-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-11-30","last_update":"2021-09-17","description":"The purpose of this study is to assess the efficacy of lazertinib, amivantamab, carboplatin, and pemetrexed (LACP) compared with carboplatin and pemetrexed (CP), in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure.","other_id":"CR109061","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participant must have at least 1 measurable lesion, according to Response Evaluation\r\n             Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated\r\n\r\n          -  Participant must have histologically or cytologically confirmed, locally advanced or\r\n             metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after\r\n             the tine of locally advanced metastatic disease diagnosis by either epidermal growth\r\n             factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation\r\n\r\n          -  A participant with definitively, locally treated brain metastases must be clinically\r\n             stable and asymptomatic, with or without low-dose corticosteroid treatment (less than\r\n             or equal to [<=]10 milligrams [mg]) prednisone or equivalent), for at least 14 days\r\n             prior to randomization\r\n\r\n          -  Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1\r\n\r\n          -  Any toxicities from prior systemic anticancer therapy must have resolved to National\r\n             Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version\r\n             5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral\r\n             neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)\r\n\r\n          -  A woman of childbearing potential must have a negative serum pregnancy test at\r\n             screening and within 72 hours of the first dose of study treatment and must agree to\r\n             further serum or urine pregnancy tests during the study\r\n\r\n          -  Participant must have progressed on or after osimertinib monotherapy as the most\r\n             recent line of treatment. Osimertinib must have been administered as either the\r\n             first-line treatment for locally advanced or metastatic disease or in the second- line\r\n             setting after prior treatment with first- or second-generation EGFR tyrosine kinase\r\n             inhibitor (TKI). Participants who received either neoadjuvant and/or adjuvant\r\n             treatment are eligible if progression to locally advanced or metastatic disease\r\n             occurred at least 12 months after the last dose of such therapy and then the\r\n             participant progressed on or after osimertinib in the locally advanced or metastatic\r\n             setting. Treatment with osimertinib must be discontinued at least 8 days (4\r\n             half-lives) prior to randomization (that is last dose no later than Day -8)\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participant received radiotherapy for palliative treatment of NSCLC less than 14 days\r\n             prior to randomization\r\n\r\n          -  Participant has active brain metastases not definitively treated with local therapy\r\n\r\n          -  Participant has leptomeningeal disease, or participant has spinal cord compression not\r\n             definitively treated with surgery or radiation\r\n\r\n          -  Participant has known small cell transformation\r\n\r\n          -  Participant has a medical history of interstitial lung disease (ILD), including\r\n             drug-induced ILD or radiation pneumonitis\r\n      ","sponsor":"Janssen Research & Development, LLC","sponsor_type":"Industry","conditions":"Carcinoma, Non-Small-Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: Lazertinib","description":"Lazertinib will be administered orally."},{"intervention_type":"Drug","name":"Drug: Amivantamab","description":"Amivantamab will be administered as an IV infusion."},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Pemetrexed will be administered as an IV infusion."},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Carboplatin will be administered as an IV infusion."}],"outcomes":[{"outcome_type":"secondary","measure":"Intracranial PFS","time_frame":"Up to 17 months","description":"Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1."},{"outcome_type":"primary","measure":"Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to 17 months","description":"PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Objective Response as Assessed by BICR","time_frame":"Up to 17 months","description":"Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to 48 months","description":"Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Up to 17 months","description":"DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR."},{"outcome_type":"secondary","measure":"Time to Subsequent Therapy (TTST)","time_frame":"Up to 17 months","description":"TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first."},{"outcome_type":"secondary","measure":"Progression-Free Survival After First Subsequent Therapy (PFS2)","time_frame":"Up to 17 months","description":"PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first."},{"outcome_type":"secondary","measure":"Time to Symptomatic Progression (TTSP)","time_frame":"Up to 17 months","description":"TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms."},{"outcome_type":"secondary","measure":"Number of Participants with Adverse Events (AEs)","time_frame":"Up to 48 months","description":"An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study."},{"outcome_type":"secondary","measure":"Number of Participants with Clinical Laboratory Abnormalities","time_frame":"Up to 48 months","description":"Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported."},{"outcome_type":"secondary","measure":"Serum Concentration of Amivantamab","time_frame":"Up to 17 months","description":"Serum samples will be analyzed to determine concentrations of amivantamab."},{"outcome_type":"secondary","measure":"Plasma Concentration of Lazertinib","time_frame":"Up to 17 months","description":"Plasma samples will be analyzed to determine concentrations of lazertinib."},{"outcome_type":"secondary","measure":"Number of Participants with Anti-Amivantamab Antibodies","time_frame":"Up to 17 months","description":"Number of participants with anti-amivantamab antibodies will be reported."},{"outcome_type":"secondary","measure":"Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)","time_frame":"Up to 17 months","description":"NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology."},{"outcome_type":"secondary","measure":"European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score","time_frame":"Up to 17 months","description":"The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms."},{"outcome_type":"secondary","measure":"Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)","time_frame":"Up to 17 months","description":"PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures."}]}
{"nct_id":"NCT04976647","start_date":"2021-11-10","phase":"Phase 2","enrollment":156,"brief_title":"A Randomized, Open-Label, Multicenter, Phase II Study of HLX07 (Anti-EGFR Antibody) In Combination With HLX10 (Anti-PD-1 Antibody) With or Without Chemotherapy Versus HLX10 With Chemotherapy in First Line Recurrent or Metastatic Squamous Non-Small Cell Lung Cancer","official_title":"A Randomized, Open-Label, Multicenter, Phase II Study of HLX07 (Anti-EGFR Antibody) In Combination With HLX10 (Anti-PD-1 Antibody) With or Without Chemotherapy Versus HLX10 With Chemotherapy in First Line Recurrent or Metastatic Squamous Non-Small Cell Lung Cancer","primary_completion_date":"2023-01-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-10-30","last_update":"2021-07-26","description":"The purpose of this study is to evaluate the clinical efficacy and safety of HLX07 In Combination with HLX10 with or without Chemotherapy versus HLX10 with Chemotherapy in First Line Recurrent or Metastatic Squamous Non-Small Cell Lung Cancer.This study consists of three periods, screening period (28 days), treatment period and follow-up period (including safety follow-up, survival follow-up).Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria.","other_id":"HLX10HLX07-sqNSCLC-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed diagnosis of previously untreated, Recurrent or Metastatic\r\n             Squamous Non-Small Cell Lung Cancer\r\n\r\n          -  EGFR immunohistochemistry (IHC) H score 200 assessed by central lab\r\n\r\n          -  Has measurable disease as defined by RECIST 1.1 as determined by the IRRC\r\n\r\n          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)\r\n             Performance Scale\r\n\r\n          -  Has a life expectancy of greater than 12 weeks\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Histologically non-squamous NSCLC must be exclused. For non-small-cell histology, if\r\n             has squamous components be allowed\r\n\r\n          -  Has history of such as PD-1/PD-L1EGFR CTLA4 targeted therapy\r\n\r\n          -  EGFR sensitivity mutation or ALK or ROS1 gene rearrangement need to be excluded\r\n\r\n          -  Has had other active malignancies within 5 years or at the same time\r\n\r\n          -  Has uncontrolled pleural effusionpericardial effusion or ascites\r\n      ","sponsor":"Shanghai Henlius Biotech","sponsor_type":"Industry","conditions":"Squamous Non-small-cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: HLX10+chemo","description":"HLX10 300mg IV Q3W; carboplaitin (AUC5 or 6) IV Q3W + nab-paclitaxel (260mg/m2) IV Q3W for 4-6 circle"},{"intervention_type":"Drug","name":"Drug: HLX10+HLX07+chemo","description":"HLX07 1500mg IV q3w; HLX10 300mg IV Q3W; carboplaitin (AUC5 or 6) IV Q3W + nab-paclitaxel (260mg/m2) IV Q3W for 4-6 circle"},{"intervention_type":"Drug","name":"Drug: HLX10+HLX07","description":"HLX07 1500mg IV q3w; HLX10 300mg IV Q3W;"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per RECIST 1.1 assessed by IRRC","time_frame":"Up to 5 years","description":"ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by IRRC. ORR will be determined for each treatment arm."},{"outcome_type":"primary","measure":"Progression Free Survival (PFS) per RECIST 1.1 assessed by IRRC(Independent Radiology Review Committee)","time_frame":"Up to 5 years","description":"PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by IRRC or death due to any cause, whichever occurs first. PFS will be determined for each treatment arm"},{"outcome_type":"secondary","measure":"Adverse Events (AE)","time_frame":"Up to 5 years","description":"An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported for each treatment arm."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 assessed by IRRC","time_frame":"Up to 5 years","description":"For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR will be determined for each treatment arm"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to 5 years","description":"OS is defined as the time from randomization to death due to any cause. OS will be determined for each treatment arm."}]}
{"nct_id":"NCT04037241","start_date":"2021-11-01","phase":"Phase 2/Phase 3","enrollment":167,"brief_title":"Study of Anti-CEA CAR-T + Chemotherapy VS Chemotherapy Alone in Patients With CEA+Pancreatic Cancer & Liver Metastases","official_title":"A Randomized Open-Label Phase 2b Study of Hepatic Infusions of Anti-CEA CAR-T Cells Alternating With Systemic Chemotherapy Versus Chemotherapy Alone In Patients With Liver Metastases Due To CEA-Expressing Pancreatic Adenocarcinoma","primary_completion_date":"2022-01-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2022-01-01","last_update":"2020-07-15","description":"This study is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy alone in patients with CEA-expressing pancreatic adenocarcinoma with liver metastases.","other_id":"STI-CEA-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients must have documented CEA-expressing pancreatic adenocarcinoma with\r\n             unresectable liver metastases. Documentation of CEA-expressing adenocarcinoma may be\r\n             demonstrated by an elevated serum CEA level ( 10 ng/mL) or by the detection of CEA on\r\n             the cell surface of adenocarcino3.\r\n\r\n          -  Documentation of disease progression of pancreatic adenocarcinoma following the\r\n             initiation of first-line treatment with FOLFIRINOX or gemcitabine-based therapy.ma\r\n             cells by immunohistochemistry (IHC).\r\n\r\n          -  The primary pancreatic tumor may be intact and limited lung metastases ( 3 lesions,\r\n             none > 1 cm in longest diameter) and lymphoid metastases ( 3 lesions, none > 1 cm in\r\n             longest diameter) are permitted.\r\n\r\n          -  There must be at least one measurable metastatic liver lesion (  10 mm in longest\r\n             diameter).\r\n\r\n          -  ECOG performance status of 0 or 1.\r\n\r\n          -  Be willing and able to comply with the study schedule and all other protocol\r\n             requirements.\r\n\r\n          -  Females of childbearing potential must have 2 negative pregnancy tests prior to the\r\n             start of study treatment, and must agree to pregnancy tests during the study; sexually\r\n             active female and male patients must be willing to use an effective birth control to\r\n             avoid pregnancy.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Received anti-cancer chemotherapy or investigational systemic anti-cancer treatments\r\n             other than first line FOLFIRINOX or gemcitabine-based chemotherapy for advanced\r\n             pancreatic adenocarcinoma.\r\n\r\n          -  Received FOLFIRINOX or gemcitabine-based therapy within 14 days before receiving the\r\n             first dose of study treatment.\r\n\r\n          -  Have any unresolved toxicity > Grade 1 from previous anticancer therapy, except for\r\n             stable chronic toxicities ( Grade 2) that are not expected to resolve.\r\n\r\n          -  Have a history of histologically confirmed metastases outside the liver, lungs, or\r\n             lymph nodes.\r\n\r\n          -  More than 50% replacement of one or both hepatic lobes with tumor.\r\n\r\n          -  Tumor causing biliary obstruction not amenable to stenting.\r\n\r\n          -  Received prior anti-CEA agents, CAR-T, CAR-T cell line, CAR-NK, CAR-pNK, or CAR-NK\r\n             cell line therapies.\r\n\r\n          -  Have any clinically significant low baseline lab results for hemoglobin, platelet\r\n             counts, or neutrophil counts at screening.\r\n\r\n          -  Has any untreated or ongoing intra-abdominal infection or bowel obstruction.\r\n\r\n          -  Has any clinically significant elevated baseline lab results for serum creatinine,\r\n             aspartate aminotransferase (AST), and total bilirubin (except for patients in whom\r\n             hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at\r\n             screening.\r\n\r\n          -  Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of\r\n             chronic hepatitis B or C.\r\n\r\n          -  Female patients who are pregnant or breastfeeding.\r\n\r\n          -  Has active bacterial, viral or fungal infections.\r\n\r\n          -  Has any significant medical condition, laboratory abnormality, or psychiatric illness\r\n             that would prevent the patient from participating in the study.\r\n\r\n          -  Has any condition, including the presence of laboratory abnormalities that places the\r\n             patient at an unacceptable risk if the patient was to participate in the study.\r\n\r\n          -  Are receiving medications that are strong inducers CYP3A4 or CYP2C8 within 2 weeks of\r\n             initiating treatment in the Bridging Therapy Period (rifampicin, carbamazepine,\r\n             phenytoin, efavirenz, nevirapine, rifabutin, rifapentine, St. John's wort).\r\n\r\n          -  Are receiving medications that inhibit CYP3A4 or CYP2C8 within 1 week of initiating\r\n             treatment in the Bridging Therapy Period (ketoconazole and other imidazole\r\n             antifungals, erythromycin, clarithromycin, itraconazole, voriconazole, fluoxetine,\r\n             gemfibrozil, cimetidine, lopinavir, nefazodone, telaprevir, ritonavir, saquinavir,\r\n             indinavir, or nelfinavir).\r\n\r\n          -  Are receiving medications that inhibit UGT1A1 within 1 week of initiating\r\n             nanoliposomal irinotecan therapy (atazanavir, gemfibrozil, indinavir).\r\n\r\n          -  Left ventricular ejection fraction (LVEF) < 40%\r\n      ","sponsor":"Sorrento Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Malignant Tumor of Pancreas Metastatic to Liver","interventions":[{"intervention_type":"Biological","name":"Biological: Anti-CEA CAR-T cells","description":"Doses will be delivered by hepatic arterial infusions using a pressure enabled drug delivery (PEDD) device"},{"intervention_type":"Drug","name":"Drug: gemcitabine/nab paclitaxel","description":"systemic chemotherapy regimen"},{"intervention_type":"Drug","name":"Drug: NLIR+FU/FA","description":"systemic chemotherapy regimen"},{"intervention_type":"Drug","name":"Drug: Capecitabine","description":"systemic chemotherapy regimen"}],"outcomes":[{"outcome_type":"other","measure":"Assess the persistence of CAR-T cells in liver tumor biopsies over time.","time_frame":"6 - 12 months","description":"As an exploratory analysis, the engraftment of CAR-T cells in planned liver tumor biopsies will be analyzed to assess persistence of CAR-T cells during the Treatment and Observation Periods of the study."},{"outcome_type":"primary","measure":"Assess efficacy by overall survival","time_frame":"6 - 12 months","description":"As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable."},{"outcome_type":"secondary","measure":"Assess safety by monitoring adverse events","time_frame":"6 - 12 months","description":"As a measure of safety, the types, frequencies, and severities of adverse events and their relationship to study drug will be summarized."},{"outcome_type":"secondary","measure":"Assess efficacy by within-liver progression free survival (PFS)","time_frame":"6 - 12 months","description":"As a measure of activity, within-liver PFS will be assessed. The events for the assessment of within-liver PFS will be measured from the date of randomization to the date of disease progression within the liver or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate."},{"outcome_type":"secondary","measure":"Assess efficacy by progression free survival (PFS)","time_frame":"6 - 12 months","description":"As a measure of activity, PFS will be assessed. The events for the assessment of PFS will be measured from the date of randomization to the date of disease progression or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate."},{"outcome_type":"secondary","measure":"Assess efficacy by within-liver time to progression (TTP)","time_frame":"6 - 12 months","description":"As a measure of activity, within-liver TTP will be assessed. The events for the assessment of within-liver TTP will be measured from the date of randomization to the date of disease progression within the liver. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate."},{"outcome_type":"secondary","measure":"Assess efficacy by time to progression (TTP)","time_frame":"6 - 12 months","description":"As a measure of activity, TTP will be assessed. The events for the assessment of TTP will be measured from the date of randomization to the date of disease progression. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate."},{"outcome_type":"secondary","measure":"Assess efficacy by within-liver radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)","time_frame":"6 - 12 months","description":"As a measure of activity, overall response rate within-liver will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Assess efficacy by overall whole-body radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)","time_frame":"6 - 12 months","description":"As a measure of activity, overall response rate for overall whole-body will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Assess efficacy by duration of response within-liver in accordance with RECIST v 1.1 criteria","time_frame":"6 - 12 months","description":"As a measure of activity, duration of response within-liver will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Assess efficacy by duration of response of overall whole-body in accordance with RECIST v 1.1 criteria","time_frame":"6 - 12 months","description":"As a measure of activity, duration of response of overall whole-body will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Assess efficacy by serologic response rates by CEA levels","time_frame":"6 - 12 months","description":"As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Assess efficacy by serologic response rates by CA 19-9 levels","time_frame":"6 - 12 months","description":"As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol."},{"outcome_type":"secondary","measure":"Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)","time_frame":"6 - 12 months","description":"As a measure of quality-of-life, the EORTC QLQ-C30 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study."},{"outcome_type":"secondary","measure":"Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)","time_frame":"6 - 12 months","description":"As a measure of quality-of-life specific for patients with pancreatic cancer, the EORTC QLQ-PAN26 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study."},{"outcome_type":"secondary","measure":"Evaluation of Quality-of-Life using the 5-level EQ-5D version (EQ-5D-5L) questionnaire","time_frame":"6 - 12 months","description":"As a measure of quality-of-life, the EQ-5D-5L questionnaire will be administered at months 2, 4, 6 of the Treatment Period and at the end of study."},{"outcome_type":"other","measure":"Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions","time_frame":"6 - 12 months","description":"As an exploratory analysis, serum cytokine levels (pg/mL) will be measured over time by a standard laboratory test using Enzyme-linked immunosorbent assay (ELISA) to determine if increases in cytokines predict response and/or toxicity to liver arterial infusions."},{"outcome_type":"other","measure":"Assess if neutrophil: lymphocyte ratio (NLR) correlate with response from hepatic arterial infusions","time_frame":"6 - 12 months","description":"As an exploratory analysis, NLR will be calculated to determine if there is a correlation with response and/or toxicity."}]}
{"nct_id":"NCT05043402","start_date":"2021-11-01","phase":"Phase 3","enrollment":400,"brief_title":"A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer","official_title":"An Open Label Randomized Study of Navicixizumab Plus Paclitaxel and Navicixizumab Monotherapy in Comparison to Paclitaxel Monotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer","primary_completion_date":"2023-11-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-08-15","last_update":"2021-09-20","description":"This is a Phase 3, randomized, open-label, 2-stage, multicenter study of navicixizumab with or without paclitaxel compared with paclitaxel monotherapy in patients with platinum-resistant advanced epithelial ovarian cancer and specific biomarkers, as measured by the proprietary and validated Xerna TME Panel biomarker assay. Eligible patients must have received at least 2 prior regimens but not more than 5 prior regimens, including treatment with a monoclonal antibody angiogenesis inhibitor (e.g., bevacizumab), must be considered platinum-resistant, and must be considered appropriate to receive single-agent paclitaxel chemotherapy as a next line of therapy. All patients must be willing and able to provide a formalin-fixed paraffin embedded (FFPE) archive or core tumor sample collected during screening for classification as B+ or B- biomarker status based on RNA expression data from the Xerna TME Panel biomarker assay. The co-primary efficacy endpoints are ORR by RECIST v1.1 and PFS (as assessed by blinded independent radiological review [BIRR]) analyzed at different timepoints. Analysis of the ORR primary efficacy endpoints will occur at the end of Stage 1 and at the end of Stage 2; the PFS primary efficacy endpoint will be analyzed at the end of Stage 2.","other_id":"ONCX-NAV-G301","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patient must have epithelial ovarian, fallopian tube, or primary peritoneal cancer\r\n\r\n          -  Patients must have received 2 and not more than 5 prior therapies, including at least\r\n             1 line of therapy containing bevacizumab (or biosimilar).\r\n\r\n          -  Patients must be considered platinum-resistant, defined as progression within 6 months\r\n             from completion of a platinum-containing therapy\r\n\r\n          -  Patient must be considered appropriate for treatment with weekly paclitaxel\r\n             monotherapy as the next line of therapy.\r\n\r\n          -  Patient must be willing and able to provide an FFPE archival or core tumor sample for\r\n             determination of biomarker status on the Xerna TME Panel biomarker assay (positive or\r\n             negative) prior to study treatment.\r\n\r\n          -  Presence of at least one measurable lesion, as defined by RECIST v1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ\r\n             function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Non-epithelial ovarian carcinoma.\r\n\r\n          -  Ovarian tumors with low malignant potential (i.e., borderline tumors).\r\n\r\n          -  Primary platinum-refractory disease (defined as progression during or within 4 weeks\r\n             after completion of the first platinum regimen).\r\n\r\n          -  Patient has received an anti-angiogenic product other than bevacizumab or biosimilar.\r\n\r\n          -  Patient has congestive heart failure\r\n\r\n          -  Patient has a history of myocardial infarction, cerebral vascular accident, or\r\n             transient ischemic attacks within 6 months\r\n\r\n          -  Patient has a history of cardiac ischemia or heart failure within 6 months\r\n\r\n          -  Baseline B-type natriuretic peptide (BNP) value >100 pg/mL or N-terminal-proBNP\r\n             (NT-proBNP) value of > 125 pg/mL.\r\n\r\n          -  LVEF <50%.\r\n\r\n          -  Peak tricuspid velocity >3.0 m/s on Doppler ECHO.\r\n\r\n          -  Clinically significant ECG abnormality, as assessed by the investigator\r\n\r\n          -  Blood pressure (BP) >140/90 mmHg\r\n\r\n          -  History of bowel obstruction, including sub-occlusive disease, related to the\r\n             underlying disease\r\n\r\n          -  Hemoptysis >2.5 mL within 8 weeks prior\r\n\r\n          -  Major surgical procedure, or significant traumatic injury within 28 days\r\n\r\n          -  Uncontrolled seizure disorder or active neurologic disease\r\n\r\n          -  Patients with a cardiac aneurysm.\r\n      ","sponsor":"OncXerna Theraputics, Inc.","sponsor_type":"Industry","conditions":"Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: navicixizumab","description":"navicixizumab IV"},{"intervention_type":"Device","name":"Device: Xerna TME Panel","description":"RNA-seq-based biomarker platform that classifies any given patient tumor sample into phenotypes based on the dominant biology of the tumor microenvironment (TME)."}],"outcomes":[{"outcome_type":"primary","measure":"ORR","time_frame":"Up to 2 years","description":"Overall Response Rate defined as the proportion of patients with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)"},{"outcome_type":"primary","measure":"PFS","time_frame":"Up to 2 years","description":"Progression Free Survival"},{"outcome_type":"secondary","measure":"OS","time_frame":"Up to 2 years","description":"Overall Survival"},{"outcome_type":"secondary","measure":"TTR","time_frame":"Up to 2 years","description":"Time to response"},{"outcome_type":"secondary","measure":"DCR","time_frame":"Up to 2 years","description":"Disease control rate defined as the proportion of patients with stable disease (SD) or a confirmed BOR of CR or PR"},{"outcome_type":"secondary","measure":"DOR","time_frame":"Up to 2 years","description":"Duration of Response"}]}
{"nct_id":"NCT05047991","start_date":"2021-10-31","phase":"Phase 2","enrollment":153,"brief_title":"Study of Irinotecan Liposome Injection-containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma","official_title":"A Multicenter, Randomized, Open-lable, Parallel-controlled, Phase II Study to Evaluate the Differences of Safety and Efficacy of Irinotecan Liposome Injection-containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma","primary_completion_date":"2023-11-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-11-30","last_update":"2021-09-17","description":"This is a multicenter, randomized, open-lable, parallel-controlled phase II study of irinotecan liposome injection-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma. The purpose of this study is to evaluate the differences of safety and efficacy of irinotecan liposome injection-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma.","other_id":"HE072-CSP-004","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":70,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Age 18 to 70 years old (inclusive), regardless of gender;\r\n\r\n          2. Histologically or cytologically confirmed unresectable, locally advanced, or\r\n             metastatic pancreatic adenocarcinoma;\r\n\r\n          3. At least one measurable lesion according to RECIST 1.1.\r\n\r\n          4. No prior systemic anti-tumor therapy, except those with disease progression more than\r\n             6 months after adjuvant therapy or neoadjuvant therapy;\r\n\r\n          5. Patients with prior local treatment (radical radiotherapy or radical\r\n             chemoradiotherapy, etc.) may be enrolled provided that the local treatment does not\r\n             involve the target lesion, or the target lesion is within the treatment area, but the\r\n             size has increased more than 20% since the post-treatment evaluation, and also must be\r\n             completed at least 4 weeks before the first administration of the study drug,\r\n             palliative decompensated radiotherapy (such as bone metastases) must be completed at\r\n             least 2 weeks before the first administration of the study drug;\r\n\r\n          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1;\r\n\r\n          7. Life expectancy >3 months;\r\n\r\n          8. Adverse reactions must recover to grade 1 or baseline according to CTCAE 5.0 (except\r\n             for toxicity such as alopecia, grade 2 or less sensory neuropathy, etc., which have\r\n             been judged no safety risk by investigators).\r\n\r\n          9. Patients should not receive cell growth factors or blood and platelet transfusion\r\n             within 7 days before the initiate administration of study drug, and laboratory test\r\n             must meet the following criteria:\r\n\r\n             neutrophile count 1.510^9/L; platelet count 10010^9/L; hemoglobin 90 g/L or 5.6\r\n             mmol/L; serum creatinine 1ULN or creatinine clearance rate must be  50 mL/min when\r\n             serum creatinine >1.0ULN; total bilirubin 1.5ULN; aspartate aminotransferase (AST)\r\n             and alanine aminotransferase (ALT) 2.5ULN or 5ULN if intrahepatic lesions exist;\r\n             Albumin 3 g/dL.\r\n\r\n         10. Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR) and\r\n             prothrombin time (PT) 1.5  ULN for patients not receiving therapeutic\r\n             anticoagulation.\r\n\r\n         11. According to the related guidelines, patients with HBV DNA or HBsAg and/or anti-HBC\r\n             positive must receive prophylactic treatment (at least one week before the initial\r\n             administration of the study drug) and take antiviral drugs in stable dose (e.g.,\r\n             entecavir, tenofovir, or lamivudine; No adefovir or interferon are allowed) at study\r\n             entry with planned monitoring and management, including baseline HBV DNA levels.\r\n             Patient receiving active hepatitis C virus (HCV) treatment must use astable dose of\r\n             drugs at study entry and be subject to planned monitoring and management according to\r\n             antiviral drug guidelines;\r\n\r\n         12. Female patients with reproductive potential must agree to use adequate contraception\r\n             from the signing of informed consent to at least 6 months after the study completion\r\n             and have a negative serum pregnancy test within 3 days before enrollment, and must be\r\n             non-lactating. Male patients must agree to use medically approved contraception during\r\n             the study period and for 6 months after the study completion;\r\n\r\n         13. Ability to understand and the willingness to sign a written informed consent.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Patients with acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary tumor\r\n             and pancreatic neuroendocrine tumor;\r\n\r\n          2. Patients with definitive diagnosis of CNS metastasis;\r\n\r\n          3. Patients with hepatic encephalopathy at screening;\r\n\r\n          4. Patients with clinically symptomatic ascites requiring puncture or drainage or who\r\n             have received ascites drainage within the past 3 months, except for those with only a\r\n             small amount of ascites on imaging but no clinical symptoms;\r\n\r\n          5. Uncontrolled third lacunar effusion other than ascites (e.g., large pleural or\r\n             pericardial effusion) within 4 weeks before the first administration of the test drug;\r\n\r\n          6. Previous malignancies in the past five years (except radically resected and\r\n             non-recurring basal cell carcinoma of the skin, squamous cell carcinoma of the skin,\r\n             superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of\r\n             cervical, or other carcinoma in situ);\r\n\r\n          7. Patients with partial or complete biliary obstruction who has not relieved by active\r\n             treatment;\r\n\r\n          8. History of serious cardiovascular disease, including but not limited to:\r\n\r\n        1) Acute myocardial infarction, unstable angina pectoris, coronary angioplasty, stroke,\r\n        severe pulmonary embolism; 2) New York Heart Association class grade III or IV congestive\r\n        heart failure or left ventricular ejection fraction (LVEF) < 50%; 3) Poorly controlled\r\n        hypertension (systolic blood pressure  150 mmHg and/or diastolic blood pressure 95 mmHg)\r\n        with optimal treatment; 4) Ventricular arrhythmia; 5) Patients with prolonged QT/QTc\r\n        interval in baseline electrocardiogram (ECG) (QTcF > 480 ms, Fridericia formula: QTcF =\r\n        QT/(RR^0.33), RR = 60/heart rate); 6) Patients with clinically significant abnormal\r\n        electrocardiogram (ECG) according to the investigator's assessment.\r\n\r\n        9.Patients with uncontrolled active bleeding.\r\n\r\n        10.Patients with known interstitial lung disease;\r\n\r\n        11.Patients with known peripheral neuropathy (CTCAE grade 3 or 4);\r\n\r\n        12.Patients with severe lung, liver, kidney, endocrine, immune system, skin or\r\n        musculoskeletal diseases within 3 months prior to the first dose and who are not suitable\r\n        for enrollment in the opinion of the investigator;\r\n\r\n        13.Patients who are at risk of active infection or have active infection that may affect\r\n        the results of the study (such as severe pneumonia requiring hospitalization, bacteremia,\r\n        acute bacterial infection, infectious complications, tuberculosis, active HIV infection,\r\n        etc.) or who, in the judgment of the investigator, are not suitable for participation in\r\n        this clinical trial. Active hepatitis B virus is defined as HBV DNA10^4 copies or  2000\r\n        IU/mL; active hepatitis C virus or active HIV infection is defined as HCV-RNA positive;\r\n\r\n        14.Gastrointestinal diseases of clinical significance, such as bleeding, inflammation,\r\n        obstruction, >grade 1 diarrhea, malabsorption syndrome, diseases significantly affecting\r\n        gastrointestinal function, gastric or small bowel resection, etc;\r\n\r\n        15.Patients with known to have dihydropyrimidine dehydrogenase (low activity) or\r\n        deficiency;\r\n\r\n        16.Patients with definite Gilbert syndrome;\r\n\r\n        17.History of explicit neurological or psychiatric disorders, including epilepsy or\r\n        dementia;\r\n\r\n        18.Patients with known alcohol or drug dependence.\r\n\r\n        19.Patients who have concomitant use of strong CYP3A4 inducers within 2 weeks prior to the\r\n        first dose, or strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week prior to\r\n        the first dose;\r\n\r\n        20.Patients who have required systemic glucocorticoids (prednisone >10 mg/day or equivalent\r\n        dose of the similar drugs) or other immunosuppressive agents within 14 days before the\r\n        first dose of the study drug. Except for treatment with local, ocular, intra-articular,\r\n        intranasal, and inhaled glucocorticoids in the absence of active autoimmune disease,\r\n        short-term preventive treatment with glucocorticoids (e.g., prevention of contrast\r\n        allergy);\r\n\r\n        21.Patients who have major organ surgery (except for needle biopsy, central venous\r\n        catheterization, port-cath, stenting to relieve biliary obstruction, and percutaneous\r\n        hepatic biliary drainage, cholecystostomy) or selective operation plan were performed\r\n        within 4 weeks before the first dose of the study drug;\r\n\r\n        22.Patients with known allergy to irinotecan liposome injection, other liposome products,\r\n        oxaliplatin, 5-fluorouracil, leucovorin, Nab-paclitaxel, other albumin products,\r\n        gemcitabine or any of the ingredients in the above products.;\r\n\r\n        23. Patients who are not suitable for this study as determined by the investigator.\r\n      ","sponsor":"CSPC Ouyi Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Pancreatic Cancer Non-resectable|Pancreatic Cancer Metastatic","interventions":[{"intervention_type":"Drug","name":"Drug: Irinotecan Liposome Injection","description":"Irinotecan Liposome Injection, intravenously, over 90 min on day 1and day 15 of every 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Fluorouracil","description":"5-Fluorouracil (5-Fu), intravenously, over 46 h on day 1 and day 15 of every 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Leucovorin","description":"Leucovorin (LV), intravenously, over 30 min on day 1 and day 15 of every 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Oxaliplatin","description":"Oxaliplatin, intravenously, over 2 h on day 1 and day 15 of every 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Nab paclitaxel","description":"Paclitaxel (albumin bound), intravenously, over 30 min on day 1, day 8 and day 15 of every 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Gemcitabine, intravenously, over 30 min on day 1, day 8 and day 15 of every 28-day cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-Free Survival (PFS)","time_frame":"Up to twelve months after the last patient's first administration","description":"Time from date of the first dose to date of recorded disease progression or death, whichever occurs first."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to twelve months after the last patient's first administration","description":"The percentage of patients who achieve a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to twelve months after the last patient's first administration","description":"Time from date of the first dose to date of death from any cause."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Up to twelve months after the last patient's first administration","description":"The percentage of patients who achieve a CR, PR or stable disease (SD) based on the RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to twelve months after the last patient's first administration","description":"Time from first documented response (CR or PR whichever occurs first, based on investigator's assessment per RECIST 1.1) to date of disease progression or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)","time_frame":"Up to twelve months after the last patient's first administration","description":"The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0."},{"outcome_type":"secondary","measure":"Peak Plasma Concentration","time_frame":"Day 0 to Day 7 of circle 1","description":"Cmax"},{"outcome_type":"secondary","measure":"Area under the plasma concentration versus time curve","time_frame":"Day 0 to Day 7 of circle 1","description":"AUC"},{"outcome_type":"secondary","measure":"UGT1A1","time_frame":"Within 3 days before the first dose","description":"UGT1A1 gene polymorphism"}]}
{"nct_id":"NCT05042375","start_date":"2021-10-31","phase":"Phase 3","enrollment":706,"brief_title":"A Trial of Camrelizumab Combined With Famitinib Malate in Treatment Nave Subjects With PD-L1-Positive Recurrent or Metastatic Non-Small Cell Lung Cancer","official_title":"A Randomized, Open-Label, Controlled, Multi-center Phase  Study of Camrelizumab Combined With Famitinib Malate Versus Pembrolizumab in Treatment Nave Subjects With PD-L1-Positive Recurrent or Metastatic Non-Small Cell Lung Cancer","primary_completion_date":"2024-03-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-05-01","last_update":"2021-09-13","description":"The study is being conducted to evaluate the efficacy, and safety of camrelizumab combined with famitinib malate vs. pembrolizumab in treatment nave subjects with programmed death-ligand 1(PD-L1)-positive recurrent or metastatic non-small cell lung cancer (NSCLC).","other_id":"SHR-1210-III-331","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Camrelizumab Combined with Famitinib Malate versus Pembrolizumab","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Have a histologically or cytologically confirmed diagnosis of metastatic NSCLC (stage\r\n             IV according to the TNM staging criteria [8th edition] published by the International\r\n             Association for the Study of Lung Cancer [IASLC]), or NSCLC that recurs after curable\r\n             surgery, radiotherapy, or radiochemotherapy.\r\n\r\n          2. Have measurable disease based on RECIST v1.1.\r\n\r\n          3. ECOG PS score: 0-1.\r\n\r\n          4. Have a life expectancy of at least 3 months.\r\n\r\n          5. Non-surgically sterilized female subjects or women of childbearing potential must be\r\n             negative for a serum pregnancy test within 3 days prior to the first dose and must be\r\n             non-lactating. Female subjects of childbearing potential and male subjects with\r\n             partners of childbearing potential must agree to take highly effective contraceptive\r\n             measures during the study period and within 6 months after the last dose of study\r\n             drugs.\r\n\r\n          6. Have voluntarily agreed to participate by giving written informed consent for the\r\n             study, have good compliance, and cooperate with follow-up visits.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Accompanied with EGFR activating mutation, ALK fusion gene positive or ROS1 mutation.\r\n\r\n          2. Have uncontrolled clinically symptomatic pleural effusion, pericardial effusion, or\r\n             ascites.\r\n\r\n          3. Have known history of prior malignancy in the past 3 years.\r\n\r\n          4. Have had an allogeneic tissue/solid organ transplant.\r\n\r\n          5. Have active pulmonary tuberculosis.\r\n\r\n          6. Have clinical symptoms of the heart or heart diseases that are not well controlled.\r\n\r\n          7. Have hypertension which cannot be well controlled by antihypertensives\r\n\r\n          8. Urinalysis has indicated that the urine protein is  ++ and quantitative test of urine\r\n             protein has confirmed that the 24-h urine protein is > 1.0 g.\r\n\r\n          9. Have a thrombosis tendency or are currently receiving thrombolysis/anticoagulation\r\n             therapy.\r\n\r\n         10. Have received major surgery within 4 weeks prior to randomization; or palliative\r\n             radiotherapy within 2 weeks prior to randomization; or have not recovered from the\r\n             toxicities and/or complications of previous interventions to NCI-CTCAE Grade  1.\r\n\r\n         11. Have known history of arterial/venous thrombosis within 6 months prior to\r\n             randomization, such as cerebrovascular accidents, deep vein thrombosis and pulmonary\r\n             embolism.\r\n\r\n         12. Have received prior therapy with anti-PD-1/PD-L1 monoclonal antibodies, anti-CTLA-4\r\n             monoclonal antibodies, or small molecule VEGFR inhibitors.\r\n\r\n         13. Have known allergies to other monoclonal antibodies or any component of famitinib.\r\n\r\n         14. Are currently participating and receiving study therapy or have participated in a\r\n             study and received the last dose of study drug within 4 weeks (or 5 half-lives of the\r\n             study drug) prior to randomization.\r\n\r\n         15. Have other potential factors that may affect the study results or result in the\r\n             premature discontinuation as determined by the investigator, such as alcoholism, drug\r\n             abuse, substance abuse, other serious diseases (including mental illness) requiring\r\n             concomitant treatment, serious laboratory abnormalities, or family or social factors\r\n             that could affect the safety of medication.\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: camrelizumab + famitinib","description":"Camrelizumab for injection, 200 mg; Famitinib malate capsules, 20 mg."},{"intervention_type":"Drug","name":"Drug: pembrolizumab","description":"pembrolizumab 200 mg."},{"intervention_type":"Drug","name":"Drug: camrelizumab","description":"Camrelizumab for injection, 200 mg."}],"outcomes":[{"outcome_type":"primary","measure":"PFS assessed by BIRC","time_frame":"up to 3 years","description":"Progression-Free-Survival, defined as the time from randomization to the first occurrence of disease progression as determined by IRC with use of RECIST v1.1 or death from any cause, whichever occurs first."},{"outcome_type":"primary","measure":"OS","time_frame":"up to 4 years","description":"OS is the time interval from the date of randomization to death due to any reason or lost of follow-up."},{"outcome_type":"secondary","measure":"PFS assessed by investigator","time_frame":"up to 3 years","description":"Progression-Free-Survival"},{"outcome_type":"secondary","measure":"ORR","time_frame":"up to 3 years","description":"Objective Response Rate, determined using RECIST v1.1 criteria, defined as best overall response (CR or PR) across all assessment time points"},{"outcome_type":"secondary","measure":"DCR","time_frame":"up to 3 years","description":"Disease Control Rate, determined using RECIST v1.1 criteria"},{"outcome_type":"secondary","measure":"DoR","time_frame":"up to 3 years","description":"Duration of Response, determined using RECIST v1.1 criteria"},{"outcome_type":"secondary","measure":"TTF","time_frame":"up to 3 years","description":"Time to Treatment Failure, defined as the time from randomization to treatment discontinuation."},{"outcome_type":"secondary","measure":"AEs+SAEs","time_frame":"from the first drug administration to within 90 days for the last SHR-1210 dose","description":"Adverse Events and Serious Adverse Events"}]}
{"nct_id":"NCT04942054","start_date":"2021-10-31","phase":"Phase 1","enrollment":141,"brief_title":"A Study in Patients With Advanced Breast Cancer","official_title":"A Phase 1 Study to Determine Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of SCO-120 in Hormone Receptor Positive, HER-2 Negative Advanced Breast Cancer Patients","primary_completion_date":"2024-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-01-31","last_update":"2021-07-01","description":"A Phase 1, Open label, Dose escalation and Dose expansion study of SCO-120 in HR +ve HER2-ve advanced/ metastatic breast cancer (MBC) patients to evalaute the safety, tolerability and prelimnary efficacy. Initial part with dose escalation is to determine the MTD and RP2D, and PK and PD characterisation. RP2D will be further evalauted for prelimnary efficacy in MBC patients with tretament failure on Aromatase Inhibitor/Fulvestrant/CDK4-6 inhibitors with or with out ESR1 mutation.","other_id":"SCO-120-19-22","allocation":"N/A","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"This is a 3 X 3 Design, sequential doses of 300 mg, 600 mg, 800 mg, 1200 mg will be studied. Other dose strength will be studied based on results.","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. All 3 parts of Study:\r\n\r\n               -  Male or females, Age 18 years or older\r\n\r\n               -  2. Histologically or cytologically diagnosed with ER+/HER2- adenocarcinoma of the\r\n                  breast cancer with an evidence of metastatic/loco-regionally recurrent\r\n                  disease/unresectable advanced disease not amenable to treatment with curative\r\n                  intent\r\n\r\n               -  3. Not more than 3 prior chemotherapeutic regimens\r\n\r\n               -  4. ECOG performance status 0-1.\r\n\r\n               -  5. Adequate organ and immune system function as indicated by laboratory values\r\n\r\n               -  6. Female subjects must be non-lactating and non-breast feeding\r\n\r\n               -  7. Willing and available to participate for the entire study\r\n\r\n               -  8. Willing and able to comply with protocol requirements\r\n\r\n          2. For Part 1& 2\r\n\r\n               -  Patient must have evaluable disease (according to RECIST 1.1).\r\n\r\n               -  Documented disease progression or resistance to at least 1 prior endocrine\r\n                  therapy (with or without CDK 4/6 therapy).\r\n\r\n          3. For Part 3\r\n\r\n               -  Patient must have measurable lesions (according to RECIST 1.1)\r\n\r\n               -  Part 3a: HR+ve, HER2- MBC patients with ESR1 mutations\r\n\r\n               -  Part 3b: HR+ve HER2- MBC patients resistant to AI therapies\r\n\r\n               -  Part 3c: HR+ve HER2- MBC patients resistant to AI+Fulvestrant+ CDK4/6i\r\n\r\n        Exclusion Criteria:\r\n\r\n        1. All 3 parts of Study:\r\n\r\n          -  Major surgery <4 weeks of C1D1\r\n\r\n          -  Evidence of organ dysfunction or inadequate bone marrow reserve or any clinically\r\n             significant finidngs\r\n\r\n          -  Patients with visceral crisis or impending visceral crisis and rapidly progressing\r\n             disease\r\n\r\n          -  4 Serology tests +ve for HIV, HCV, HBsAg\r\n\r\n          -  H/o any relevant allergy/hypersensitivity/idiosyncrasy to drugs/ chemically related to\r\n             Study drugor its excipients\r\n\r\n          -  Received an IMP within 30 days/5 half life to C1D1\r\n\r\n          -  Known or suspected history of significant drug abuse/Alcohol as judged by the\r\n             Investigator\r\n\r\n          -  Malabsorption syndrome/IBD/other illness that would affect oral absorption of Study\r\n             drug\r\n\r\n          -  Uncontrolled intercurrent illness that would limit compliance with study requirements\r\n             / have impact on endpoints / safety\r\n\r\n          -  10 6 months H/o MI/unstable angina, ongoing > G2 cardiac dysrhythmia, prolonged QTcF/\r\n             uncontrolled AF, coronary/peripheral artery bypass graft, HF of NYHA_Class II or\r\n             greater and CVA (+TIA)\r\n\r\n          -  11 H/o Endometrial intraepithelial neoplasia, other malignancy < 5 yrs prior to\r\n             enrollment\r\n\r\n          -  12. Known active uncontrolled CNS metastases, carcinomatous meningitis, or\r\n             leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or\r\n             progressive growth\r\n\r\n          -  13. Pulmonary lymphangitic metastases\r\n\r\n          -  14. Current abnormal vaginal bleeding or symptomatic endometrial disorders.\r\n\r\n          -  15. For Part 2: Use of other ET that block the estrogen receptor: atleast 8 weeks\r\n             before enrollment (28 weeks for fulvestrant)\r\n\r\n          -  16. For Part 2: Liver-only metastases (are not evaluable by FES-PET/CT imaging)\r\n\r\n          -  17. For Part 3: Prior treatment with other oral SERDs.\r\n      ","sponsor":"Sun Pharma Advanced Research Company Limited","sponsor_type":"Industry","conditions":"HER2-negative Breast Cancer|Advanced Breast Cancer|Hormone Receptor-positive Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Part 2","description":"Pharmacodyanamic (PD) dose exploration cohorts"},{"intervention_type":"Drug","name":"Drug: Part 3","description":"Dose expansion at dose(s)  maximum tolerated dose (MTD) cohort"},{"intervention_type":"Drug","name":"Drug: Part 1","description":"Dose escalation cohort"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of dose limiting toxicities at each dose levels (Part 1 only)","time_frame":"28 Days/End of Cycle 1"},{"outcome_type":"primary","measure":"Incidence and severity of adverse events with each dose level","time_frame":"upto 30 days of last dose","description":"The intensity of adverse events will be graded as per CTCAE, Version 5.0 and categorized as serious adverse events or non-serious adverse events."},{"outcome_type":"secondary","measure":"evaluation of Cmax (Part 1 and Part 2)","time_frame":"Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)","description":"Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations"},{"outcome_type":"secondary","measure":"evaluation of tmax (Part 1 and Part 2)","time_frame":"Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)","description":"Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations"},{"outcome_type":"secondary","measure":"evaluation of AUC (Part 1 and Part 2)","time_frame":"Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)","description":"Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations"},{"outcome_type":"secondary","measure":"tumour response","time_frame":"Every 8 weeks, for 'Time point Response (Partial Response[PR], Stable Disease[SD], Disease progression [DP] or Complete Response [CR]), Through study completion, an average of 1 year."},{"outcome_type":"other","measure":"pharmacodynamic biomarker","time_frame":"At Screening and End of Cycle 1' (Each Cycle of 28 days)","description":"Pharmacodynamic Biomarkers [Estrogen receptor (ER) expression, Ki67 down regulation from Tissue Biopsy, and Estrogen receptor occupancy with [(18)F] Fluoroestradiol Positron Emission Tomography (18F-FES PET) scan]"}]}
{"nct_id":"NCT04908813","start_date":"2021-10-31","phase":"Phase 2","enrollment":150,"brief_title":"Study of HLX22 in Combanition With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy for Treatment of Locally Advanced or Metastatic Gastric Cancer","official_title":"A Randomized, Double-blindedMulticenterPhase II Clinical Study of HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination With Trastuzumab and Chemotherapy (XELOX) Versus Placebo in Combination With Trastuzumab and Chemotherapy (XELOX) for Treatment of Locally Advanced or Metastatic Gastric Cancer (GC)","primary_completion_date":"2023-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-09-30","last_update":"2021-09-17","description":"The purpose of this study is to evaluate the clinical efficacy and safety of HLX22 in the HER2+ Locally Adanved or Metastatic Gastric Cancer as the first-line therapy.This study consists of three periods, screening period (28 days), treatment period and follow-up period (including safety follow-up, survival follow-up).Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria. The enrolled subjects will receive an intravenous infusion of HLX22/placebo and SOC(standard of care: Trastuzumab + XELOX) once every 3 weeks until the loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent or other reasons as specified in the protocol(whichever occurs earlier).","other_id":"HLX22-GC-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of previously untreated, locally\r\n             advanced unresectable or metastatic HER2 positive gastric adenocarcinoma.\r\n\r\n          -  HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination\r\n             with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization\r\n             (FISH), as assessed by central review on primary or metastatic tumor\r\n\r\n          -  Has measurable disease as defined by RECIST 1.1 as determined by the IRRC\r\n\r\n          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)\r\n             Performance Scale\r\n\r\n          -  Has a life expectancy of greater than 6 months\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 2 years\r\n\r\n          -  Has history of HER2 targeted therapy\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the trial, interfere with the participant's\r\n             participation for the full duration of the trial, or is not in the best interest of\r\n             the participant to participate, in the opinion of the treating investigator\r\n\r\n          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the\r\n             projected duration of the trial, starting with the screening visit through 7 months\r\n             after the last dose of trial treatment\r\n      ","sponsor":"Shanghai Henlius Biotech","sponsor_type":"Industry","conditions":"Gastric Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: HLX22","description":"IV Q3W D1"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"IV Q3W D1"},{"intervention_type":"Drug","name":"Drug: Trastuzumab","description":"IV Q3W D1"},{"intervention_type":"Drug","name":"Drug: Oxaliplatin","description":"IV Q3W D1"},{"intervention_type":"Drug","name":"Drug: Capecitabine","description":"PO Q3W D1-D14"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) per RECIST 1.1 assessed by IRRC(Independent Radiology Review Committee)","time_frame":"Up to 5 years","description":"PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by IRRC or death due to any cause, whichever occurs first. PFS will be determined for each treatment arm"},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per RECIST 1.1 assessed by IRRC","time_frame":"Up to 5 years","description":"ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by IRRC. ORR will be determined for each treatment arm."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to 5 years","description":"OS is defined as the time from randomization to death due to any cause. OS will be determined for each treatment arm."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 assessed by IRRC","time_frame":"Up to 5 years","description":"For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR will be determined for each treatment arm"},{"outcome_type":"secondary","measure":"Adverse Events (AE)","time_frame":"Up to 5 years","description":"An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported for each treatment arm."}]}
{"nct_id":"NCT04819100","start_date":"2021-10-31","phase":"Phase 3","enrollment":170,"brief_title":"A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)","official_title":"LIBRETTO-432: A Placebo-controlled Double-Blinded Randomized Phase 3 Study of Adjuvant Selpercatinib Following Definitive Locoregional Treatment in Participants With Stage IB-IIIA RET Fusion-Positive NSCLC","primary_completion_date":"2028-08-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2032-11-30","last_update":"2021-09-21","description":"The reason for this study is to see if the study drug, selpercatinib, compared to placebo is effective and safe in delaying cancer return in participants with early-stage non-small cell lung cancer (NSCLC), who have already had surgery or radiation. Participants who are assigned to placebo and stop the study drug because their disease comes back or gets worse have the option to potentially crossover to selpercatinib. Participation could last up to three years.","other_id":"18126","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Must have histologically confirmed Stage IB, II, or IIIA NSCLC.\r\n\r\n          -  Must have an activating RET gene fusion in tumor based on polymerase chain reaction\r\n             (PCR) or next generation sequencing (NGS).\r\n\r\n          -  Must have received definitive locoregional therapy with curative intent (surgery or\r\n             radiotherapy) for Stage IB, II, or IIIA NSCLC.\r\n\r\n             -- Must have undergone the available anti-cancer therapy (including chemotherapy or\r\n             durvalumab) or not be suitable for it, based on the investigator's discretion.\r\n\r\n          -  Must have completely recovered from definitive therapy (surgery or radiotherapy) as\r\n             well as adjuvant therapy at the time of randomization.\r\n\r\n          -  Maximum time allowed between definitive therapy completion and randomization must be:\r\n\r\n               -  10 weeks if no chemotherapy was administered\r\n\r\n               -  26 weeks if adjuvant chemotherapy was administered\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\r\n\r\n          -  Adequate hematologic, hepatic, and renal function.\r\n\r\n          -  Willingness of men and women of reproductive potential to observe conventional and\r\n             highly effective birth control for the duration of the study and for at least 2 weeks\r\n             after last dose of study drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Additional oncogenic drivers in NSCLC, if known.\r\n\r\n          -  Evidence of small cell lung cancer.\r\n\r\n          -  Clinical or radiologic evidence of disease recurrence or progression following\r\n             definitive therapy.\r\n\r\n          -  Known or suspected interstitial fibrosis or interstitial lung disease or history of\r\n             (noninfectious) pneumonitis that required steroids.\r\n\r\n          -  Clinically significant active cardiovascular disease or history of myocardial\r\n             infarction within six months prior to planned start of selpercatinib or prolongation\r\n             of the QT interval corrected for heart rate using Fridericia's formula (QTcF) greater\r\n             than 470 milliseconds.\r\n\r\n          -  Have known uncontrolled human immunodeficiency virus (HIV)-1/2 infection.\r\n\r\n          -  Have known active hepatitis B or C.\r\n\r\n          -  Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing\r\n             intercurrent illness, such as hypertension or diabetes, despite optimal treatment.\r\n\r\n          -  Major surgery within 4 weeks prior to planned start of selpercatinib.\r\n\r\n          -  Clinically significant active malabsorption syndrome or other condition likely to\r\n             affect gastrointestinal absorption of the study drug.\r\n\r\n          -  Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or\r\n             other in situ cancers or a malignancy diagnosed greater than or equal to two years\r\n             previously and not currently active.\r\n\r\n          -  Pregnancy or lactation.\r\n\r\n          -  Prior treatment with a selective RET inhibitor (e.g. selpercatinib or pralsetinib).\r\n      ","sponsor":"Loxo Oncology, Inc.","sponsor_type":"Industry","conditions":"Carcinoma, Non-Small-Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: Selpercatinib","description":"Administered orally."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Administered orally."}],"outcomes":[{"outcome_type":"primary","measure":"Event-Free Survival (EFS)","time_frame":"Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)","description":"EFS by Investigator Assessment in the Primary Analysis Population"},{"outcome_type":"secondary","measure":"EFS","time_frame":"Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)","description":"EFS by investigator assessment in the overall population"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Randomization to death from any cause (estimated as up to 9 years)]","description":"OS"},{"outcome_type":"secondary","measure":"EFS","time_frame":"Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)]","description":"EFS by blinded independent central review (BICR)"},{"outcome_type":"secondary","measure":"Time to Distant Disease Recurrence in the Central Nervous System (CNS)","time_frame":"Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)","description":"Time to distant disease recurrence in the CNS by investigator assessment and BICR"},{"outcome_type":"secondary","measure":"Progression Free Survival on the Next Line of Treatment (PFS2)","time_frame":"Randomization to disease progression on the next line of treatment or death from any cause (estimated as up to 9 years)","description":"PFS2 by investigator assessment"},{"outcome_type":"secondary","measure":"Positive Predictive Value (PPV) of Local Lab Tests Compared to Central Lab Test to Detect Rearranged during Transfection (RET) Gene Fusion","time_frame":"Baseline","description":"PPV of local lab tests compared to central lab test to detect RET gene fusion"},{"outcome_type":"secondary","measure":"Mean Change from Baseline over Time in NSCLC Symptoms","time_frame":"Baseline to treatment discontinuation (estimated as up to 3 years)","description":"NSCLC symptoms will be measured using the 7-item NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ). The NSCLC-SAQ measures the severity/frequency of the following core symptoms: Cough, pain, dyspnea, fatigue, and appetite. Raw scores range from 0 to 4 and the total score ranges from 0-20. Higher scores represent worse symptoms."},{"outcome_type":"secondary","measure":"Mean Change from Baseline over Time in Physical Function","time_frame":"Baseline to treatment discontinuation (estimated as up to 3 years)","description":"Physical function will be measured by the 5 physical function items in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) (also known as the EORTC IL 19 questionnaire). Raw scores range from 0-20. Higher scores indicate worst function."}]}
{"nct_id":"NCT05048797","start_date":"2021-10-29","phase":"Phase 3","enrollment":264,"brief_title":"A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations","official_title":"An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04)","primary_completion_date":"2025-01-17","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-03-01","last_update":"2021-09-17","description":"DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations","other_id":"D967SC00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"This study consists of two open-label treatment arms:\r\nArm 1: Trastuzumab Deruxtecan Arm 2: Standard of Care treatment (platinum, pemetrexed and pembrolizumab)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":123,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participants at least 18 years of age\r\n\r\n          -  Locally advanced not amenable to curative therapy, or metastatic disease\r\n\r\n          -  Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by\r\n             tissue NGS or ctDNA\r\n\r\n          -  Treatment-nave for palliative intent systemic therapy for locally advanced or\r\n             metastatic disease\r\n\r\n          -  Left ventricular ejection fraction (LVEF)  50%\r\n\r\n          -  Measurable disease assessed by Investigator based on RECIST 1.1\r\n\r\n          -  Protocol-defined adequate organ function including cardiac, renal, hepatic function\r\n\r\n          -  ECOG 0-1\r\n\r\n          -  Having tumour tissue available for central testing\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Tumors with targetable alterations to EGFR (or other targetable mutations including\r\n             but not limited to ALK, if routinely tested as a targetable alteration with approved\r\n             available therapy)\r\n\r\n          -  Any clinically active brain metastases; previously treated brain metastases allowed\r\n\r\n          -  Active autoimmune or inflammatory disorders\r\n\r\n          -  Medical history of myocardial infarction within 6 months prior to randomization\r\n\r\n          -  History of non-infectious pneumonitis/ILD, current or suspected ILD\r\n\r\n          -  Lung-specific intercurrent clinical significant severe illness\r\n\r\n          -  Contraindication to platinum-based doublet chemotherapy or pembrolizumab\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Locally Advanced or Metastatic Non-Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab Deruxtecan","description":"Trastuzumab Deruxtecan administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Pembrolizumab administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Pemetrexed administered by intravenous infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)","time_frame":"Until progression or death, assessed up to approximately 12 months","description":"Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Until death, assessed up to approximately 28 months.","description":"Defined as time from randomization until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) by investigator assessment","time_frame":"Until progression, assessed up to approximately 12 months","description":"Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Until progression, assessed up to approximately 12 months","description":"Defined as the proportion of participants who have a complete response (CR) or partial response (PR) as assessed by Blinded Independent Central Review (BICR) and investigator according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Until progression, assessed up to approximately 12 months","description":"Defined as the time from the date of first documented response until date of documented progression as assessed by Blinded Independent Central Review (BICR) and investigator assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Time to second progression or death (PFS2)","time_frame":"Assessed up to approximately 20 months","description":"Defined as the time from randomization until second progression on next-line of treatment as assessed by investigator at the local site using assessments conducted per local standard clinical practice, or death due to any cause."},{"outcome_type":"secondary","measure":"Landmark analysis of PFS (PFS12)","time_frame":"Assessed up to approximately 12 months","description":"Defined as proportion of participants alive and progression-free at 12 months, as assessed by Blinded Independent Central Review (BICR) and investigator."},{"outcome_type":"secondary","measure":"Landmark analysis of OS (OS24)","time_frame":"Assessed up to approximately 24 months","description":"Defined as proportion of participants alive at 24 months"},{"outcome_type":"secondary","measure":"Central Nervous System (CNS) - Progression Free Survival (PFS)","time_frame":"Until CNS progression or death, assessed up to approximately 12 months","description":"Defined as time from randomization until Central Nervous System (CNS) progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause in the absence of CNS progression."},{"outcome_type":"secondary","measure":"Safety and tolerability of T-DXd versus Standard of Care treatment","time_frame":"Until progression or death, assessed up to approximately 28 months","description":"Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, ECG, and ECHO/MUGA scan results."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum","time_frame":"Up to cycle 4, approximately 12 weeks","description":"Serum concentration of T-DXd, total anti-HER2 antibody and DXd."},{"outcome_type":"secondary","measure":"Immunogenicity of T-DXd","time_frame":"Until progression, assessed up to approximately 13 months","description":"Presence of anti-drug antibodies (ADAs) for T-DXd."},{"outcome_type":"secondary","measure":"Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer","time_frame":"Until progression, assessed up to approximately 13 months","description":"Time to sustained deterioration in pulmonary symptoms (cough, dyspnea, chest pain) while on treatment using the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ)."},{"outcome_type":"secondary","measure":"Patient-reported tolerability of T-DXd described using symptomatic AEs","time_frame":"Until progression, assessed up to approximately 13 months","description":"Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by the Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library."},{"outcome_type":"secondary","measure":"Patient-reported tolerability of T-DXd described using overall side-effect bother","time_frame":"Until progression, assessed up to approximately 13 months","description":"Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the Patient's Global Impression of Treatment Tolerability (PGI-TT) while on treatment."},{"outcome_type":"secondary","measure":"Patient-reported tolerability of T-DXd described using physical function","time_frame":"Until progression, assessed up to approximately 13 months","description":"Physical Function: The proportion of participants with maintained or improved physical function while on treatment, based on the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC-QLQ-C30) physical functioning scale."}]}
{"nct_id":"NCT04308785","start_date":"2021-10-29","phase":"Phase 2","enrollment":150,"brief_title":"A Study of Atezolizumab With or Without Tiragolumab Consolidation in Limited Stage Small Cell Lung Cancer","official_title":"A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 2 Study to Investigate the Efficacy and Safety of Atezolizumab With or Without Tiragolumab as Consolidation Therapy in Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed After Chemoradiotherapy","primary_completion_date":"2024-06-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-02-15","last_update":"2021-09-14","description":"This is a multicenter, double-blind, placebo-controlled, randomized, phase II study to investigate the efficacy and safety of Atezolizumab with or without Tiragolumab as consolidation therapy in participants with limited stage small cell lung cancer who have not progressed during/after chemoradiotherapy.","other_id":"ML41257","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Signed Informed Consent Form\r\n\r\n          -  ECOG performance status of 0 or 1\r\n\r\n          -  Histologically confirmed limited-stage SCLC.\r\n\r\n          -  Patients who have not progressed during/after chemoradiotherapy.\r\n\r\n          -  Concurrent or sequential chemoradiotherapy per local clinical practice must have been\r\n             completed within 6 weeks prior to the first study treatment. If concurrent CRT is\r\n             used, at least two cycles of chemotherapy should have been conducted during\r\n             radiotherapy. If sequential radiotherapy is used, induction chemotherapy should be\r\n             given 2 cycles of chemotherapy before thoracic radiotherapy.\r\n\r\n          -  Adequate hematologic and end organ function.\r\n\r\n          -  For women of childbearing potential: agreement to remain abstinent (refrain from\r\n             heterosexual intercourse) or use contraceptive methods that result in a failure rate\r\n             of < 1% per year during the treatment period and for at least 5 months after the final\r\n             dose of atezolizumab or placebo, and 90 days after the final dose of tiragolumab or\r\n             placebo, and 6 months for chemotherapy after the last dose of chemotherapy treatment,\r\n             whichever is later.\r\n\r\n          -  For men: agreement to remain abstinent or use contraceptive measures and agreement to\r\n             refrain from donating sperm.\r\n\r\n          -  Patients must have recovered from all acute toxicities from previous therapy,\r\n             excluding alopecia and toxicities related to prior therapy.\r\n\r\n          -  Patients must submit a pre-treatment tumor tissue sample.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Histology mixtured or Extensive-stage SCLC (per the Veterans Administration Lung Study\r\n             Group (VALG) staging system).\r\n\r\n          -  Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage\r\n             procedures\r\n\r\n          -  Evidence of significant uncontrolled concomitant disease that could affect compliance\r\n             with the protocol, including significant liver disease\r\n\r\n          -  Malignancies other than SCLC within 5 years prior to study treatment initiation, with\r\n             the exception of those with a negligible risk of metastasis or death treated with\r\n             expected curative outcome\r\n\r\n          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment\r\n             or within 5 months after the final dose of atezolizumab and 90 days after the final\r\n             dose of tiragolumab, and 6 months for chemotherapy after the final dose of the\r\n             chemotherapy treatment.\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  Uncontrolled or symptomatic hypercalcemia\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced\r\n             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening\r\n             chest CT scan.\r\n\r\n          -  Positive test result for HIV\r\n\r\n          -  Patients with active hepatitis B or hepatitis C virus\r\n\r\n          -  Active tuberculosis\r\n\r\n          -  Severe infections within 4 weeks prior to study treatment initiation, including but\r\n             not limited to hospitalization for complications of infection, bacteremia, or severe\r\n             pneumonia\r\n\r\n          -  Significant cardiovascular disease\r\n\r\n          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies,\r\n             anti-CTLA4, anti-tigit, anti-PD-1, and anti-PD-L1 therapeutic antibodies\r\n\r\n          -  Unresolved toxic effects of grade 2 or higher (CTCAE 5.0), including grade  2\r\n             pneumonitis from previous therapy\r\n\r\n          -  Active EBV infection or known or suspected chronic active EBV infection at screening.\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Carcinoma, Small Cell Lung","interventions":[{"intervention_type":"Other","name":"Other: Placebo","description":"Placebo matching to tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each cycle."},{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab will be administered at a dose of 1200 mg intravenously on the first day of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Tiragolumab","description":"Tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each 21-day cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population","time_frame":"Randomization up to approximately 48 months","description":"PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Overall Survival (OS) in the ITT Population","time_frame":"Randomization up to approximately 48 months","description":"OS is defined as the time from randomization to death from any cause or last follow-up."},{"outcome_type":"secondary","measure":"PFS Rate at 1 Year and 2 Years in the ITT Ppulation","time_frame":"Baseline to 1 Year and 2 Years","description":"PFS rate at 1 year and 2 years, defined as the proportion of patients remaining stable disease or ongoing response per RECIST v1.1 at 1 year and 2 years from the time of randomization."},{"outcome_type":"secondary","measure":"OS Rate at 1 Year, 2 Years and 3 Years in the ITT Population","time_frame":"Baseline to 1 Year, 2 Years and 3 Years","description":"OS rate at 1 year, 2 years and 3 years is defined as the proportion of patients remaining alive 1 year, 2 years and 3 years from the time of randomization."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) in the ITT Population","time_frame":"Randomization up to approximately 48 months","description":"ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1 in patients who have measurable disease at baseline."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) in the ITT Population","time_frame":"Time from first documentation of complete response (CR) or partial response (PR) up to approximately 48 months","description":"DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator according to the RECIST v1.1 or death from any cause, whichever occurs first, in the patients who have experienced a CR or PR (unconfirmed) during the study."},{"outcome_type":"secondary","measure":"Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Response to Chemoradiotherapy (CRT) [Stable Disease (SD) vs. Complete Response (CR)/Partial Response (PR)]","time_frame":"Randomization up to approximately 33 months","description":"PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Overall Survival (OS) in the ITT Population by Response to CRT (SD vs. CR/PR)","time_frame":"Randomization up to approximately 48 months","description":"OS is defined as the time from randomization to death from any cause or last follow-up."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) in the ITT Population by Response to CRT (SD vs. CR/PR)","time_frame":"Randomization up to approximately 48 months","description":"ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Radiotherapy Timing (Concurrent vs. Sequential)","time_frame":"Randomization up to approximately 48 months","description":"PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Overall Survival (OS) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)","time_frame":"Randomization up to approximately 48 months","description":"OS is defined as the time from randomization to death from any cause or last follow-up."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)","time_frame":"Randomization up to approximately 48 months","description":"ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Percentage of Participants With All Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population","time_frame":"Baseline up to approximately 48 months"},{"outcome_type":"secondary","measure":"Percentage of Participants With Serious and Non-Serious Immune Mediated Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population","time_frame":"Baseline up to approximately 48 months"},{"outcome_type":"secondary","measure":"Percentage of Participants With All Adverse Events Related to Treatment in the ITT Population","time_frame":"Baseline up to approximately 48 months"},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Patient-Rported Lung Cancer Symptoms","time_frame":"Randomization up to approximately 48 months","description":"TTD is defined as the time from randomization to a patient's first ≥10-point score change from baseline in a scale maintained for at least two consecutive PRO assessments, or followed by death within 3 weeks of the first ≥10-point score change."},{"outcome_type":"secondary","measure":"EORTC QLQ-C30 Score","time_frame":"Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months","description":"EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 Questionnaire, is a validated, reliable self-report measure. It consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales."},{"outcome_type":"secondary","measure":"EORTC QLQ-LC13 Score","time_frame":"Day 1 of first 3 cycles (cycle length=21 days), then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months","description":"The EORTC, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, QLQ-LC13 is a modular supplement to the EORTC quality-of-life questionnaire for use in lung cancer. This module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis."},{"outcome_type":"secondary","measure":"EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Based and Visual Analogue Scale (VAS) Scores","time_frame":"Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months","description":"The EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single composite score of the patient's health status."}]}
{"nct_id":"NCT05038735","start_date":"2021-10-27","phase":"Phase 3","enrollment":234,"brief_title":"Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.","official_title":"EPIK-B5: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With HR-positive, HER2-negative Advanced Breast Cancer With a PIK3CA Mutation, Who Progressed on or After Aromatase Inhibitor and a CDK4/6 Inhibitor","primary_completion_date":"2026-10-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-11-27","last_update":"2021-09-09","description":"The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor.","other_id":"CBYL719C2303","allocation":"Randomized","intervention_model":"Crossover Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participant is an adult  18 years old at the time of informed consent and has signed\r\n             informed consent before any trial related activities and according to local\r\n             guidelines.\r\n\r\n          -  If female, then the participant must be in postmenopausal status. Postmenopausal\r\n             status is defined either by: prior bilateral oophorectomy, age 60 or age <60 and\r\n             amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen,\r\n             toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and\r\n             estradiol in the postmenopausal range per local normal range.\r\n\r\n          -  Participant has a histologically and/or cytologically confirmed diagnosis of ER+\r\n             and/or PgR+ breast cancer by local laboratory.\r\n\r\n          -  Participant has HER2-negative breast cancer defined as a negative in situ\r\n             hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ\r\n             hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ\r\n             hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is\r\n             required by local laboratory testing.\r\n\r\n          -  Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed\r\n             by BIRC (a lesion at a previously irradiated site may only be counted as a target\r\n             lesion if there is clear sign of progression since the irradiation).\r\n\r\n          -  Participant has recurrence or progression of disease during or after combined AI (i.e.\r\n             letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and\r\n             CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including\r\n             adjuvant setting).\r\n\r\n          -  Participant has received 1 line of prior treatment with chemotherapy (except for\r\n             neoadjuvant/ adjuvant chemotherapy).\r\n\r\n          -  Participant must show the presence of a PIK3CA mutation(s) determined by tissue either\r\n             by a local laboratory using only CE-marked IVD assays such as QIAGEN Therascreen\r\n             PIK3CA RGQ PCR test or by a Novartis designated laboratory.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participant with symptomatic visceral disease that makes the participant ineligible\r\n             for endocrine therapy (ET) per the investigator's best judgment.\r\n\r\n          -  Participant who relapsed with documented evidence of progression more than 12 months\r\n             from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic\r\n             disease\r\n\r\n          -  Participant has received prior treatment with fulvestrant, any\r\n             Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein\r\n             Kinase B (AKT) inhibitor\r\n\r\n        Other Inclusion and Exclusion Criteria do apply\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Alpelisib","description":"Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle."},{"intervention_type":"Drug","name":"Drug: Fulvestrant","description":"Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days)."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria","time_frame":"From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.","description":"To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to treatment with placebo plus fulvestrant. PFS is the defined as the time from randomization to date of randomization to the date of the first documented progression as per BIRC criteria using RECIST v1.1 or death due to any cause, whichever comes first."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From the date of randomization to the date of death up to a maximum duration of 60 months","description":"To determine whether treatment with alpelisib plus fulvestrant prolongs overall survival (OS) compared to treatment with placebo plus fulvestrant. OS is defined as the time from randomization to the date of death due to any cause"},{"outcome_type":"secondary","measure":"Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria","time_frame":"From the date of randomization up to a maximum duration of 60 months","description":"To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. Overall response rate (ORR) with confirmed response is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per BIRC and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria","time_frame":"From the date of randomization up to a maximum duration of 60 months","description":"To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. CBR with confirmed response is defined as the proportion of participants with a best overall response of confirmed CR or PR, or SD lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per BIRC review according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria","time_frame":"From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months","description":"To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. Duration of response (DOR) with confirmed response only applies to participants whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per BIRC review. The start date is the date of first documented response of CR or PR and the end date is defined as the date of the first documented progression or death due to underlying cancer."},{"outcome_type":"secondary","measure":"Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria","time_frame":"From the date of randomization to the first documented response up to a maximum duration of 60 months","description":"To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria. Time to response (TTR) is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed. CR and PR are based on tumor response data as per BIRC review and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status","time_frame":"From the date of randomization up to a maximum duration of 60 months","description":"To evaluate the association between PIK3CA mutation status with PFS upon treatment with alpelisib. PFS is the defined as the time from randomization to date of randomization to the date of the first documented progression as per BIRC criteria using RECIST v1.1 or death due to any cause, whichever comes first. Results will be presented by PIK3CA mutation status measured in circulating tumor deoxyribonucleic acid (ctDNA) collected at baseline."},{"outcome_type":"secondary","measure":"Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline","time_frame":"From the date of randomization up to maximum duration of 60 months","description":"To evaluate treatment with alpelisib plus fulvestrant compared to placebo plus fulvestrant, with respect to time to deterioration of ECOG performance status. Time to definitive deterioration in ECOG PS is defined as the time from the date of randomization to the date when ECOG PS has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or above."},{"outcome_type":"secondary","measure":"Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)","time_frame":"From the date of randomization up to maximum duration of 60 months","description":"To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant. Time from date of randomization to date of event, defined as at least a 10% worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause, in the global health status/QOL and symptom scale scores of EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items and a global health status/QoL scale. The scales and single-item measures range in score from 0 - 100. A high scale score represents a higher response level."},{"outcome_type":"secondary","measure":"Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30","time_frame":"From the date of randomization up to maximum duration of 60 months","description":"To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant. Change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment. EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items and is composed of both multi-item scales and single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items and a global health status/QoL scale. The scales and single-item measures range in score from 0 - 100. A high scale score represents a higher response level."},{"outcome_type":"secondary","measure":"Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)","time_frame":"From the date of randomization up to maximum duration of 60 months","description":"To explore the long-term benefit intermediate to PFS and OS. PFS2 is defined as time from date of randomization to the first documented progression on nextline therapy or death from any cause, whichever occurs first. Disease progression will be determined based on investigator assessment of progression on next-line therapy."}]}
{"nct_id":"NCT04952753","start_date":"2021-10-15","phase":"Phase 2","enrollment":190,"brief_title":"Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC","official_title":"An Open-label, Multi-center, ph II Platform Study Evaluating the Efficacy and Safety of NIS793 and Other New Investigational Drug Combinations With SOC Anti-cancer Therapy for the 2L Treatment of Metastatic Colorectal Cancer (mCRC)","primary_completion_date":"2023-11-22","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-12-25","last_update":"2021-07-07","description":"The purpose of this study is to evaluate the preliminary efficacy and safety of NIS793 and other novel investigational combinations with standard of care (SOC) anti-cancer therapy vs SOC anti-cancer therapy for the second line treatment of mCRC. This study aims to explore whether different mechanisms of action may reverse resistance and improve responsiveness to the currently considered SOC anti-cancer therapy in the second line metastatic colorectal cancer (mCRC) setting.","other_id":"CNIS793E12201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Participants age 18 or older with histologically or cytologically confirmed (by local\r\n             laboratory and local clinical guidelines) metastatic colorectal adenocarcinoma that is\r\n             not amenable to potentially curative surgery in the opinion of the investigator and\r\n             progressed on or within 6 months after the last dose of one prior line of systemic\r\n             anti-cancer therapy administered for metastatic disease.\r\n\r\n          -  Presence of at least one measurable lesion assessed by CT and/or MRI according to\r\n             RECIST 1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.\r\n\r\n          -  Adequate organ function (assessed by central laboratory for eligibility).\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Previously administered systemic TGF- targeted therapies.\r\n\r\n          -  Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or\r\n             BRAFV600 mutation positive colorectal cancer.\r\n\r\n          -  Known complete or partial dipyrimidine dehydrogenase (DPD) enzyme deficiency (testing\r\n             for DPD enzyme deficiency is not mandatory unless required by local regulations and\r\n             can be conducted at a local laboratory).\r\n\r\n          -  For participants treated with irinotecan: Known history or clinical evidence of\r\n             reduced UGT1A1 activity (testing for UGT1A1 status is not mandatory unless required by\r\n             local regulations and can be conducted at a local laboratory).\r\n\r\n          -  Participants who have not recovered from a major surgery performed prior to start of\r\n             study treatment or have had a major surgery within 4 weeks prior to start of study\r\n             treatment.\r\n\r\n          -  Impaired cardiac function or clinically significant cardio-vascular disease.\r\n\r\n          -  Participants with conditions that are considered to have a high risk of clinically\r\n             significant gastrointestinal tract bleeding or any other condition associated with or\r\n             history of significant bleeding.\r\n\r\n          -  Stroke or transient ischemic attack, or other ischemic event, or thromboembolic event\r\n             (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before start of\r\n             study treatment.\r\n\r\n          -  Pregnant or breast-feeding women.\r\n\r\n          -  Women of childbearing potential, unless willing to use highly effective contraception\r\n             methods during treatment and after stopping study treatments as required.\r\n\r\n        Other inclusion/exclusion criteria may apply\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: NIS793","description":"Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part."},{"intervention_type":"Drug","name":"Drug: Bevacizumab","description":"Bevacizumab will be administered IV"},{"intervention_type":"Drug","name":"Drug: Modified FOLFOX6","description":"5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and oxaliplatin [administered IV]"},{"intervention_type":"Drug","name":"Drug: FOLFIRI","description":"5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and irinotecan [administered IV]"}],"outcomes":[{"outcome_type":"primary","measure":"Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.","time_frame":"Up to 4 weeks","description":"Percentage of participants with DLTs during the first cycle of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 in combination with Bevacizumab and modified FOLFOX6/ FOLFIRI"},{"outcome_type":"primary","measure":"Expansion: Progression-free survival (PFS) by investigator assessment per RECIST 1.1","time_frame":"From randomization up to disease progression or death, assessed up to approximately 12 months","description":"PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause."},{"outcome_type":"secondary","measure":"Safety run-in: Percentage of participants with Adverse Events (AEs)","time_frame":"Up to approximately 12 months","description":"Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments"},{"outcome_type":"secondary","measure":"Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug","time_frame":"Upto approximately 12 months","description":"Tolerability measured by the percentage of subjects who have dose adjustements (interruptions or reductions) of investigational drug (e.g. NIS793)"},{"outcome_type":"secondary","measure":"Safety run-in: Dose intensity of investigational drug","time_frame":"Up to approximately 12 months","description":"Tolerability measured by the dose intensity of investigational drug (e.g. NIS793). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure"},{"outcome_type":"secondary","measure":"Safety run-in: PFS by investigator assessment per RECIST 1.1","time_frame":"From enrollment up to disease progression or death, assessed up to approximately 12 months","description":"PFS defined as the time from the date of enrollment to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause."},{"outcome_type":"secondary","measure":"Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 12 months","description":"ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 12 months","description":"DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1","time_frame":"From first documented response up to disease progression or death, assessed up to approximately 12 months","description":"DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause"},{"outcome_type":"secondary","measure":"Safety run-in part: Overall Survival (OS)","time_frame":"From enrollment up to death, assessed up to approximately 12 months","description":"OS is defined as the time from the date of enrollment to date of death due to any cause."},{"outcome_type":"secondary","measure":"Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1","time_frame":"From enrollment up to first documented response, assessed up to approximately 12 months","description":"TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR."},{"outcome_type":"secondary","measure":"Expansion: Percentage of participants with Adverse Events (AEs)","time_frame":"Up to approximately 12 months","description":"Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments"},{"outcome_type":"secondary","measure":"Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug","time_frame":"Up to approximately 12 months","description":"Tolerability measured by the percentage of subjects who have dose adjustments (interruptions) of investigational drug (e.g. NIS793)"},{"outcome_type":"secondary","measure":"Expansion: Dose intensity of investigational drug","time_frame":"Up to approximately 12 months","description":"Tolerability measured by the dose intensity of investigational drug (e.g. NIS793). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure"},{"outcome_type":"secondary","measure":"Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 12 months","description":"ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 12 months","description":"DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Expansion part: Overall Survival (OS)","time_frame":"From randomization up to death, assessed up to approximately 12 months","description":"OS is defined as the time from the date of enrollment to date of death due to any cause."},{"outcome_type":"secondary","measure":"Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1","time_frame":"From enrollment up to first documented response, assessed up to approximately 12 months","description":"TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR."},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax) of NIS793","time_frame":"From the date of first study drug intake up to approximately 12 months","description":"Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793"},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax) of bevacizumab","time_frame":"From the date of first study drug intake up to approximately 12 months","description":"Blood samples will be collected at indicated time-points for analysis of Cmax of bevacizumab"},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax) of irinotecan and its metabolite (SN38)","time_frame":"From the date of first study drug intake up to approximately 12 months","description":"Blood samples will be collected at indicated time-points for analysis of Cmax of irinotecan and SN-38"},{"outcome_type":"secondary","measure":"Trough Concentration (Ctrough) of NIS793","time_frame":"From the date of first study drug intake up to approximately 12 months","description":"Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793"},{"outcome_type":"secondary","measure":"Trough Concentration (Ctrough) of bevacizumab","time_frame":"From the date of first study intake up to approximately 12 months.","description":"Blood samples will be collected at indicated time-points for analysis of Ctrough of bevacizumab"},{"outcome_type":"secondary","measure":"Trough Concentration (Ctrough) of irinotecan and its metabolite (SN38)","time_frame":"From the date of first study drug intake up to approximately 12 months.","description":"Blood samples will be collected at indicated time-points for analysis of Ctrough of irinotecan and SN-38"},{"outcome_type":"secondary","measure":"Antidrug antibodies (ADA) at baseline","time_frame":"Baseline","description":"Prevalence of ADA (anti-NIS793, anti-bevacizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline"},{"outcome_type":"secondary","measure":"ADA incidence on treatment","time_frame":"From the date of first study drug intake up to approximately 12 months","description":"Incidence of ADA (anti-NIS793, anti-bevacizumab) on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)"}]}
{"nct_id":"NCT04935359","start_date":"2021-10-13","phase":"Phase 3","enrollment":490,"brief_title":"Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)","official_title":"A Randomized, Double-blind, Phase III Study, Comparing NIS793 in Combination With Gemcitabine and Nab-paclitaxel Versus (vs.) Placebo Combined With Gemcitabine and Nab-paclitaxel for First Line Treatment of Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)","primary_completion_date":"2026-01-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-01-01","last_update":"2021-06-23","description":"The purpose of this study is to evaluate the efficacy and safety of NIS793 in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel and placebo in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). This study aims to explore whether blockade of Transforming Growth Factor  (TGF) in combination with gemcitabine/nab-paclitaxel can reduce fibrosis in PDAC, restore chemo-sensitivity and ultimately lead to improvements in overall survival (OS) and other clinically relevant outcomes.","other_id":"CNIS793B12301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Applicable for both Safety run-in and Randomized part\r\n\r\n               -  Participants aged 18 years with histologically or cytologically confirmed (based\r\n                  on local assessment and per local guidelines) mPDAC eligible for treatment in the\r\n                  first line setting and not amenable for potentially curative surgery\r\n\r\n               -  Presence of at least one measurable lesion assessed by Computerized Tomography\r\n                  (CT) and/or Magnetic Resonance Imaging (MRI) according to RECIST 1.1\r\n\r\n               -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1\r\n\r\n               -  Adequate organ function (assessed by central laboratory for eligibility)\r\n\r\n               -  Participants must have recovered from treatment-related toxicities of prior\r\n                  anticancer therapies to grade  1 (CTCAE v 5.0) at time of screening, except\r\n                  alopecia.\r\n\r\n        Main Exclusion Criteria:\r\n\r\n          -  Applicable for both Safety run-in and Randomized part\r\n\r\n               -  Previous systemic anti-cancer treatment for metastatic PDAC\r\n\r\n               -  Pancreatic neuroendocrine, acinar, or islet tumors\r\n\r\n               -  Participants with known status of microsatellite instability-high (MSI-H) or\r\n                  mismatch repair-deficient pancreatic cancer (if status is not already available,\r\n                  testing is not required at screening).\r\n\r\n               -  Participant has not recovered from a major surgery performed prior to start of\r\n                  study treatment or has had a major surgery within 4 weeks prior to start of study\r\n                  treatment.\r\n\r\n               -  Radiation therapy or brain radiotherapy  4 weeks prior to start of study\r\n                  treatment (palliative radiotherapy to bone lesions allowed  2 weeks prior to\r\n                  start of study treatment).\r\n\r\n               -  Impaired cardiac function or clinically significant cardio-vascular disease\r\n\r\n               -  Use of hematopoietic growth factors or transfusion support  2 weeks prior to\r\n                  start of study treatment.\r\n\r\n               -  Participant has conditions that are considered to have a high risk of clinically\r\n                  significant gastrointestinal tract bleeding or any other condition associated\r\n                  with or history of significant bleeding.\r\n\r\n               -  Serious non-healing wounds.\r\n\r\n               -  Pregnant or breast-feeding women\r\n\r\n               -  Women of childbearing potential, unless willing to use highly effective\r\n                  contraception methods during treatment and after stopping study treatments as\r\n                  indicated\r\n\r\n               -  Pre-existing peripheral neuropathy > grade 1 (CTCAE v5.0)\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Metastatic Pancreatic Ductal Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: NIS793","description":"Concentrate for solution infusion (Liquid in Vial)"},{"intervention_type":"Drug","name":"Drug: Nab-paclitaxel","description":"Powder for solution for infusion"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Powder for solution for infusion"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Dextrose 5% in water (D5W) solution ofr infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Safety run-in part: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.","time_frame":"Up to 4 weeks","description":"Percentage of participants with DLTs during the first cycle of treatment in the safety run-in part. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 in combination with gemcitabine and nab-paclitaxel"},{"outcome_type":"primary","measure":"Randomized part: Overall survival (OS)","time_frame":"From randomization up to death, assessed up to approximately 19 months","description":"OS is defined as the time from date of randomization to date of death due to any cause."},{"outcome_type":"secondary","measure":"Percentage of participants with Adverse Events (AEs)","time_frame":"Up to approximately 19 months","description":"Percentage of participants with AEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments"},{"outcome_type":"secondary","measure":"Percentage of participants with dose interruptions and dose reductions of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"Up to approximately 19 months","description":"Tolerability measured by the percentage of participants who have dose adjustments (interruptions or reductions) of NIS793"},{"outcome_type":"secondary","measure":"Dose intensity of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"Up to approximately 19 months","description":"Tolerability measured by the dose intensity of NIS793. Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) by investigator assessment per RECIST 1.1","time_frame":"From enrollment (run-in part) or randomization (randomized part) up to disease progression or death, assessed up to approximately 19 months","description":"PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause."},{"outcome_type":"secondary","measure":"Overall response rate (ORR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 19 months","description":"ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) by investigator assessment per RECIST 1.1","time_frame":"Up to approximately 19 months","description":"DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Time to response (TTR) by investigator assessment per RECIST 1.1","time_frame":"From enrollment (run-in part) or randomization (randomized part) up to first documented response, assessed up to approximately 19 months","description":"TTR is defined as the duration of time between the date of enrollment (run-in part) or randomization (randomized part) and the date of first documented response of either CR or PR."},{"outcome_type":"secondary","measure":"Safety run-in part: Overall Survival (OS)","time_frame":"From enrollment up to death, assessed up to approximately 19 months","description":"OS is defined as the time from the date of enrollment to date of death due to any cause."},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax) of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of Cmax of NIS793"},{"outcome_type":"secondary","measure":"Trough Concentration (Ctrough) of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of Ctrough of NIS793"},{"outcome_type":"secondary","measure":"Area under the curve from time zero to the last measurable concentration sampling time (AUClast) of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of AUClast of NIS793"},{"outcome_type":"secondary","measure":"Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of AUCtau of NIS793"},{"outcome_type":"secondary","measure":"Time to reach maximum concentration (Tmax) of NIS793 in combination with gemcitabine and nab-paclitaxel","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of Tmax of NIS793"},{"outcome_type":"secondary","measure":"Randomized part: NIS793 serum concentration","time_frame":"From date of first study drug intake up to approximately 19 months","description":"Blood samples will be collected for analysis of NIS793 serum concentration"},{"outcome_type":"secondary","measure":"Randomized part: Change from baseline in the patient reported outcomes measurement information system (PROMIS)-29 profile scores at week 12","time_frame":"Week 12","description":"PROMIS is a commonly used self-reported measurement system of health-related quality of life and physical function. The PROMIS-29 includes 29 items that assess seven domains: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference and pain intensity. Questions are ranked on a 5-point response scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level. Scores will be reported for each domain, as well as for pain rating."},{"outcome_type":"secondary","measure":"Randomized part: Change from baseline in the European Quality of life questionnaire (EQ-5D-5L) scores (health index and EQ-VAS) at week 12","time_frame":"Week 12","description":"The EQ-5D-5L is a 2-part questionnaire: the descriptive system and the EQ visual analogue scale (EQ-VAS). The first part assesses participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The health state index score is calculated based on the responses to the 5 dimensions, providing a single value on a scale from -0.285 to 0.950, with higher scores indicating better health utility. The EQ-VAS records the respondent's self-rated health on a visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine."},{"outcome_type":"secondary","measure":"Randomized part: Time-to-deterioration in domain scores in the PROMIS-29 profile","time_frame":"From randomization up to deterioration or death, assessed up to approximately 19 months","description":"A clinically meaningful deterioration or worsening in the domain will be defined according to change from baseline scores according to minimally important differences (MID) estimates for each domain. Time-to-deterioration is defined as the time from baseline to the date of deterioration event or death due to any cause. The event of deterioration is defined as the change from baseline (worsening) of the corresponding PROMIS-29 score ≥MID, with no later change below the thereshold"},{"outcome_type":"secondary","measure":"Randomized part: Time-to-deterioration in EQ-5D-5L scores (health index and EQ-VAS)","time_frame":"From randomization up to deterioration, assessed up to approximately 19 months","description":"The EQ-5D-5L is a 2-part questionnaire: the descriptive system and the EQ-VAS. The first part assesses participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 levels. The health state index score is calculated based on the responses to the 5 dimensions, providing a single value on a scale from -0.285 to 0.950, with higher scores indicating better health. The EQ-VAS records the respondent's self-rated health on a visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.\r\nTime-to-deterioration is defined as the time from baseline to the date of deterioration event or death due to any cause. The event of deterioration is defined as the change from baseline (worsening) in the corresponding index score ≥ 7 (EuroQol visual analogue scale) or ≥8 (health index)."},{"outcome_type":"secondary","measure":"Randomized part: Anti-drug antibodies (ADA) against NIS793 prevalence at baseline","time_frame":"Baseline","description":"ADA (anti-NIS793) prevalence at baseline is defined as the proportion of participants who have an ADA positive result at baseline"},{"outcome_type":"secondary","measure":"Randomized part: ADA (anti-NIS793) incidence on treatment","time_frame":"From date of first study drug intake up to approximately 19 months","description":"ADA (anti-NIS793) incidence on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)"}]}
{"nct_id":"NCT05043090","start_date":"2021-10-08","phase":"Phase 3","enrollment":200,"brief_title":"Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC","official_title":"A Phase III, Open Label, Randomised, 3-Arm, Multi-Centre Study of Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (SAMETA)","primary_completion_date":"2024-03-08","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-05-20","last_update":"2021-09-13","description":"A clinical trial to compare the effectiveness of savolitinib plus durvalumab versus sunitinib in MET-driven (hepatocyte growth factor receptor), unresectable and locally advanced or metastatic PRCC (Papillary Renal Cell Carcinoma)","other_id":"D5086C00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed unresectable and locally advanced or metastatic PRCC\r\n\r\n          -  PRCC must be centrally confirmed as MET-driven using a sponsor-designated central\r\n             laboratory validated NGS assay\r\n\r\n          -  No prior systemic anti-cancer treatment in the metastatic setting; no prior exposure\r\n             to MET inhibitors, Durvalumab or Sunitinib in any setting\r\n\r\n          -  Karnofsky Score >70\r\n\r\n          -  At least one lesion, not previously irradiated, that can be accurately measured at\r\n             baseline\r\n\r\n          -  Adequate organ and bone marrow function\r\n\r\n          -  Life expectancy 12weeks at Day 1\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of serious liver disease, with or without, normal LFTs, such as cirrhosis or\r\n             Wilson's disease\r\n\r\n          -  Spinal cord compression or brain metastases, unless asymptomatic and stable on\r\n             treatment for at least 14 days prior to study intervention\r\n\r\n          -  Active or prior cardiac disease (within past 6 months) or clinically significant ECG\r\n             abnormalities and/or factors/medications that may affect QT and/or QTc intervals\r\n\r\n          -  Active infection including HIV, TB, HBV and HCV\r\n\r\n          -  Active or prior documented autoimmune or inflammatory disorders\r\n\r\n          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of study\r\n             intervention\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Papillary Renal Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: savolitinib","description":"Tablets : 3  200 mg tablets once daily"},{"intervention_type":"Drug","name":"Drug: durvalumab","description":"Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks"},{"intervention_type":"Drug","name":"Drug: sunitinib","description":"Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off"}],"outcomes":[{"outcome_type":"secondary","measure":"Evaluation of the PK of savolitinib pre-dose","time_frame":"Approximately 28 months post first subject randomized","description":"Plasma concentration of savolitinib and its metabolites pre-dose (Ctrough / trough plasma concentration : measured concentration at the end of a dosing interval at steady state [taken directly before next administration]) in participants randomised to savolitinib plus durvalumab."},{"outcome_type":"primary","measure":"Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.\r\nThe analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression."},{"outcome_type":"secondary","measure":"Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months and approximately 42 months post first subject randomized","description":"Defined as time from randomisation until the date of death due to any cause. The comparison will include all randomised participants as randomised regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as the percentage of participants who have a CR or PR or who have Stable Disease (SD) per RECIST 1.1 as assessed by BICR for at least 23 or 47 weeks, respectively after randomisation."},{"outcome_type":"secondary","measure":"Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months and 42 months post first subject randomized","description":"Defined as time from randomisation to the earliest of the progression event (following the initial progression), subsequent to the first subsequent therapy or death."},{"outcome_type":"secondary","measure":"Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib","time_frame":"Approximately 28 months post first subject randomized","description":"Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by FKSI-19."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy","time_frame":"Approximately 28 months post first subject randomized","description":"Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.\r\nThe analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression."},{"outcome_type":"secondary","measure":"Evaluation of the PK of savolitinib post-dose","time_frame":"Approximately 28 months post first subject randomized","description":"Plasma concentration of savolitinib and its metabolites post-dose (C1h and C3h) in participants randomised to savolitinib plus durvalumab."},{"outcome_type":"secondary","measure":"Evaluation of the PK of durvalumab pre-dose","time_frame":"Approximately 28 months post first subject randomized","description":"Serum concentration of durvalumab pre-dose (Ctrough / trough plasma concentration : measured concentration at the end of a dosing interval at steady state [taken directly before next administration]) in participants randomised to savolitinib plus durvalumab or durvalumab monotherapy."},{"outcome_type":"secondary","measure":"Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration)","time_frame":"Approximately 28 months post first subject randomized","description":"Serum concentration of durvalumab at the end of infusion (Cmax) in participants randomised to savolitinib plus durvalumab or durvalumab monotherapy."}]}
{"nct_id":"NCT04940052","start_date":"2021-10-01","phase":"Phase 3","enrollment":150,"brief_title":"Study of Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer","official_title":"A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer (DTC)","primary_completion_date":"2024-02-19","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-10-30","last_update":"2021-06-25","description":"150 adults patients with locally advanced or metastatic BRAFV600E mutation-positive, differentiated thyroid carcinoma who are refractory to radioactive iodine and have progressed following prior VEGFR targeted therapy will enter in the trial. Patients will be randomized in a 2:1 ratio to either dabrafenib plus trametinib or placebo. Patients will be stratified by number of prior VEGFR targeted therapy (1versus2) and prior lenvatinib treatment (yes versus no)","other_id":"CDRB436J12301","allocation":"Randomized","intervention_model":"Crossover Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Signed informed consent must be obtained prior to performing any specific\r\n             pre-screening and screening procedure\r\n\r\n          -  Male or female >= 18 years of age at the time of informed consent\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of advanced/metastatic\r\n             differentiated thyroid cancer\r\n\r\n          -  Radio active iodine refractory disease\r\n\r\n          -  BRAFV600E mutation positive tumor sample as per Novartis designated central laboratory\r\n             result\r\n\r\n          -  Has progressed on at least 1 but not more than 2 prior VEGFR targeted therapy\r\n\r\n          -  Eastern Cooperative Oncology Group performance status >= 2\r\n\r\n          -  At least one measurable lesion as defined by RECIST 1.1\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Anaplastic or medullary carcinoma of the Tyroid\r\n\r\n          -  Previous treatment with BRAF inhibitor and/or MEK inhibitor\r\n\r\n          -  Concomitant RET Fusion Positive Thyroid cancer\r\n\r\n          -  Receipt of any type of small molecule kinase inhibitor within 2 weeks before\r\n             randomization\r\n\r\n          -  Receipt of any type of cancer antibody or systemic chemotherapy within 4 weeks before\r\n             randomization\r\n\r\n          -  Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation\r\n             therapy within 4 weeks before randomization\r\n\r\n          -  A history or current evidence/risk of retinal vein occlusion or central serous\r\n             retinopathy\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Differentiated Thyroid Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Dabrafenib","description":"Dabrafenib will be administered orally twice daily"},{"intervention_type":"Drug","name":"Drug: Trametinib","description":"Trametinib will be administered orally once daily"},{"intervention_type":"Drug","name":"Drug: Trametinib placebo","description":"Trametinib will be administered orally once daily"},{"intervention_type":"Drug","name":"Drug: Dabrafenib placebo","description":"Dabrafenib placebo will be administered orally twice daily"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival","time_frame":"From randomization to first documented progression or deaths, whichever comes first, assessed up to approximately 2 years","description":"Progression Free Survival is based on the blinded independent review committee assessment using RECIST 1.1"},{"outcome_type":"secondary","measure":"Overall Response Rate","time_frame":"From randomization up to approximately 2 years","description":"overall response rate is defined as the proportion of patients with best overall response of complete response or partial response assessed per blinded independent review committee using RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"From randomization to death assessed up to approximately 5 years","description":"Overall survival is defined as the time from the date of randomization to the date of death to any cause."},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"Duration of response from the start date of the first documented response of complete response or partial response and the date defined as the date of the first documented progression or death due to any cause up to 2 years","description":"Duration of response only applies to patients whose best overall response is complete response or partial response according to RECIST 1.1 and based on blinded independent review committee."},{"outcome_type":"secondary","measure":"Number of participants with trametinib associated serous retinopathy ocular events","time_frame":"screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years","description":"Standard ophthalmic examination will by done by an ophthalmologist and optical coherence tomography conducted at mandated visit. Analysis using optical coherence tomography data will be done to assess the incidence, type and severity of ocular events"}]}
{"nct_id":"NCT04736394","start_date":"2021-10-01","phase":"Phase 3","enrollment":800,"brief_title":"A Phase 3 Study to Evaluate the Safety and Efficacy of APL-1202 as a Single-agent Oral Treatment Versus Intravesical Instillation of Epirubicin Hydrochloride in nave Intermediate-risk NMIBC Patients","official_title":"A Multi-center, Randomized, Open-label, Parallel-controlled Phase 3 Clinical Trial to Evaluate the Clinical Safety and Efficacy of APL-1202 as a Single-agent Oral Treatment Versus Intravesical Instillation of Epirubicin Hydrochloride in nave Intermediate-risk Non-muscle Invasive Bladder Cancer (NMIBC) Patients","primary_completion_date":"2025-03-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-12-31","last_update":"2021-06-24","description":"A multi-center, randomized, open-label, parallel-controlled Phase  clinical trial to evaluate the clinical safety and efficacy of APL-1202 as a single-agent oral treatment versus intravesical instillation of Epirubicin hydrochloride in nave intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients","other_id":"YHCT-NIT-R2","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        All patients must meet all the following criteria:\r\n\r\n          -  Must be informed of the investigational nature of this study and must provide written\r\n             informed consent\r\n\r\n          -  Age 18 years, male or female\r\n\r\n          -  Non-muscle invasive transitional cell carcinoma of the bladder is histologically\r\n             confirmed by Independent Pathology Review Committee (IPRC). Diagnosis and\r\n             classification of intermediate-risk NMIBC is according to 2014 CUA Guideline of\r\n             Diagnosis and Treatment of Urological Diseases in China:\r\n\r\n        Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, no CIS.\r\n        (Note: the above conditions must be met at the same time as a low-risk NMIBC)\r\n        Intermediate-risk: All tumours not defined in the two adjacent categories (between the\r\n        category of low and high risk) High-risk: Any of the following:  T1 tumour; G3(high-grade\r\n        urothelial carcinoma) tumour;carcinoma in situ (CIS);  Multiple, recurrent and large (> 3\r\n        cm) TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)\r\n\r\n         No visible tumor after transurethral resection of bladder tumor (TURBT) on tumor lesion.\r\n        Some requirements about Re-TURBT are as follows: It is recommended to conduct the secondary\r\n        TURBT under following situations: incomplete first TURBT; no muscle tissue found in the\r\n        first TURBT specimen, except Ta G1 (low grade) tumor and CIS only.\r\n\r\n        The secondary TURBT is recommended 2-6 weeks, but better at 4 weeks, after the first TURBT.\r\n\r\n        For subjects undergoing secondary TURBT, they will be enrolled after the second TURBT\r\n\r\n          -  Subjects who never received intravesical instillation (including BCG or intravesical\r\n             chemotherapy) prior to enrollment, except single, immediate, post-operative\r\n             intravesical chemotherapy.\r\n\r\n          -  Willing to provide pathological tissue specimen for assessment\r\n\r\n          -  ECOG PS  1\r\n\r\n          -  Patients, who have not received blood transfusion or colony-stimulating factor\r\n             treatment within 14 days before the examination, must have normal organ and marrow\r\n             function within 42 days of study entry (according to normal range in clinical site).\r\n\r\n        Absolute neutrophil count >1.5109/L Platelets > 100 109/L Hemoglobin > 9.0 g/dL Alkaline\r\n        phosphatase < 2.5 ULN GFR (Cockcroft-Gault formula calculated)  50 mL/min Total bilirubin,\r\n        alanine aminotransferase or aspartate aminotransferase< 1.5 ULN INR <1.5, except for\r\n        subjects receiving anticoagulation therapy\r\n\r\n          -  Female should be either surgically sterilized or menopause or agree to use effective\r\n             contraceptive measures during treatment. Women of reproductive age must have a\r\n             negative result of pregnancy test during the screening period (pregnancy test will be\r\n             not required if one of the following situations exists: the subject has undergone\r\n             sterilization such as hysterectomy and/or bilateral oophorectomy, has no menstruation\r\n             for 12 months and been diagnosed as menopause based on factors such as age). However,\r\n             pregnancy tests are required for patients with bilateral fallopian tube ligation.\r\n\r\n          -  Male subjects should be either surgically sterilized or agreed to use effective\r\n             contraceptive measures. From signing the informed consent, subjects must take\r\n             continuous measures until 3 months after the end of the treatment of trial. The\r\n             definition of effective contraceptive measures will be based on the principal\r\n             investigator(PI) or appointed delegate.\r\n\r\n          -  Expected life expectancy is more than 48 months\r\n\r\n        Exclusion Criteria:\r\n\r\n        The presence of any of the following will exclude a patient from study enrollment:\r\n\r\n          -  Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, no\r\n             CIS. (PS: the above conditions must be met at the same time as a low-risk NMIBC)\r\n\r\n          -  High-risk: Any of the following:  T1 tumour; G3(high-grade urothelial carcinoma)\r\n             tumour;carcinoma in situ (CIS);  Multiple, recurrent and large (> 3 cm)\r\n             TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)\r\n\r\n          -  Tumors of T2 stage or more serious\r\n\r\n          -  The histological types are mainly non-urothelial carcinomas such as squamous cell\r\n             carcinoma and adenocarcinoma\r\n\r\n          -  Urothelial carcinoma outside the bladder (renal pelvis, ureter or urethra)\r\n\r\n          -  Received intravesical therapy in last TURBT/cystoscopy prior to treatment period, but\r\n             not including immediate intravesical therapy once (the subjects who received the\r\n             immediate intravesical therapy need to be recorded in e-CRF)\r\n\r\n          -  Received surgery (not includes TURBT/cystoscopy), radiation therapy, or systemic\r\n             therapy within 6 weeks before enrollment\r\n\r\n          -  Malignancies within 2 years with exception of currently treated basal cell, squamous\r\n             cell carcinoma of the skin, or carcinoma \"in-situ' of the cervix\r\n\r\n          -  Grade 3 (according to the NCI CTCAE 5.0) hemorrhage in any part of body within 6 weeks\r\n             before starting the treatment of trial\r\n\r\n          -  Any of the following within 6 months prior to study drug administration: myocardial\r\n             infarction, severe/unstable angina, coronary/peripheral artery bypass graft,\r\n             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic\r\n             attack, or pulmonary embolism\r\n\r\n          -  Hypertension that cannot be controlled by medications (systolic blood pressure140\r\n             mmHg and/or diastolic blood pressure90mmHg)\r\n\r\n          -  Uncontrolled active infections before starting the treatment of trial, such as acute\r\n             pneumonia, active hepatitis B, etc.\r\n\r\n          -  Dysphagia or known drug absorption disorders\r\n\r\n          -  Anuria\r\n\r\n          -  One week prior to enrollment, having gross hematuria\r\n\r\n          -  Active duodenal ulcers, ulcerative colitis and other gastrointestinal diseases or\r\n             other conditions that the investigator may determine to cause gastrointestinal\r\n             bleeding or perforation\r\n\r\n          -  The risk of participation or administration may increase, judged by investigator, or\r\n             other severe acute or chronic medical conditions may interfere with the interpretation\r\n             and judgment of results\r\n\r\n          -  or optic nerve disorders\r\n\r\n          -  Subjects have optic nerve disorders and cataracts, or other related medical history\r\n\r\n          -  Pregnancy or breastfeeding. Female patients with reproductive potential have a\r\n             positive pregnancy test prior to enrollment\r\n\r\n          -  Psychological or mental abnormality, subjects are estimated to have insufficient\r\n             adherence to this clinical study\r\n\r\n          -  Four weeks prior to enrollment, participate in other clinical trials\r\n\r\n          -  Patients who had previously received anthracycline for systemic chemotherapy\r\n      ","sponsor":"Jiangsu Yahong Meditech Co., Ltd aka Asieris","sponsor_type":"Industry","conditions":"Non-muscle Invasive Bladder Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: APL-1202","description":"APL-1202 single-agent oral treatment"},{"intervention_type":"Drug","name":"Drug: Epirubicin Hydrochloride","description":"Epirubicin hydrochloride"}],"outcomes":[{"outcome_type":"primary","measure":"Event-free survival (EFS)","time_frame":"Up to 48 months","description":"Event-free survival (EFS) based on the assessment of pathological report from the Independent Pathology Review Committee (IPRC)"},{"outcome_type":"secondary","measure":"Event-free survival (EFS) based on the assessment of pathological report from each site","time_frame":"Up to 48 months","description":"Event-free survival (EFS) based on the assessment of pathological report from each site"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 48 months","description":"Overall survival (OS)"},{"outcome_type":"secondary","measure":"Recurrence-free rate","time_frame":"Up to 48 months","description":"Recurrence-free rate at 12,18, and 24 months after enrollment"},{"outcome_type":"secondary","measure":"Progression-free rate","time_frame":"Up to 48 months","description":"Progression-free rate at 12,18, and 24 months after enrollment"},{"outcome_type":"secondary","measure":"Clinical benefit rates","time_frame":"Up to 48 months","description":"Clinical benefit rates at 12,18, 24 months after enrollment (clinical benefits are defined as the pathological improvement of the recurrence, no high-risk recurrence, progression-free recurrence, no radical therapy and no death)"},{"outcome_type":"secondary","measure":"Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life Total Score","time_frame":"Up to 48 months","description":"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions \"How would you rate your overall health during the past week?\" and \"How would you rate your overall quality of life during the past week?\" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome"},{"outcome_type":"secondary","measure":"Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score","time_frame":"Up to 48 months","description":"The EORTC-QLQ-NMIBC24 is a 24-item questionnaire developed to supplement the EORTC QLQ-C30 in high-risk NMIBC patients. Each item is scored out of 4 total points (1=Not at All to 4=Very Much). All responses are transformed from 0 to 100, with a high score indicating more symptoms or problems. The change from baseline in EORTC-QLQ-NMIBC24 total score will be presented."},{"outcome_type":"other","measure":"Cystectomy-free survival (CFS)","time_frame":"Up to 48 months","description":"Cystectomy-free survival (CFS)"}]}
{"nct_id":"NCT05039177","start_date":"2021-09-30","phase":"Phase 1/Phase 2","enrollment":200,"brief_title":"A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies","official_title":"A Phase 1b/2 Study of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Gastrointestinal Malignancies (HERKULES-3)","primary_completion_date":"2024-08-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-09-14","description":"- To evaluate the safety and tolerability of escalating doses of ERAS-007 in combination with other cancer therapies in study participants with advanced GI malignancies. - To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with other cancer therapies. - To evaluate the antitumor activity of ERAS-007 in combination with other cancer therapies. - To evaluate the PK profiles of ERAS-007 and other cancer therapies when administered in combination.","other_id":"ERAS-007-03","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":99,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Age  18 years.\r\n\r\n          -  Willing and able to give written informed consent.\r\n\r\n          -  Have histologically or cytologically confirmed metastatic CRC harboring applicable\r\n             mutation(s) (e.g., BRAF V600E; KRAS or NRAS mutations) based on an analytically\r\n             validated assay performed on tumor tissue in a certified testing laboratory.\r\n\r\n          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\r\n\r\n          -  Adequate bone marrow and organ function.\r\n\r\n          -  Have ECOG performance status of 0 or 1.\r\n\r\n          -  Willing to comply with all protocol-required visits, assessments, and procedures.\r\n\r\n          -  Able to swallow oral medication.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior therapy with a RAS, MEK, or ERK inhibitor. Depending on which treatment arm the\r\n             patient is assigned, other therapies could also be prohibitive.\r\n\r\n          -  Anti-cancer therapy  21 days or 4 half-lives prior to first dose of study drug,\r\n             whichever is shorter.\r\n\r\n          -  Palliative radiation  7 days prior to first dose of study drug.\r\n\r\n          -  Symptomatic brain metastasis or leptomeningeal disease.\r\n\r\n          -  Gastrointestinal conditions that may affect absorption of oral medications\r\n\r\n          -  Active infection requiring systemic therapy, or history of HIV infection, hepatitis B\r\n             virus, or hepatitis C virus.\r\n\r\n          -  History of chronic inflammatory bowel disease or Crohn's disease requiring medical\r\n             intervention (immunomodulatory or immunosuppressive medications or surgery)  12\r\n             months prior to first study drug dose.\r\n\r\n          -  Active, clinically significant interstitial lung disease or pneumonitis.\r\n\r\n          -  Impaired cardiovascular function or clinically significant cardiovascular disease.\r\n\r\n          -  History of thromboembolic or cerebrovascular events  6 months prior to first dose.\r\n\r\n          -  Major surgery within 28 days of enrollment, or anticipation of major surgery during\r\n             study treatment.\r\n\r\n          -  Known intolerance or contraindication to encorafenib, cetuximab, or palbociclib.\r\n\r\n          -  Pregnant or breastfeeding women.\r\n\r\n          -  Any evidence of severe or uncontrolled systemic disease or evidence of any other\r\n             significant clinical disorder or laboratory finding that renders the patient\r\n             inappropriate to participate in the study.\r\n      ","sponsor":"Erasca, Inc.","sponsor_type":"Industry","conditions":"Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ERAS-007","description":"Administered orally"},{"intervention_type":"Drug","name":"Drug: Encorafenib","description":"Administered orally"},{"intervention_type":"Drug","name":"Drug: Cetuximab","description":"Administered via intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Palbociclib","description":"Administered orally"}],"outcomes":[{"outcome_type":"secondary","measure":"Plasma concentration (Cmax)","time_frame":"Study Day 1 up to Day 29","description":"Maximum plasma or serum concentration of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Time to achieve Cmax (Tmax)","time_frame":"Study Day 1 up to Day 29","description":"Time to achieve maximum plasma or serum concentration of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Area under the curve","time_frame":"Study Day 1 up to Day 29","description":"Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Half-life","time_frame":"Study Day 1 up to Day 29","description":"Half-life of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Assessed up to 24 months from time of first dose","description":"Based on assessment of radiographic imaging per RECIST version 1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Assessed up to 24 months from time of first dose","description":"Based on assessment of radiographic imaging per RECIST version 1.1"},{"outcome_type":"primary","measure":"Dose Limiting Toxicities (DLT)","time_frame":"Study Day 1 up to Day 29","description":"Based on adverse events observed during dose escalation"},{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD)","time_frame":"Study Day 1 up to Day 29","description":"Based on adverse events observed during dose escalation"},{"outcome_type":"primary","measure":"Recommended Dose (RD)","time_frame":"Study Day 1 up to Day 29","description":"Based on adverse events observed during dose escalation"},{"outcome_type":"primary","measure":"Adverse Events","time_frame":"Assessed up to 24 months from time of first dose","description":"Incidence and severity of treatment-emergent AEs and serious AEs"}]}
{"nct_id":"NCT05033132","start_date":"2021-09-30","phase":"Phase 2","enrollment":160,"brief_title":"A Phase 2 Study of Balstilimab Independently or in Combination With Zalifrelimab in Cervical Cancer","official_title":"A Phase 2 Trial of Balstilimab as a Monotherapy or Combination Therapy With Zalifrelimab in Cervical Cancer","primary_completion_date":"2023-03-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-09-30","last_update":"2021-09-10","description":"This is a randomized, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy ,safety and pharmacokinetics of Balstilimab (Treatment Arm 1 - monotherapy) or in combination with Zalifrelimab (Treatment Arm 2- combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy.","other_id":"C-750-CN01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Voluntarily agree to participate by giving written informed consent.\r\n\r\n          -  Be 18 years of age.\r\n\r\n          -  Diagnosis:\r\n\r\n               1. Have a histologically or cytologically confirmed diagnosis of squamous-cell\r\n                  carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and\r\n                  metastatic, locally advanced, and/or unresectable disease at the time of\r\n                  enrollment.\r\n\r\n                  Note: The following cervical tumors are not eligible: minimal deviation/adenoma\r\n                  malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric\r\n                  carcinoma.\r\n\r\n               2. Has cervical cancer and has relapsed after a platinum based treatment (first\r\n                  line) regimen for advanced (recurrent, unresectable, or metastatic) disease;\r\n\r\n               3. PD-L1 positive(CPS1).\r\n\r\n          -  Have measurable disease on imaging based on RECIST version 1.1.\r\n\r\n          -  Have a life expectancy of at least 3 months.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Have adequate organ function as indicated by the following laboratory values:\r\n\r\n               1. Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5\r\n                  x 10^9/L, platelet count > 100 x 10^9/L, and hemoglobin >8 g/dL (without\r\n                  transfusions within 1 week of first dose).\r\n\r\n               2. Adequate hepatic function based by a total bilirubin level  1.5 the\r\n                  institutional upper limit of normal (ULN), aspartate aminotransferase (AST) level\r\n                   2.5 x ULN, alanine aminotransferase (ALT) level  2.5 x ULN, and alkaline\r\n                  phosphatase  2.5 x ULN.\r\n\r\n               3. Adequate renal function defined as creatinine  1.5  upper limit of normal (ULN)\r\n                  OR measured and calculated creatinine clearance 50 mL/minute per Institutional\r\n                  standard.\r\n\r\n               4. Adequate coagulation defined by international normalized ratio (INR) or\r\n                  prothrombin time  1.5 x ULN (unless the patient is receiving anticoagulant\r\n                  therapy); and activated partial thromboplastin time (aPTT)  1.5 x ULN (unless\r\n                  the patient is receiving anticoagulant therapy).\r\n\r\n          -  Has no history of another primary malignancy with no known active disease 5 years\r\n             before the first dose of study drug, with the exception of adequately treated\r\n             non-melanoma skin cancer , lentigo maligna or superficial bladder cancer.\r\n\r\n          -  Patients must provide a sufficient and adequate FFPE tumor tissue sample preferably\r\n             from the most recent biopsy of a tumor lesion, collected either at the time of or\r\n             after the diagnosis of advanced or metastatic disease has been made AND from a site\r\n             not previously irradiated. If no tumor tissue is available, a fresh biopsy will be\r\n             required.\r\n\r\n          -  Patients must have a negative serum pregnancy test at screening (within 7 days of\r\n             first dose of study medication) if of childbearing potential or be of non-child\r\n             bearing potential. Non-childbearing potential is defined as (by other than medical\r\n             reasons):\r\n\r\n               1. 45 years of age and has not had menses for greater than 1 year,\r\n\r\n               2. Amenorrheic  2 years without a hysterectomy and oophorectomy and a\r\n                  follicle-stimulating hormone (FSH) value in the postmenopausal range upon\r\n                  pretrial (screening) evaluation,\r\n\r\n               3. History of hysterectomy, oophorectomy or tubal ligation.\r\n\r\n          -  If of childbearing potential, female patients must be willing to use adequate barrier\r\n             methods throughout the study, starting with the screening visit through 12 months\r\n             after the last dose of study treatment.\r\n\r\n          -  Is willing and able to comply with the requirements of the protocol.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Is currently participating and receiving study therapy or has participated in a study\r\n             of an investigational agent and received study therapy or used an investigation device\r\n             within 4 weeks of the first dose of treatment.\r\n\r\n          -  Has an inadequate washout period prior to first dose of study drug defined as:\r\n\r\n               1. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks\r\n                  before first dose, or,\r\n\r\n               2. Received radiation therapy within 3 weeks before first dose, or,\r\n\r\n               3. Had major surgery within 4 weeks before first dose.\r\n\r\n          -  Has received prior therapy with Any antibody/drug targeting T-cell co-regulatory\r\n             proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, anti-cytotoxic\r\n             T-lymphocyte antigen 4 (CTLA-4) antibodies or Lag3.\r\n\r\n          -  Is expected to require any other form of systemic or localized antineoplastic therapy\r\n             while on trial (including maintenance therapy with another agent, radiation therapy,\r\n             and/or surgical resection).\r\n\r\n          -  Has known severe hypersensitivity reactions to fully human monoclonal antibodies\r\n             (NCI-CTCAE Grade 3).\r\n\r\n          -  Received hematopoietic stimulating factor treatment within 7 days ( 7 days) before\r\n             the first dose, such as granulocyte colony stimulating factor (G-CSF), erythropoietin,\r\n             etc.\r\n\r\n          -  Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous\r\n             meningitis identified either on the baseline brain imaging obtained during the\r\n             screening period OR identified prior to consent.\r\n\r\n        Note: Patients with history of brain metastases that have been treated may participate\r\n        provided they show evidence of stable supra-tentorial lesions at screening (based on 2 sets\r\n        of brain images, performed  4 weeks apart, and obtained after the brain metastases\r\n        treatment). In addition, any neurologic symptoms that developed either as a result of the\r\n        brain metastases or their treatment must have resolved or be minimal and be expected as\r\n        sequelae from treated lesions. For individuals who received steroids as part of brain\r\n        metastases treatment, steroids must be discontinued  7 days prior to first dose of study\r\n        drug.\r\n\r\n        -Has active or history of autoimmune disease that has required immunosuppressive systemic\r\n        treatment within 2 years of the start of trial treatment (i.e. with use of disease\r\n        modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e.,\r\n        thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or\r\n        pituitary insufficiency, etc.) is not considered a form of immunosuppressive systemic\r\n        treatment.\r\n\r\n        Note: Patients with diabetes type 1, vitiligo, psoriasis, hypothyroidism, or hyperthyroid\r\n        disease not requiring immunosuppressive treatment are eligible.\r\n\r\n          -  Has had an allogeneic tissue/solid organ transplant.\r\n\r\n          -  Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that\r\n             has required oral or intravenous corticosteroids.\r\n\r\n          -  Has an active infection requiring intravenous systemic therapy.\r\n\r\n          -  Has known history of Human Immunodeficiency Virus (HIV) or treponema pallidum.\r\n\r\n          -  Has known active Hepatitis B (HBV), Hepatitis C (HCV), or tuberculosis.Active\r\n             Hepatitis B is defined as a known positive HBsAg or HBcAb result. Active Hepatitis C\r\n             is defined by a known positive Hep C Ab result and known quantitative HCV ribonucleic\r\n             acid (RNA) results greater than the lower limits of detection of the assay.\r\n\r\n          -  Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular\r\n             accident/stroke or myocardial infarction within 6 months of enrollment, unstable\r\n             angina, congestive heart failure (New York Heart Association class II), or serious\r\n             uncontrolled cardiac arrhythmia requiring medication, cerebrovascular accident,\r\n             transient ischemic attack, cerebral embolism.\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the trial, interfere with the patient's\r\n             participation for the full duration of the trial, or is not in the best interest of\r\n             the patient to participate, in the opinion of the treating investigator.\r\n\r\n          -  Has known psychiatric that would interfere with cooperation with the requirements of\r\n             the trial.\r\n\r\n          -  Has a history of substance abuse, alcoholism or other addictions.\r\n\r\n          -  Is legally incapacitated or has limited legal capacity.\r\n      ","sponsor":"Agenus Inc.","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Balstilimab","description":"Anti-programmed cell death protein 1 (Anti-PD-1) antibody monoclonal antibody"},{"intervention_type":"Drug","name":"Drug: Balstilimab + Zalifrelimab","description":"A PD-1 antibody in combination with a CTLA-4 antibody."}],"outcomes":[{"outcome_type":"primary","measure":"Frequency, severity and duration of treatment-emergent AEs","time_frame":"36 months"},{"outcome_type":"primary","measure":"Objective Response Rate","time_frame":"18 months"}]}
{"nct_id":"NCT05031494","start_date":"2021-09-30","phase":"Phase 2","enrollment":129,"brief_title":"A Study to Assess YH003 in Combination With Toripalimab(Anti-PD-1 mAb) Injection in Patients With Cancers","official_title":"A Multi-center, Open-label Phase II Study to Evaluate the Safety and Efficacy of YH003 in Combination With Toripalimab (Anti-PD-1 mAb) in Patients With Unresectable/Metastatic Melanoma and Pancreatic Ductal Adenocarcinoma (PDAC)","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-12-31","last_update":"2021-09-02","description":"A phase II, multi-center, open-label study to evaluate the safety and efficacy of YH003 in combination with Toripalimab (anti-PD-1 mAb) in patients with unresectable/metastatic melanoma and pancreatic ductal adenocarcinoma (PDAC)","other_id":"YH003004","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  To be eligible for study entry patients must satisfy all of the following criteria:\r\n\r\n          -  1. Subjects must have the ability to understand and willingness to sign a written\r\n             informed consent document.\r\n\r\n          -  2. Histologically or cytologically confirmed unresectable or metastatic melanoma and\r\n             pancreatic ductal adenocarcinoma\r\n\r\n          -  Cohort 2A: had confirmed progressive disease during treatment with an anti-PD-1/PD-L1\r\n             with or without CTLA-4 therapy.\r\n\r\n          -  Cohort 2B: had confirmed progressive disease during treatment with first line standard\r\n             of care chemotherapy per local guideline.\r\n\r\n          -  Cohort 2C: must not have received any prior systematic treatment, including\r\n             chemotherapy, biological therapy, or targeted therapy for unresectable locally\r\n             advanced/ metastatic pancreatic duct adenocarcinoma.\r\n\r\n          -  3. Subject must have at least 1 unidimensional measurable disease by RECIST 1.1.\r\n\r\n          -  4. Subjects must be age between 18 years.\r\n\r\n          -  5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status\r\n             of 0 or 1.\r\n\r\n          -  6. Life expectancy 3 months.\r\n\r\n          -  7. Subjects must have adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects who meet any of the following criteria cannot be enrolled:\r\n\r\n          -  1. Cohort 2A: History of life-threatening toxicity or treatment discontinuation due to\r\n             related to prior anti-PD-1/PD-L1 with or without CTLA-4 treatment for subjects with\r\n             unresectable/ metastatic melanoma\r\n\r\n          -  2.Subjects have another active invasive malignancy within 5 years, with the following\r\n             exceptions and notes:\r\n\r\n          -  3. Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.\r\n\r\n          -  4. Subjects must not have received any anticancer therapy or another investigational\r\n             agent within the shorter of 4 weeks or 5 half-lives before the first dose of the study\r\n             treatment.\r\n\r\n          -  5. Subjects with a history of  Grade 3 immune-related adverse events resulted from\r\n             previous immunotherapy or treatment discontinuation due to previous immunotherapy. .\r\n\r\n          -  6. History of clinically significant sensitivity or allergy to monoclonal antibodies\r\n             and their excipients or known allergies to antibodies produced from Chinese hamster\r\n             ovary cells, which in the opinion of the Investigator suggests an increased potential\r\n             for an adverse hypersensitivity to YH003 or Toripalimab. (For cohort 2C: history of\r\n             severe hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine).\r\n\r\n          -  7. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.\r\n\r\n          -  8. History of (non-infectious) pneumonitis that required corticosteroids or current\r\n             pneumonitis, or history of interstitial lung disease.\r\n\r\n          -  9. Active, hemodynamically significant pulmonary embolism within 12 weeks prior to the\r\n             first dose of study drug.\r\n\r\n          -  10. Subjects must not have a known or suspected history of an autoimmune disorder\r\n\r\n          -  11. Clinically uncontrolled intercurrent illness,\r\n\r\n          -  12. Severe cardiovascular disease including symptomatic congestive heart failure (New\r\n             York Heart Association class III or IV), unstable angina, uncontrolled hypertension,\r\n             cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of\r\n             arterial thromboembolic event and pulmonary embolism within 3 months of the first dose\r\n             of investigational agent.\r\n\r\n          -  13. QTc > 480 ms (Fridericia equation) at baseline; no concomitant medications that\r\n             would prolong the QT interval; no family history of long QT syndrome.\r\n      ","sponsor":"Eucure (Beijing) Biopharma Co., Ltd","sponsor_type":"Industry","conditions":"Melanoma|Pancreatic Ductal Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: YH003","description":"YH003 will be dosed at 0.3 mg/kg every 3 weeks. The first infusion of YH003 should be administered over 60 minutes."},{"intervention_type":"Drug","name":"Drug: Toripalimab","description":"Toripalimab will be administered at a dose of 240 mg every 3 weeks."},{"intervention_type":"Drug","name":"Drug: Nab-paclitaxel","description":"Nab-paclitaxel will be administered each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Gemcitabine will be administrated each 21-day cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"up to 1 year after the last dosing","description":"Overall Response Rate (ORR) by investigator's assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1"},{"outcome_type":"secondary","measure":"Adverse events (AE)","time_frame":"up to 1 year after the last dosing","description":"The safety profile of YH003 in combination with Toripalimab will be assessed by monitoring the adverse events (AE) per NCI CTCAE v5.0"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Time to response (TTR)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Duration of disease control (DDC)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"up to 1 year after the last dosing","description":"To assess the antitumor activity of YH003 in combination with Toripalimab"},{"outcome_type":"secondary","measure":"Incidence of neutralizing antibodies (NAbs)","time_frame":"up to 1 year after the last dosing","description":"To assess the immunogenicity of YH003 in combination with Toripalimab"}]}
{"nct_id":"NCT05014815","start_date":"2021-09-30","phase":"Phase 2","enrollment":200,"brief_title":"Ociperlimab With Tislelizumab and Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer","official_title":"A Phase 2, Randomized, Double-blind Study of Ociperlimab (BGB A1217) and Tislelizumab With Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Without Sensitizing EGFR or ALK Mutations Who Have Received No Previous Treatment for Metastatic Disease","primary_completion_date":"2023-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-30","last_update":"2021-08-20","description":"This study will evaluate the safety and efficacy of ociperlimab with tislelizumab and chemotherapy compared with treatment with tislelizumab and chemotherapy in participants with metastatic non-small cell lung cancer (NSCLC)","other_id":"AdvanTIG-205","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          1. Histologically confirmed metastatic (Stage IV) squamous or non-squamous NSCLC.\r\n\r\n          2. Treatment-naive for metastatic squamous or non-squamous NSCLC.\r\n\r\n          3. Agreement to provide archival tissue or fresh biopsy for the prospectively\r\n             determination of PD-L1 levels and retrospective analysis of other biomarkers.\r\n\r\n          4. At least 1 measurable lesion as defined per RECIST v1.1.\r\n\r\n             .\r\n\r\n          5. Eastern Cooperative Oncology Group (ECOG) Performance Status  1.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          1. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation or ALK gene\r\n             translocation.\r\n\r\n          2. Prior therapy with an anti-programmed cell death protein (PD-1), anti-PD-L1,\r\n             anti-programmed cell death ligand-2 (PD-L2), anti-TIGIT, or any other antibody or drug\r\n             specifically targeting T-cell costimulation or checkpoint pathways.\r\n\r\n          3. Active leptomeningeal disease or uncontrolled, untreated brain metastasis.\r\n\r\n          4. Any active malignancy  2 years before randomization except for the specific cancer\r\n             under investigation in this study and any locally recurring cancer that has been\r\n             treated curatively (for example, resected basal or squamous cell skin cancer,\r\n             superficial bladder cancer, carcinoma in situ of the cervix or breast).\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Tislelizumab","description":"Tislelizumab intravenous injection"},{"intervention_type":"Drug","name":"Drug: Ociperlimab","description":"Ociperlimab intravenous injection"},{"intervention_type":"Drug","name":"Drug: histology-based chemotherapy","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Administered as an intravenous injection"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free Survival (PFS) as Assessed by Investigators","time_frame":"Up to approximately 30 months","description":"PFS will be defined as the time from the date of randomization to the date of the first objectively documented tumor progression per RECIST v1.1, or death, whichever occurs first"},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR) as Assessed by Investigators","time_frame":"Up to approximately 30 months","description":"ORR will be defined as the proportion of participants with a documented, confirmed complete response or partial response per RECIST v1.1."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 30 months","description":"OS will be defined as the time from the date of randomization to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Number of Participants Experiencing Adverse Events (AEs)","time_frame":"90 days (±14) after last dose","description":"The incidence and severity of AEs will be determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)."},{"outcome_type":"secondary","measure":"Serum concentrations of ociperlimab and tislelizumab at prespecified timepoints","time_frame":"Up to approximately 12 months or end of treatment visit"},{"outcome_type":"secondary","measure":"Immunogenic responses to ociperlimab and tislelizumab, evaluated through detection of anti-drug antibodies (ADAs).","time_frame":"Up to approximately 12 months or end of treatment visit"}]}
{"nct_id":"NCT05010759","start_date":"2021-09-30","phase":"N/A","enrollment":200,"brief_title":"Study of Focal Ablation of the Prostate With NanoTherm Therapy System for Intermediate-Risk Prostate Cancer","official_title":"Stage 3 of: A Pivotal, Prospective, Three-Stage, Single-Arm Study of Focal Ablation of the Prostate With NanoTherm Therapy System for a Limited-Volume, Clinically Localized, Intermediate-Risk Prostate Cancer","primary_completion_date":"2022-02-28","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-10-31","last_update":"2021-09-13","description":"Stage 3: NanoTherm ablation of focal prostate cancer in small lesions in Gleason 3+3 and Clean 3+4 disease. The outcome of this ablation is validated by a transperineal biopsy at 4 months after ablation.","other_id":"MGF-0115 - Stage 3","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":40,"maximum_age":85,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Age 40 to 85\r\n\r\n          -  Male\r\n\r\n          -  Prostate adenocarcinoma on biopsy\r\n\r\n          -  Clinical stage T1c/T2a/T2b, N0, M0/Mx with no lesion larger than 2cc in volume\r\n\r\n          -  The following biopsy findings (biopsy must have MRI visualization and be within 6\r\n             months of planned NanoTherm treatment):\r\n\r\n               -  A positive biopsy for prostate cancer from the MRI-visualized lesion, at least\r\n                  one of which must be Gleason 3+3 (up to 50 subjects) or 3+4 (grade group 2)\r\n\r\n          -  Lesion must be visualized by Multiparametric Magnetic Resonance Imaging (MP-MRI) on a\r\n             scan that is less than 6 months old\r\n\r\n          -  Patient expresses a preference for active surveillance, rather than surgery or\r\n             radiation, to manage prostate cancer\r\n\r\n          -  Based on the evaluation of the study investigator, appropriate for instillation of\r\n             NanoTherm under anesthesia based on location and size of the clinical target volume\r\n             (CTV)\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previous treatment for cancer with radiation, androgen deprivation (including\r\n             LHRH-agonists or antagonists or antiandrogens), or surgery for prostate cancer\r\n\r\n          -  Active urinary tract infection\r\n\r\n          -  Metallic implants below the neck\r\n\r\n          -  Gleason 3+4 or higher cancer on prostate biopsy outside of the planned CTV\r\n\r\n          -  Gleason 4+3 or higher on any prostate biopsy\r\n\r\n          -  Hematological abnormality indicating increased risk of bleeding or clotting, for\r\n             example low platelet count or anemia\r\n\r\n          -  Participation concurrently in another clinical trial for prostate disease or in the\r\n             last 30 days\r\n\r\n          -  Known hypersensitivity to Axumin\r\n      ","sponsor":"MagForce USA","sponsor_type":"Industry","conditions":"Prostate Cancer","interventions":[{"intervention_type":"Device","name":"Device: NanoTherm Ablation","description":"Iron nanoparticles are instilled into the prostate cancer lesion and then the particles are heated using a magnetic field and this heating ablates the prostate cancer lesion."}],"outcomes":[{"outcome_type":"primary","measure":"Rate of Ablation Success","time_frame":"4 months (+/- 1 Month)","description":"Rate of subjects with a biopsy confirmed ablation of prostate cancer lesion"},{"outcome_type":"secondary","measure":"Adverse Event Rate","time_frame":"4 months (+/- 1 Month)","description":"Rate of Adverse Events of Special Interest (AESI)"}]}
{"nct_id":"NCT05008510","start_date":"2021-09-30","phase":"Phase 2","enrollment":216,"brief_title":"P2 Clinical Efficacy & Safety Study of V-111 Monotherapy & Sacituzumab Govitecan-hziy/V-111 Combo Therapy for mTNBC .","official_title":"Phase 2 Clinical Efficacy and Safety Study of Sabizabulin (VERU-111) Monotherapy and Sacituzumab Govitecan-hziy/Sabizabulin Combination Therapy for the Treatment of Metastatic Triple Negative Breast Cancer","primary_completion_date":"2022-07-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-06-30","last_update":"2021-08-17","description":"To compare the following: 1. The efficacy of sabizabulin monotherapy to sacituzumab govitecan-hziy monotherapy 2. The efficacy of sacituzumab govitecan-hziy/sabizabulin combination therapy to sacituzumab govitecan-hziy monotherapy These comparisons will be made in the efficacy in the treatment of metastatic triple negative breast cancer (mTNBC) in patients previously treated with at least two systemic chemotherapies for metastatic disease as measured by radiographic progression free survival (rPFS) as the primary endpoint.","other_id":"V2011801","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Single","intervention_model_description":"This study is a multicenter, randomized, open-label, three treatment-arm, efficacy and safety study. Subjects will be randomized to the three treatment arms.","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":100,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Provide informed consent\r\n\r\n          -  Be able to communicate effectively with the study personnel\r\n\r\n          -  Aged 18 years\r\n\r\n          -  For Female Subjects\r\n\r\n          -  Menopausal status Be postmenopausal as defined by the National Comprehensive Cancer\r\n\r\n        Network as either:\r\n\r\n          -  Age 55 years and one year or more of amenorrhea\r\n\r\n          -  Age <55 years and one year or more of amenorrhea, with an estradiol assay <20 pg/mL\r\n\r\n          -  Age <55 years and surgical menopause with bilateral oophorectomy Be premenopausal or\r\n             perimenopausal with a negative urine pregnancy test. If subject is of child-bearing\r\n             potential, the subject must agree to use acceptable methods of contraception:\r\n\r\n          -  If female study participant could become pregnant, use acceptable methods of\r\n             contraception from the time of the first administration of study medication until 6\r\n             months following administration of the last dose of study medication. Acceptable\r\n             methods of contraception are as follows: Condom with spermicidal\r\n             foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical\r\n             sterilization of male partner (vasectomy with documentation of azoospermia) and a\r\n             barrier method {condom used with spermicidal foam/gel/film/cream/suppository}\r\n\r\n          -  If female study participant has undergone documented tubal ligation (female\r\n             sterilization), a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  If female study participant has undergone documented placement of an intrauterine\r\n             device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal\r\n             foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  For Male Subjects\r\n\r\n          -  Subject must agree to use acceptable methods of contraception:\r\n\r\n        If the study subject's partner could become pregnant, use acceptable methods of\r\n        contraception from the time of the first administration of study medication until 6 months\r\n        following administration of the last dose of study medication. Acceptable methods of\r\n        contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository\r\n        [i.e., barrier method of contraception], surgical sterilization (vasectomy with\r\n        documentation of azoospermia) and a barrier method {condom used with spermicidal\r\n        foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination\r\n        estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier\r\n        method (condom used with spermicidal foam/gel/film/cream/suppository)\r\n\r\n          -  If female partner of a study subject has undergone documented tubal ligation (female\r\n             sterilization), a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  If female partner of a study subject has undergone documented placement of an\r\n             intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with\r\n             spermicidal foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  If female partner of a study subject has undergone documented placement of an\r\n             intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with\r\n             spermicidal foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2\r\n\r\n          -  Histologically or cytologically confirmed TNBC based on the most recent analyzed\r\n             biopsy or other pathology specimen. Triple negative defined as <1% expression for\r\n             estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal\r\n             growth factor receptor 2 (HER2) by in-situ hybridization.\r\n\r\n          -  Measurable disease is required as per RECIST 1.1 confirmed by BICR (NOTE: Bone only\r\n             metastatic disease is acceptable but requires a measurable component).\r\n\r\n          -  Refractory to or relapsed after at least two prior standard chemotherapy regimens for\r\n             advanced/metastatic TNBC and have not received Sacituzumab govitecan-hziy.\r\n\r\n          -  At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, radiotherapy,\r\n             and/or major surgery), and recovered from all acute toxicities to Grade 1 or less\r\n             (except alopecia and peripheral neuropathy).\r\n\r\n          -  At least 2 weeks beyond high dose systemic corticosteroids (however, low dose\r\n             corticosteroids < 20 mg prednisone or equivalent daily are permitted).\r\n\r\n          -  Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC >\r\n             1,500 per mm3, platelets > 100,000 per mm3).\r\n\r\n          -  Adverse events at study entry < Grade 1 by NCI CTCAE v5.0 (Patients with  Grade 2\r\n             neuropathy and any grade of alopecia are eligible).\r\n\r\n          -  Patients with treated, non-progressive brain metastases, off high-dose steroids (>20\r\n             mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.\r\n\r\n          -  Subject is willing to comply with the requirements of the protocol through the end of\r\n             the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Women who are pregnant or lactating\r\n\r\n          -  Women of childbearing potential or fertile men with a female partner of childbearing\r\n             potential not willing to use effective contraction during the study and 6 months after\r\n             last dose of study drug for the women of childbearing potential participating in the\r\n             study and for 3 months after last dose of study drug in fertile men with a female\r\n             partner of childbearing potential.\r\n\r\n          -  Known hypersensitivity or allergy to sabizabulin or Sacituzumab govitecan-hziy\r\n\r\n          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 X upper limit\r\n             of normal (ULN) or total bilirubin >ULN (an elevated total bilirubin up to 1.5 X ULN\r\n             attributed to a previously confirmed diagnosis of Gilbert's disease is acceptable if\r\n             all other eligibility criteria are met). In patients with documented metastases to the\r\n             liver, the limits for inclusion are ALT or AST >5.0 X ULN or total bilirubin >1.5 X\r\n             ULN.\r\n\r\n          -  Patients with biliary catheter\r\n\r\n          -  Creatinine Clearance 60 mL/min by the Cockroft-Gault equation\r\n\r\n          -  Has a known additional, invasive, malignancy that is progressing or required active\r\n             treatment in the last 5 years (note: subjects with basal cell carcinoma of the skin,\r\n             squamous cell carcinoma of the skin, superficial bladder cancer, or cervical carcinoma\r\n             in situ that have undergone potentially curative therapy are not excluded)\r\n\r\n          -  Any comorbid disease or condition (medical or surgical) which might compromise the\r\n             hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic,\r\n             or central nervous system; or other conditions that may interfere with the absorption,\r\n             distribution, metabolism or excretion of study drug, or would place the subject at\r\n             increased risk\r\n\r\n          -  Infection requiring antibiotic use within one week or randomization or uncontrolled\r\n             infection.\r\n\r\n          -  Treatment with any investigational product within < 4 half-lives for each individual\r\n             investigational product OR within 28 days prior to randomization\r\n\r\n          -  Pregnant, lactating, or breastfeeding, or intending to become pregnant during the\r\n             study or within 60 days after the final dose of study treatment\r\n      ","sponsor":"Veru Inc.","sponsor_type":"Industry","conditions":"Metastatic Triple Negative Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Sabizabulin","description":"Sabizabulin (Veru-111)"},{"intervention_type":"Drug","name":"Drug: Sacituzumab Govitecan-hziy","description":"Sacituzumab govitecan-hziy"},{"intervention_type":"Drug","name":"Drug: Sabizabulin/Sacituzumab govitecan-hziy Combo","description":"Sabizabulin/Sacituzumab govitecan-hziy Combo therpy"}],"outcomes":[{"outcome_type":"primary","measure":"To compare the efficacy of sabizabulin monotherapy to Sacituzumab govitecan-hziy monotherapy","time_frame":"360 days","description":"The comparison will be made in the efficacy in the treatment of metastatic triple negative breast cancer (mTNBC) in patients previously treated with at least two systemic chemotherapies for metastatic disease as measured by radiographic progression free survival (rPFS) as the primary endpoint."},{"outcome_type":"primary","measure":"To compare the efficacy of Sacituzumab govitecan-hziy/sabizabulin combination therapy to Sacituzumab govitecan-hziy monotherapy","time_frame":"360 days","description":"The comparison will be made in the efficacy in the treatment of metastatic triple negative breast cancer (mTNBC) in patients previously treated with at least two systemic chemotherapies for metastatic disease as measured by radiographic progression free survival (rPFS) as the primary endpoint."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR), proportion of subjects with a best tumor response of ORR (PR or CR) on study","time_frame":"360 days","description":"Objective Response Rate (ORR), proportion of subjects with a best tumor response of ORR (PR or CR) on study"}]}
{"nct_id":"NCT04993677","start_date":"2021-09-30","phase":"Phase 2","enrollment":200,"brief_title":"A Study of SEA-CD40 Given With Other Drugs in Cancers","official_title":"An Open-label, Phase 2 Basket Study of SEA-CD40 Combination Therapies in Advanced Malignancies","primary_completion_date":"2024-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-10-31","last_update":"2021-09-14","description":"This trial is being done to see if an experimental drug (SEA-CD40) works when it's given with other cancer drugs to treat some types of cancer. It will also study side effects from the drug. There are 2 parts in this trial. In one part, participants have melanoma that has come back after treatment or can't be removed by surgery. Participants in this part will get SEA-CD40 and pembrolizumab. In the other part, participants have non-small cell lung cancer (NSCLC) that has spread through their body. These participants will get SEA-CD40, pembrolizumab, carboplatin, and pemetrexed.","other_id":"SGNS40-002","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed unresectable malignancy defined as one of\r\n             the following:\r\n\r\n               -  Cohort 1: Relapsed and/or refractory metastatic melanoma\r\n\r\n                    -  Uveal/ocular melanoma is excluded\r\n\r\n                    -  Must have progressed on treatment with an anti-PD-(L)1 mAb. PD-(L)1\r\n                       treatment progression is defined as meeting all of the following criteria:\r\n\r\n          -  Has received at least 2 doses of an approved anti-PD-(L)1 mAb\r\n\r\n          -  Has demonstrated disease progression after PD-(L)1 as defined by RECIST v1.1.\r\n\r\n          -  Progressive disease has been documented within 12 weeks from the last dose of anti-\r\n             PD-(L)1 mAb\r\n\r\n          -  Last dose of anti-PD-(L)1 must have been within 90 days prior to enrollment\r\n\r\n               -  Cohort 2: Metastatic uveal melanoma\r\n\r\n                    -  Must not have received prior treatment for advanced or metastatic disease\r\n                       except for prior adjuvant/neoadjuvant immunotherapy\r\n\r\n                    -  No prior regional, liver-directed therapy\r\n\r\n               -  Cohort 3: Metastatic PD-(L)1-nave melanoma\r\n\r\n                    -  Uveal/ocular melanoma is excluded\r\n\r\n                    -  Must not have received prior treatment for advanced or metastatic disease\r\n                       except for prior adjuvant/neoadjuvant immunotherapy.\r\n\r\n                    -  Participants with BRAF mutation, prior BRAF/MEK targeted therapy is allowed\r\n                       if completed 4 weeks prior to first dose of study treatment.\r\n\r\n               -  Cohorts 4 and 5: Non-squamous NSCLC\r\n\r\n                    -  Participants must have stage IV disease per AJCC 8th edition\r\n\r\n                    -  No known driver mutations/alterations mutation for which targeted therapy is\r\n                       available\r\n\r\n                    -  Must have non-squamous histology.\r\n\r\n                    -  No prior therapy for metastatic disease\r\n\r\n                    -  No prior treatment with anti-PD-(L)1 or PD-L2 agent or an antibody targeting\r\n                       other immuno-regulatory receptors or mechanisms\r\n\r\n          -  Able to provide archival tumor tissue from locations not radiated prior to biopsy\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1\r\n\r\n          -  Measurable disease per RECIST v1.1 at baseline\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of another malignancy within 3 years of first dose of study drug\r\n\r\n          -  Active central nervous system (CNS) metastases and/or carcinomatous meningitis.\r\n\r\n          -  Previous exposure to CD40-targeted therapy\r\n\r\n          -  Currently on chronic systemic steroids in excess of physiologic replacement\r\n\r\n          -  Has had an allogeneic tissue/solid organ transplant.\r\n\r\n          -  History of autoimmune disease that has required systemic treatment in the past 2 years\r\n      ","sponsor":"Seagen Inc.","sponsor_type":"Industry","conditions":"Melanoma|Carcinoma, Non-Small- Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: SEA-CD40","description":"Given into the vein (IV; intravenously); schedule is cohort-specific"},{"intervention_type":"Drug","name":"Drug: pembrolizumab","description":"Given by IV; schedule is cohort-specific."},{"intervention_type":"Drug","name":"Drug: pemetrexed","description":"Given by IV on Day 1 of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: carboplatin","description":"Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long."}],"outcomes":[{"outcome_type":"secondary","measure":"Incidence of dose alterations","time_frame":"Duration of treatment, approximately 2 years","description":"To be summarized using descriptive statistics"},{"outcome_type":"primary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"Duration of treatment, approximately 2 years","description":"The proportion of subjects who achieve a confirmed complete response (CR) or partial (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator."},{"outcome_type":"secondary","measure":"Incidence of adverse events (AEs)","time_frame":"From start of treatment to 30-37 days after last dose, approximately 2 years","description":"Any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment."},{"outcome_type":"secondary","measure":"Incidence of laboratory abnormalities","time_frame":"From start of treatment to 30-37 days after last dose, approximately 2 years","description":"To be summarized using descriptive statistics"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) per investigator assessment","time_frame":"From start of treatment until completion of response assessment, approximately 4 years","description":"The proportion of subjects who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks."},{"outcome_type":"secondary","measure":"Duration of response (DOR) per investigator assessment","time_frame":"From start of treatment until completion of response assessment, approximately 4 years","description":"The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or death due to any cause"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) per investigator assessment","time_frame":"From start of treatment until completion of response assessment, approximately 4 years","description":"The time from the start of study treatment to the first documentation of PD by RECIST v1.1 or death due to any cause"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Duration of study, approximately 4 years","description":"The time from the start of study treatment to date of death due to any cause"}]}
{"nct_id":"NCT04983550","start_date":"2021-09-30","phase":"Phase 2","enrollment":126,"brief_title":"Efficacy and Safety of SG001 Combined With PLD in Patients With Platinum-resistant Relapsed EOC","official_title":"A Multicenter, Randomized, Controlled, Open-label, Phase II Study to Evaluate the Efficacy and Safety of SG001 in Combination With PLD in Patients With Platinum-resistant Relapsed Epithelial Ovarian Cancer","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-01-31","last_update":"2021-07-30","description":"This study is a multicenter, randomized, controlled, open-label, phase II study to evaluate the efficacy and safety of SG001 in combination with doxorubicin hydrochloride liposome injection in patients with platinum-resistant relapsed epithelial ovarian cancer.","other_id":"SYSA1802-CSP-003","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Female patients aged 18-75 (inclusive) years old (based on the day of signing the\r\n             informed consent).\r\n\r\n          2. Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or\r\n             peritoneal, FIGO stage II-IV (per FIGO 2014).\r\n\r\n          3. Patients with platinum-resistant relapse (defined as disease progression within 6\r\n             months after the last platinum-containing chemotherapy) and non-platinum refractory\r\n             (defined as disease progression within 4 weeks after the first platinum-containing\r\n             chemotherapy). Previously received up to three lines of platinum-containing system\r\n             chemotherapy and up to two lines of platinum-free system chemotherapy.\r\n\r\n          4. Patients must provide sufficient qualified FFPE tumor tissue specimens or sections for\r\n             PD-L1 detection.\r\n\r\n          5. At least one measurable lesion per RECIST 1.1 at baseline. Measurable lesions should\r\n             not have received local treatment such as radiotherapy (lesions located within\r\n             previous radiotherapy areas may also be selected as a target lesion if progression is\r\n             confirmed).\r\n\r\n          6. Eastern Cooperative Oncology Group (ECOG) physical status score: 0 or 1.\r\n\r\n          7. Life expectancy 3 months.\r\n\r\n          8. Vital organ function meets the following requirements (no blood transfusion, no use of\r\n             hematopoietic stimulating factor, and no use of medication to correct blood cell count\r\n             within 14 days prior to first administration):\r\n\r\n             A) Absolute neutrophil count (ANC)  1.510^9/L; B) Platelet count (PLT)  7510^9/L;\r\n             C) Hemoglobin (HGB)  9 g/dL; D) Serum creatinine Cr  1.5ULN or creatinine clearance\r\n             Ccr  50 mL/min; E) Total bilirubin (TBil)  1.5ULN (3ULN for patients with\r\n             Gilbert's syndrome); F) Alanine aminotransferase (ALT) and aspartate aminotransferase\r\n             (AST)  2.5ULN ( 5ULN for patients with liver metastasis); G) Activated partial\r\n             thromboplastin time (APTT) and international standardized ratio (INR)  1.5ULN (no\r\n             correction with anticoagulants or other drug affecting coagulation function within 14\r\n             days before the first administration, except long-term anticoagulant therapy is\r\n             needed.).\r\n\r\n          9. Toxic and side effects caused by previous anti-tumor therapy should be restored to 1\r\n             grade (CTCAE 5.0) (except residual alopecia and fatigue) before enrollment.\r\n\r\n         10. Patients are required to give informed consent to this study and voluntarily sign a\r\n             written informed consent prior to the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. A history of severe allergic reaction and uncontrolled allergic asthma to monoclonal\r\n             antibody preparations.\r\n\r\n          2. Untreated known CNS metastases, or treated CNS metastases but still with symptoms\r\n             (except for residual signs or symptoms related to CNS treatment, and those with stable\r\n             or improved neurological symptoms for at least 2 weeks prior to screening can be\r\n             enrolled).\r\n\r\n          3. Patients with a history of primary immunodeficiency.\r\n\r\n          4. Patients with an active autoimmune disease or a history of autoimmune disease, but\r\n             with well-controlled type  diabetes, well-controlled hypothyroidism requiring only\r\n             hormone replacement therapy, skin conditions that do not require general treatment\r\n             (such as vitiligo, psoriasis, or alopecia), or patients whose disease is not expected\r\n             to recur in the absence of external triggers, will be screened for further enrollment.\r\n\r\n          5. Baseline cardiac ejection fraction is less than 50% or the lower limit of normal;\r\n             history of clinically significant prolonged QTc interval (> 450 ms in male, > 470 ms\r\n             in female); cardiac lesions caused by previous use of anthracyclines; serious\r\n             cardiovascular disease, such as New York Heart Association (NYHA) grade 2 or higher\r\n             heart failure, previous myocardial infarction within 3 months, poorly controlled\r\n             arrhythmias, or unstable angina.\r\n\r\n          6. Severe arterial/venous thrombosis events (such as transient ischemic attack, cerebral\r\n             haemorrhage, cerebral infarction, deep venous thrombosis, pulmonary embolism, etc.)\r\n             within 3 months prior to screening.\r\n\r\n          7. Previous interstitial lung disease (except local interstitial pneumonia induced by\r\n             radiotherapy), non-infectious pneumonia requiring glucocorticoid therapy.\r\n\r\n          8. Have received any other antibodies/drugs that act on T cell co-stimulation or\r\n             checkpoint pathways (including PD-1, PD-L1, PD-L2, CTLA-4, OX40, C137 inhibitors,\r\n             etc.).\r\n\r\n          9. Patients with immune related AE CTCAE 5.0 grade score  3 after receiving\r\n             immunotherapy.\r\n\r\n         10. Major surgery or radical radiotherapy within 28 days prior to the first\r\n             administration, or palliative radiotherapy within 14 days prior to the first\r\n             administration, or radiation agents (strontium, samarium, etc.) within 56 days prior\r\n             to the first administration.\r\n\r\n         11. Those who have received systemic antitumor therapy, including but not limited to\r\n             chemotherapy, immunotherapy, macromolecular targeted therapy, or biotherapy (tumor\r\n             vaccines, cytokines, or growth factors for cancer control) within 28 days before the\r\n             first administration of the drug; small molecule targeting and oral fluorouracil-based\r\n             therapy within 14 days (or 5 half-lives, whichever is longer) prior to first\r\n             administration; those who had received mitomycin C and nitrosourea within 6 weeks\r\n             prior to initial administration.\r\n\r\n         12. Those who received live attenuated vaccine within 28 days before the first\r\n             administration or who planned to receive it during the study period.\r\n\r\n         13. Any active infection that requires systemic treatment by intravenous drip within 28\r\n             days prior to first administration.\r\n\r\n         14. Those who have received treatment within 14 days prior to the first dose with a\r\n             proprietary Chinese medicine that has a clear antitumor-related function in the\r\n             NMPA-approved drug specification or a Chinese herbal medicine that is clearly\r\n             documented in the medical record for antitumor purposes.\r\n\r\n         15. Patients who have received whole or component blood transfusion within 14 days prior\r\n             to initial administration.\r\n\r\n         16. Glucocorticoids (prednisone >10 mg/day or equivalent of another similar drug) or other\r\n             immunosuppressive therapy for a condition within 14 days prior to first\r\n             administration.\r\n\r\n         17. Participation in other clinical trials and use of the investigational drug within 28\r\n             days prior to the first administration (counting from the date of the last treatment\r\n             in the previous clinical study) (with the exception of the overall survival follow-up\r\n             period in one study).\r\n\r\n         18. Positive for human immunodeficiency virus (HIV-Ab) and treponema pallidum antibody\r\n             (TP-Ab) antibodies; positive for hepatitis B virus surface antigen (HBsAg) and/or\r\n             hepatitis B core antibody (HBcAb), with HBV quantitative detection value > upper limit\r\n             of normal value; positive for hepatitis C antibody (HCV-Ab), with hepatitis C virus\r\n             RNA quantification > upper limit of normal value.\r\n\r\n         19. History of active tuberculosis.\r\n\r\n         20. Pregnant or breastfeeding women.\r\n\r\n         21. Known suffered from other malignant tumors that have progressed or require treatment\r\n             within 5 years prior to screening (except for well-treated basal cell carcinoma of the\r\n             skin, squamous cell carcinoma of the skin, superficial bladder cancer or cured\r\n             carcinoma in situ, such as breast carcinoma in situ, etc.).\r\n\r\n         22. Other circumstances that may increase the risk associated with the study medication,\r\n             or interfere with the interpretation of the study results, or affect the compliance of\r\n             the study, etc. may not be suitable for participation in the study as determined by\r\n             the investigator.\r\n\r\n         23. Previous use of doxorubicin liposomes.\r\n\r\n         24. Previous use of other anthracycline/anthraquinone drugs (including non-doxorubicin\r\n             liposomes) with a converted cumulative dose equivalent to doxorubicin 300 mg/m^2, or\r\n             previous use of anthracyclines causing cardiac disease.\r\n      ","sponsor":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd.","sponsor_type":"Industry","conditions":"Epithelial Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SG001","description":"Recombinant Anti-PD-1 Fully Human Monoclonal Antibody Injection, 240 mg q2w"},{"intervention_type":"Drug","name":"Drug: Doxorubicin hydrochloride liposome injection","description":"Doxorubicin hydrochloride liposome injection 40mg/m ^2 q4w"}],"outcomes":[{"outcome_type":"primary","measure":"1. Objective response rate (ORR, assessed by investigators according to RECIST 1.1 criteria)","time_frame":"From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest.","description":"ORR is defined as the proportion of all patients with a best evaluation of complete response or partial response (according to RECIST version 1.1 criteria), from the date of administration to the date of patients' withdrawal or study completion or termination."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 3 years.","description":"PFS measured from the date of administration to the date of investigator firstly assessed disease progression (according to RECIST version 1.1 criteria) or death from any cause (in the absence of progression)."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 2 years.","description":"DCR is defined as the proportion of all patients with best a evaluation of complete response or partial response or stable disease (according to RECIST version 1.1 criteria) from the date of administration to the date of patients' withdrawal or study completion or termination."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 3years..","description":"OS measured from the date of administration to the date of death from any cause."},{"outcome_type":"secondary","measure":"Treatment emergent adverse event (TEAEs)","time_frame":"From the date of signing Informed Consent Form (ICF) up to 28 days following the last dose of study drug, immune related adverse events will be recorded until 90 days after the last dose.","description":"Amount, severity, and duration of TEAEs will be evaluated according to NCI-CTCAE V5.0."}]}
{"nct_id":"NCT04972097","start_date":"2021-09-30","phase":"N/A","enrollment":118,"brief_title":"Pivotal Study of the NanoKnife System for the Ablation of Prostate Tissue","official_title":"Pivotal Study of the NanoKnife System for the Ablation of Prostate Tissue in an Intermediate-Risk Patient Population","primary_completion_date":"2023-09-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-09-30","last_update":"2021-09-10","description":"Pivotal study to evaluate the use of the NanoKnife System as a focal therapy option for prostate cancer patients. This study will assess the safety and effectiveness of the device when used to ablate prostate tissue in intermediate-risk prostate cancer patients.","other_id":"2021-ONC-01","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":50,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Is greater than 50 years of age\r\n\r\n          2. Has at least a 10-year life expectancy\r\n\r\n          3. Has histologically confirmed organ-confined prostate cancer, clinical stage  T2c\r\n\r\n          4. Has a PSA  15 ng/mL or PSA density < 0.2 ng/mL2 if PSA is > 15 ng/mL\r\n\r\n          5. Has Gleason score 3+4 or 4+3\r\n\r\n          6. Has no evidence of extraprostatic extension by mpMRI\r\n\r\n          7. Has no evidence of seminal vesicle invasion by mpMRI, and if suspected, confirmed by\r\n             biopsy\r\n\r\n          8. Physician is able to visualize prostate gland adequately on transrectal ultrasound\r\n             imaging during enrollment evaluation\r\n\r\n          9. Transperineal or transrectal targeted prostate biopsies of lesion, plus 10 core\r\n             systematic biopsies to include adequate sampling of the peripheral zone correlating\r\n             with an intermediate risk lesion in the area of the MR-visible lesion\r\n\r\n         10. A visible lesion on mpMRI that is accessible to Irreversible Electroporation (IRE)\r\n             treatment (Note: A non-MRI visible lesion detected via systematic standard biopsy will\r\n             not be considered an exclusion criterion provided the non-MRI visible lesion is\r\n             singularly located in the contralateral hemisphere of the prostate; is Gleason 6; and\r\n             comprises no more than 6 mm linear extent of prostate-bearing tissue in a single core\r\n             on standard biopsy)\r\n\r\n         11. Has signed a written informed consent and in the judgment of the physician, the study\r\n             is in the best interest of the subject\r\n\r\n         12. Understands and accepts the obligation and is logistically able to present for all\r\n             scheduled follow-up visits\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has known hypersensitivity to pancuronium bromide, atricurium or cisatricurium\r\n\r\n          2. Is unfit for anesthesia or has a contraindication for agents listed for paralysis\r\n\r\n          3. Has an active urinary tract infection (UTI)\r\n\r\n          4. Has a history of bladder neck contracture\r\n\r\n          5. Is interested in future fertility\r\n\r\n          6. Has a history (within 3 years) of inflammatory bowel disease\r\n\r\n          7. Has a concurrent major debilitating illness\r\n\r\n          8. Had active treatment for a malignancy within 3 years, including malignant melanoma,\r\n             except for prostate cancer or other types of skin cancer\r\n\r\n          9. Has any active implanted electronic device (e.g., pacemaker)\r\n\r\n         10. Is unable to catheterize due to a urethral stricture disease\r\n\r\n         11. Has had prior or current prostate cancer therapies:\r\n\r\n               1. Biologic therapy for prostate cancer\r\n\r\n               2. Chemotherapy for prostate cancer\r\n\r\n               3. Hormonal therapy for prostate cancer within three months of procedure\r\n\r\n               4. Radiotherapy for prostate cancer\r\n\r\n               5. Surgery for prostate cancer\r\n\r\n         12. Has had prior transurethral prostatectomy (TURP), stricture surgery, urethral stent or\r\n             prostatic implants\r\n\r\n         13. Has had prior major rectal surgery (except hemorrhoids)\r\n\r\n         14. Is unfit for pelvic MRI scanning (e.g., severe claustrophobia, permanent cardiac\r\n             pacemaker, metallic implants that are likely to contribute significant image\r\n             artifacts, allergy or contraindication to gadolinium (to enhance MRI))\r\n\r\n         15. Is actively bleeding, is anticoagulated or on blood thinning medications, or has a\r\n             bleeding disorder\r\n\r\n         16. Is a member of a vulnerable population such as prisoners, handicapped or mentally\r\n             disabled persons, or economically or educationally disadvantaged persons\r\n\r\n         17. In the opinion of the treating physician, has a contraindication listed in the current\r\n             NanoKnife System User Manual (section 2.3)\r\n      ","sponsor":"Angiodynamics, Inc.","sponsor_type":"Industry","conditions":"Prostate Cancer","interventions":[{"intervention_type":"Device","name":"Device: Irreversible Electroporation","description":"IRE of the prostate is typically performed with the subject in the lithotomy position, with 2-6 monopolar probes placed through the perineum using a brachytherapy grid and ultrasound or CT guidance. IRE supplies the targeted tissue with high voltage (2-3 kV) direct current pulses lasting up to 100 microseconds through the electrode probes."}],"outcomes":[{"outcome_type":"primary","measure":"Rate of negative in-field biopsy at 12 months","time_frame":"12 months","description":"To determine the NanoKnife System's ablation effectiveness by measuring the negative in-field biopsy rate at 12 months"},{"outcome_type":"primary","measure":"Incidence of adverse events by type and CTCAE v5.0 severity through 12 months","time_frame":"12 months","description":"To determine the NanoKnife System's procedural and post-procedural safety profile by evaluation adverse event incidence, type, and severity through 12 months"},{"outcome_type":"secondary","measure":"Rate of negative in-field biopsy at 12 months as defined by the Delphi consensus criterion","time_frame":"12 months","description":"Rate of negative in-field biopsy at 12 months as defined by the Delphi consensus criterion of absence of clinically significant disease (≤ 3 mm of Gleason ≤ 6 disease in any biopsy core is insignificant)"},{"outcome_type":"secondary","measure":"Assessment of urinary function by comparison of pre- and post-operative UCLA Expanded Prostate Cancer Index Composite","time_frame":"12 months","description":"Assessment of urinary function by comparison of pre- and post-operative UCLA Expanded Prostate Cancer Index Composite (UCLA-EPIC) Urinary Domain and International Prostate Symptom Scores (IPSS) and IPSS Quality of Life2 (IPSS-QoL) scores."},{"outcome_type":"secondary","measure":"Assessment of erectile function by comparison of pre- and post-operative IIEF-15 potency scores","time_frame":"12 months","description":"Assessment of erectile function by comparison of pre- and post-operative 15-Item International Index of Erectile Function (IIEF-15) potency scores."},{"outcome_type":"secondary","measure":"Effectiveness of therapy by measurement of prostate-specific antigen (PSA) kinetics","time_frame":"12 months","description":"Effectiveness of therapy by measurement of prostate-specific antigen (PSA) kinetics including time to PSA nadir."},{"outcome_type":"secondary","measure":"Assessment of changes in prostate volume","time_frame":"12 months","description":"Assessment of changes in prostate volume by comparison of pre-treatment and 12-month prostate volume measured via mpMRI."},{"outcome_type":"secondary","measure":"Assessment of ablation effectiveness by evaluation of prostate tissue by mpMRI","time_frame":"12 months","description":"Assessment of ablation effectiveness by evaluation of prostate tissue by mpMRI at 3 to 10 days post-treatment and at 12 months post-treatment."},{"outcome_type":"secondary","measure":"Assessment of need for secondary or adjuvant treatment","time_frame":"12 months","description":"Assessment of need for secondary or adjuvant treatment following treatment with the NanoKnife System."},{"outcome_type":"secondary","measure":"Evaluation of subject reported pre- and post-operative Quality of Life","time_frame":"12 months","description":"Evaluation of subject reported pre- and post-operative Quality of Life (QoL) using the 5-dimension scale EuroQol (EQ-5D®)."}]}
{"nct_id":"NCT04958785","start_date":"2021-09-30","phase":"Phase 2","enrollment":110,"brief_title":"Study to Evaluate the Safety and Efficacy of Magrolimab in Combination With Nab-Paclitaxel or Paclitaxel Versus Nab-Paclitaxel or Paclitaxel in Previously Untreated Adults With Metastatic Triple-Negative Breast Cancer","official_title":"A Phase 2, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Nab-Paclitaxel or Paclitaxel Versus Nab-Paclitaxel or Paclitaxel in Previously Untreated Patients With Metastatic Triple-Negative Breast Cancer","primary_completion_date":"2024-06-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-06-30","last_update":"2021-08-24","description":"The primary objective of this study for the Safety Run-In Cohort is to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with nab-paclitaxel or paclitaxel in metastatic triple-negative breast cancer (mTNBC). The primary objective of this study for the Randomized Cohorts is to evaluate the efficacy of magrolimab in combination with nab-paclitaxel or paclitaxel in solid tumors as determined by progression-free survival (PFS) by investigator assessment.","other_id":"GS-US-586-6144","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Individual has provided informed consent\r\n\r\n          -  Individual is willing and able to comply with clinic visits and procedures outlined in\r\n             the study protocol\r\n\r\n          -  Individuals must have an Eastern Cooperative Oncology Group (ECOG) performance status\r\n             of 0 or 1\r\n\r\n          -  Laboratory measurements, blood counts: Adequate hemoglobin, neutrophil, and platelet\r\n             counts\r\n\r\n          -  Laboratory measurements, renal function: Adequate creatinine and liver function tests\r\n\r\n          -  Male and female individuals of childbearing potential who engage in heterosexual\r\n             intercourse must agree to use protocol-specified method(s) of contraception\r\n\r\n          -  Measurable disease according to RECIST, version 1.1. Previously irradiated lesions can\r\n             be considered as measurable disease only if disease progression has been unequivocally\r\n             documented at that site since radiation\r\n\r\n          -  Individuals must be willing to provide baseline tumor tissue from a core or excisional\r\n             biopsy (fine needle aspirate is not adequate). A newly obtained biopsy (within 90 days\r\n             prior to study treatment start) is strongly preferred, but an archival sample (within\r\n             6 months prior to study treatment start) is acceptable. Individuals will also be\r\n             requested to consent to a mandatory on-treatment tumor biopsy unless not feasible as\r\n             determined by the investigator and discussed with the sponsor\r\n\r\n          -  Individuals previously untreated for unresectable locally advanced or mTNBC that is\r\n             histologically or cytologically confirmed based on the most recent analyzed biopsy or\r\n             other pathology specimen, as defined by the most recent American Society of Clinical\r\n             Oncology/College of American Pathologists (ASCO/CAP) guideline\r\n\r\n          -  Individuals whose tumors do not express programmed cell death ligand 1 (PD-L1), as\r\n             determined by an approved test according to local regulations\r\n\r\n          -  Prior systemic treatment for neoadjuvant and/or adjuvant therapy and/or curative\r\n             intent radiation therapy is permitted if completed at least 6 months prior to\r\n             enrollment.\r\n\r\n        Note: Maintenance therapies are not counted as separate lines of therapy.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Positive serum pregnancy test\r\n\r\n          -  Breastfeeding female\r\n\r\n          -  Active central nervous system (CNS) disease. Individuals with asymptomatic and stable,\r\n             treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who\r\n             have not received corticosteroids for at least 4 weeks) are allowed\r\n\r\n          -  Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of\r\n             packed RBC transfusions during the 4-week period prior to screening. RBC transfusions\r\n             are permitted during the screening period and prior to enrollment to meet the\r\n             hemoglobin inclusion criteria\r\n\r\n          -  History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the\r\n             last 3 months\r\n\r\n          -  Known hypersensitivity to any of the study drugs, the metabolites, or formulation\r\n             excipient\r\n\r\n          -  Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein\r\n             alpha-targeting agents\r\n\r\n          -  Current participation in another interventional clinical trial\r\n\r\n          -  Known inherited or acquired bleeding disorders\r\n\r\n          -  Significant disease or medical conditions, as assessed by the investigator and\r\n             sponsor, that would substantially increase the risk-benefit ratio of participating in\r\n             the study\r\n\r\n          -  Known active or chronic hepatitis B or C infection or human immunodeficiency virus\r\n             infection in medical history)\r\n\r\n          -  Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or\r\n             investigational agents within 4 weeks prior to magrolimab is not permitted.\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"Gilead Sciences","sponsor_type":"Industry","conditions":"Triple-Negative Breast Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Magrolimab","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Nab-Paclitaxel","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Administered intravenously"}],"outcomes":[{"outcome_type":"primary","measure":"Safety Run-in Cohort: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0","time_frame":"First dose date up to 35 months"},{"outcome_type":"primary","measure":"Randomized Cohort: Progression Free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1","time_frame":"Up to 35 months","description":"PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment and Independent Central Review","time_frame":"Up to 35 months","description":"ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), as measured by RECIST version 1.1, as determined by investigator assessment and independent central review."},{"outcome_type":"secondary","measure":"Randomized Cohort: PFS as Determined by Independent Central Review Using RECIST Version 1.1","time_frame":"Up to 35 months","description":"PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by independent central review per RECIST version 1.1, or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Randomized Cohort: Duration of Response (DOR) as Determined by Investigator Assessment per RECIST Version 1.1","time_frame":"Up to 35 months","description":"DOR is defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Randomized Cohort: Duration of Response (DOR) as Determined by Independent Central Review per RECIST Version 1.1","time_frame":"Up to 35 months","description":"DOR is defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, as determined by independent central review per RECIST version 1.1, or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Randomized Cohort: Overall Survival (OS)","time_frame":"Up to 35 months","description":"OS is defined as time from date of randomization to death from any cause."},{"outcome_type":"secondary","measure":"Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time","time_frame":"Up to end of treatment (approximately 35 months)"},{"outcome_type":"secondary","measure":"Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab","time_frame":"Up to end of treatment (approximately 35 months)"}]}
{"nct_id":"NCT04939701","start_date":"2021-09-30","phase":"Phase 1/Phase 2","enrollment":339,"brief_title":"Study of ASP0739 Alone and With Pembrolizumab in Advanced Solid Tumors With NY-ESO-1 Expression Participants","official_title":"A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP0739 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Known to Express NY-ESO-1","primary_completion_date":"2026-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2028-01-31","last_update":"2021-08-30","description":"The purpose of this study is to evaluate the safety, and tolerability of ASP0739, when administered as a single agent and in combination with pembrolizumab. This study will also evaluate the clinical response and other measures of anticancer activity of ASP0739 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.","other_id":"0739-CL-0101","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Phase 1 Dose Escalation only:\r\n\r\n        - Participant has relapsed/refractory (R/R) solid tumor known to express NY-ESO-1 after\r\n        completing available Standard of Care (SOC) therapy or is not a candidate for SOC therapy.\r\n        NY-ESO-1 expression status is not required for participant entry.\r\n\r\n        Phase 2 Single agent and Combination Therapy only:\r\n\r\n          -  Participant has relapsed/refractory (R/R) synovial sarcoma (SS) or myxoid/round cell\r\n             liposarcoma (MRCL) disease after undergoing available SOC treatment or is not a\r\n             candidate for SOC therapy (must have previously received either an anthracycline or\r\n             ifosfamide containing regimen or another systemic regimen, if not a candidate for\r\n             either agent).\r\n\r\n               -  Participant has not received prior checkpoint inhibitor therapy (i.e., Programmed\r\n                  Cell Death Protein 1 [PD-1]/Programmed Death Ligand 1 [PD-L1] treatment naive)\r\n\r\n               -  SS: confirmation by the presence of a translocation between SYT on the X\r\n                  chromosome and SSX1, SSX2, or SSX4 on chromosome 18 (may be presented in the\r\n                  pathology report as t [X;18]).\r\n\r\n               -  MRCL: confirmation by the presence of the reciprocal chromosomal translocation t\r\n                  (12;16) (q13;p11) or t(12;22)(q13;q12).\r\n\r\n          -  Participant has R/R ovarian cancer that is:\r\n\r\n               -  platinum resistant OR platinum-sensitive, but the participant is not a candidate\r\n                  for platinum or other SOC therapy.\r\n\r\n               -  Participant has not received prior checkpoint inhibitor therapy (i.e., naive\r\n                  PD-1/PD-L1 treatment participants).\r\n\r\n          -  Participant has R/R solid tumor (melanoma, non-small cell lung cancer\r\n             [NSCLC]-adenocarcinoma and squamous cell, or esophageal squamous cell carcinoma\r\n             [ESCC]) after available SOC treatment or is not a candidate for SOC therapy\r\n             (single-agent only).\r\n\r\n          -  Participant consents to provide an archival tumor specimen in a tissue block or\r\n             unstained serial slides prior to IP administration.\r\n\r\n          -  Participant in phase 2 consents to provide tumor specimen obtained within 56 days\r\n             prior to first dose of study treatment, as tissue block or unstained serial slides.\r\n\r\n          -  Participant in phase 2 consents to undergoing a tumor biopsy (core needle biopsy or\r\n             excision) during the treatment period.\r\n\r\n          -  Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of <=\r\n             2.\r\n\r\n          -  Participant with life expectancy of >= 12 weeks at the time of screening.\r\n\r\n          -  Participant must meet criteria for clinical laboratory tests during screening period.\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant and at least\r\n             one of the following conditions apply:\r\n\r\n               -  Not a woman of childbearing potential (WOCBP) OR\r\n\r\n               -  WOCBP who agrees to follow the contraceptive guidance throughout the treatment\r\n                  period and for at least 6 months after the final investigational product (IP)\r\n                  administration.\r\n\r\n          -  Female participant must not be breastfeeding at screening or during the study period\r\n             and for 6 months after the final IP administration.\r\n\r\n          -  Female participant must not donate ova at screening and throughout the study period\r\n             and for 6 months after the final IP administration.\r\n\r\n          -  A male participant with female partner(s) of childbearing potential must agree to use\r\n             contraception during the treatment period and for at least 6 months after the final IP\r\n             administration.\r\n\r\n          -  Male participant must not donate sperm starting at screening and throughout the study\r\n             period and for 6 months after the final IP administration.\r\n\r\n          -  Participant agrees not to participate in another interventional study while on\r\n             treatment.\r\n\r\n          -  Participant has at least 1 measurable lesion per immune response evaluation criteria\r\n             in solid tumors (iRECIST). The measurable lesion must be outside the field of\r\n             radiation if participant had prior radiotherapy < 3 months from the completion of\r\n             radiation.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participant has persistent non-hematological toxicities of >= grade 2 (National Cancer\r\n             Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0),\r\n             with symptoms and objective findings from treatment (including chemotherapy, kinase\r\n             inhibitors, immunotherapy, experimental agents, radiation or surgery).\r\n\r\n          -  Participant has received any of the following therapies (for inclusion in the study,\r\n             all abnormalities must have returned to <= grade 1):\r\n\r\n               -  Systemic immunomodulators (checkpoint inhibitors)-except the NY-ESO-1 solid tumor\r\n                  (melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC) cohorts, which may\r\n                  have received prior checkpoint inhibitor therapy\r\n\r\n               -  Immunosuppressive drugs including steroids <= 14 days prior to treatment\r\n\r\n               -  Cytotoxic agents <= 14 days prior to treatment\r\n\r\n               -  Investigational agent <= 21 days prior to treatment or 5 half-lives, whichever is\r\n                  shorter\r\n\r\n               -  Radiation therapy <= 21 days prior to treatment\r\n\r\n          -  Participant has clinically active or untreated nervous system metastases. Participants\r\n             with previously treated Central Nervous System (CNS) metastases are eligible, if they\r\n             are clinically stable and have no evidence of CNS progression by imaging for at least\r\n             4 weeks prior to start of study treatment and are not requiring immunosuppressive\r\n             doses of systemic steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of\r\n             prednisone or equivalent) for longer than 2 weeks.\r\n\r\n          -  Participant has an active autoimmune disease. Participant with type 1 diabetes\r\n             mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or\r\n             skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic\r\n             treatment are allowed.\r\n\r\n          -  Participant was discontinued from prior immunomodulatory therapy due to a grade >= 3\r\n             toxicity that was mechanistically related (e.g., immune related) to the agent.\r\n\r\n          -  Participant has known history of serious hypersensitivity reaction to a known\r\n             ingredient of ASP0739 or pembrolizumab or severe hypersensitivity reaction to\r\n             treatment with another monoclonal antibody.\r\n\r\n          -  Participant has a prior malignancy active (i.e., requiring treatment or intervention)\r\n             within the previous 2 years prior to screening visit, except for locally curable\r\n             malignancies that have been apparently cured, such as basal or squamous cell skin\r\n             cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.\r\n\r\n          -  Participant has received a prior allogeneic bone marrow or solid organ transplant.\r\n\r\n          -  Participant has an active uncontrolled infection within 14 days of treatment.\r\n\r\n          -  Participant is known to have human immunodeficiency virus infection.\r\n\r\n          -  Participant has active hepatitis B or C or other active hepatic disorder or\r\n             participant is on hepatitis treatment. Hepatitis C RNA testing is not required in\r\n             participants with negative hepatitis C antibody testing.\r\n\r\n          -  Participant has any condition which makes the participant unsuitable for study\r\n             participation.\r\n\r\n          -  Participant has had a major surgical procedure and has not completely recovered within\r\n             28 days prior to the start of study treatment.\r\n\r\n          -  Participant has had a myocardial infarction or unstable angina within 6 months prior\r\n             to the start of study treatment or currently has an uncontrolled illness including,\r\n             but not limited to, symptomatic congestive heart failure, clinically significant\r\n             cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric\r\n             illness/social situations that would limit compliance with study requirements.\r\n\r\n          -  Participant is expected to require another form of anti-cancer therapy while on study\r\n             treatment.\r\n\r\n          -  Participants for the combination therapy arm cohorts must not have known\r\n             microsatellite instability or deficient MisMatch Repair.\r\n\r\n        Additional Exclusion Criteria for Participants in Combination Therapy Cohorts\r\n\r\n          -  Participants with a history of myocarditis or congestive heart failure (as defined by\r\n             New York Heart Associated Functional Classification III or IV), as well as unstable\r\n             angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial\r\n             infarction 6 months prior to study entry.\r\n\r\n          -  Participants with active interstitial lung disease (ILD)/pneumonitis or a history of\r\n             ILD/pneumonitis requiring treatment with systemic steroids.\r\n\r\n          -  Participants with baseline pulse oximetry < 92% \"on Room air.\"\r\n      ","sponsor":"Astellas Pharma Global Development, Inc.","sponsor_type":"Industry","conditions":"Ovarian Cancer|NSCLC|ESCC|Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: ASP0739","description":"Intravenous (IV)"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Intravenous (IV)"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 Single Agent","time_frame":"28 days","description":"A DLT is defined as any of the following occurring within 28 days of the first dose on cycle 1 day 1 (C1D1) considered related to IP.\r\nGrade (Gr) ≥ 2 autoimmune reaction; Gr 3 immune-related adverse events (irAEs) not resolving to Gr ≤ 1 in 3-5 days; Gr 4 irAEs; Gr ≥ 3 non-hematological AEs not resolving to Gr ≤ 2 within 72 hours of onset; Gr 4 neutropenia; Gr 3 febrile neutropenia; Gr 4 thrombocytopenia; Gr 3 anemia/thrombocytopenia with transfusion; Gr 4 anemia; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) (Gr ≥ 3) without liver metastases; AST/ALT > 8 x ULN with liver metastases; Confirmed Hy's Law; Gr ≥ 3 liver function test (LFT) abnormality lasting ≥ 7 days; Gr 5 treatment-related toxicity; > 2 week delay in cycle 2 due to treatment-related toxicity."},{"outcome_type":"primary","measure":"Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 + Pembrolizumab Safety Lead-in","time_frame":"28 days","description":"A DLT is defined as any of the following occurring within 28 days of the first dose on C1D1 considered related to IP.\r\nGr ≥ 2 autoimmune reaction; Gr 3 irAEs not resolving to Gr ≤ 1 in 3-5 days; Gr 4 irAEs; Gr ≥ 3 non-hematological AEs not resolving to Gr ≤ 2 within 72 hours of onset; Gr 4 neutropenia; Gr 3 febrile neutropenia; Gr 4 thrombocytopenia; Gr 3 anemia/thrombocytopenia with transfusion; Gr 3 thrombocytopenia with hospitalization; Gr 4 anemia; AST/ALT > 5 x ULN (Gr ≥ 3) without liver metastases; AST/ALT > 8 x ULN with liver metastases; Confirmed Hy's Law; Total Bilirubin > 3 x ULN (Gr ≥ 3); Gr ≥ 3 LFT abnormality at least possibly related to study drug lasting ≥ 7 days; Gr 5 treatment-related toxicity; > 2 week delay in cycle 2 due to treatment-related toxicity; Gr ≥ 2 pneumonitis; Gr ≥ 2 encephalopathy, meningitis, motor/sensory neuropathy; Guillain-Barre syndrome/myasthenic syndrome/myasthenia gravis; Infusion-related reaction requiring infusion discontinuation."},{"outcome_type":"primary","measure":"Number of Participants with adverse events (AEs)","time_frame":"Up to 27 months","description":"An AE is any untoward medical occurrence in a participant temporally associated with the use of study IP and other study treatments, whether or not considered related to the study IP, and other study treatments. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study IP and other study treatments. This includes events related to the comparator and events related to the (study) procedures. AEs will be graded using NCI-CTCAE version 5.0."},{"outcome_type":"primary","measure":"Number of Participants with Serious Adverse Events (SAEs)","time_frame":"Up to 27 months","description":"An AE is considered \"serious\" if the event results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; other medically important events."},{"outcome_type":"primary","measure":"Number of participants with laboratory value abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant laboratory values."},{"outcome_type":"primary","measure":"Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant 12-lead ECG values."},{"outcome_type":"primary","measure":"Number of participants with vital sign abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant vital sign values."},{"outcome_type":"primary","measure":"Number of participants with physical exam abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant physical exam values."},{"outcome_type":"primary","measure":"Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status","time_frame":"Up to 27 months","description":"The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance."},{"outcome_type":"primary","measure":"Objective Response Rate per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review","time_frame":"Up to 36 months","description":"iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed Complete Response (iCR) or Partial Response (iPR) per iRECIST by Independent Central Review."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1","time_frame":"Up to 36 months","description":"ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per RECIST v1.1."},{"outcome_type":"secondary","measure":"Disease Control Rate per iRECIST (iDCR)","time_frame":"Up to 36 months","description":"iDCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR, iPR or stable disease (SD), per iRECIST."},{"outcome_type":"secondary","measure":"Disease Control Rate per RECIST v1.1 (DCR)","time_frame":"Up to 36 months","description":"DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or stable disease (SD), per RECIST v1.1."},{"outcome_type":"secondary","measure":"Progression-Free Survival per iRECIST (iPFS) by Independent Central Review","time_frame":"Up to 36 months","description":"iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST, whichever comes first, as assessed by Independent Central Review."},{"outcome_type":"secondary","measure":"iPFS per iRECIST by local assessment","time_frame":"Up to 36 months","description":"iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST, whichever comes first, as assessed by local assessment."},{"outcome_type":"secondary","measure":"Progression-Free Survival per RECIST v1.1 (PFS) by Independent Central Review","time_frame":"Up to 36 months","description":"PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1, whichever comes first, as assessed by independent central review."},{"outcome_type":"secondary","measure":"PFS per RECIST v1.1 by local assessment","time_frame":"Up to 36 months","description":"PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1, whichever comes first, as assessed by local assessment."},{"outcome_type":"secondary","measure":"Duration of Overall Survival (OS)","time_frame":"Up to 48 months","description":"OS is defined as the time from the date of first dose until the date of death from any cause."},{"outcome_type":"secondary","measure":"Duration of Response per iRECIST (iDOR) by Independent Central Review","time_frame":"Up to 36 months","description":"iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST, as assessed by Independent Central Review."},{"outcome_type":"secondary","measure":"iDOR per iRECIST by local assessment","time_frame":"Up to 36 months","description":"iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST, as assessed by local assessment."},{"outcome_type":"secondary","measure":"Duration of Response per RECIST (DOR) v1.1 by Independent Central Review","time_frame":"Up to 36 months","description":"DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1, as assessed by Independent Central Review."},{"outcome_type":"secondary","measure":"DOR per RECIST v1.1 by local assessment","time_frame":"Up to 36 months","description":"DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1, as assessed by local assessment."},{"outcome_type":"secondary","measure":"ORR per iRECIST (iORR) by local assessment","time_frame":"Up to 36 months","description":"iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR or iPR, by local assessment."}]}
{"nct_id":"NCT04914897","start_date":"2021-09-30","phase":"Phase 2","enrollment":354,"brief_title":"A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma","official_title":"A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Pleural Mesothelioma","primary_completion_date":"2024-10-21","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-30","last_update":"2021-09-05","description":"Primary Objective: To determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary Objectives: - To confirm the dose and to assess the safety profile of SAR444245 when combined with other anticancer therapies. - To assess other indicators of antitumor activity. - To assess the pharmacokinetic (PK) profile of SAR444245 when given in combination with pembrolizumab. - To assess the immunogenicity of SAR444245.","other_id":"ACT16849","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participant must be 18 years of age (or country's legal age of majority if >18\r\n             years), at the time of signing the informed consent.\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (cohorts A1, A2,\r\n             B1, B2), Stage IV non-squamous NSCLC (cohort A3), or unresectable malignant pleural\r\n             mesothelioma (cohort C1).\r\n\r\n          -  Cohort A1: PD-L1 expression TPS > 50%\r\n\r\n          -  Cohort A2: PD-L1 expression TPS 1 - 49%\r\n\r\n          -  Prior anticancer therapy\r\n\r\n          -  Cohorts A1, A2, A3: No prior systemic therapy for advanced/metastatic NSCLC.\r\n             Participants who received adjuvant or neoadjuvant therapy are eligible if the\r\n             adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development\r\n             of metastatic disease.\r\n\r\n          -  Cohorts B1, B2: One prior anti-PD1/PD-L1 regimen (may include chemotherapy) plus one\r\n             additional chemotherapy regimen\r\n\r\n          -  Cohort C1: One or two prior systemic treatments that include pemetrexed-based regimen\r\n             in combination with platinum agent.\r\n\r\n          -  All cohorts must have a measurable disease\r\n\r\n          -  Mandatory baseline biopsy for the first 20 participants to enroll in cohorts A1, A2\r\n\r\n          -  Cohorts B1 and B2: Based on the Investigator's judgment, either docetaxel or\r\n             pemetrexed is not the best treatment option for the participant.\r\n\r\n          -  Females are eligible to participate if they are not pregnant or breastfeeding, not a\r\n             woman of childbearing potential (WOCBP) or are a WOCBP that agrees:\r\n\r\n        to use approved contraception method and submit to regular pregnancy testing prior to\r\n        treatment and for 180 days after discontinuing study treatment to refrain from donating or\r\n        cryopreserving eggs for 180 days after discontinuing study treatment.\r\n\r\n          -  Males are eligible to participate if they agree to refrain from donating or\r\n             cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved\r\n             contraception during study treatment and for at least 210 days after discontinuing\r\n             study treatment.\r\n\r\n          -  Capable of giving signed informed consent.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2.\r\n\r\n          -  Poor bone marrow reserve\r\n\r\n          -  Poor organ function\r\n\r\n          -  Participants with baseline SpO2 92%.\r\n\r\n          -  Active brain metastases or leptomeningeal disease.\r\n\r\n          -  History of allogenic or solid organ transplant\r\n\r\n          -  Last administration of prior antitumor therapy or any investigational treatment within\r\n             28 days or less than 5 times the half-life, whichever is shorter; major surgery or\r\n             local intervention within 28 days.\r\n\r\n          -  Has received prior IL-2-based anticancer treatment.\r\n\r\n          -  Comorbidity requiring corticosteroid therapy\r\n\r\n          -  Antibiotic use (excluding topical antibiotics) 14 days prior to first dose of IMP\r\n\r\n          -  Severe or unstable cardiac condition within 6 months prior to starting study treatment\r\n\r\n          -  Active, known, or suspected autoimmune disease that has required systemic treatment in\r\n             the past 2 years\r\n\r\n          -  Known second malignancy either progressing or requiring active treatment within the\r\n             last 3 years\r\n\r\n          -  Cohorts A1, A2, A3, C1: Prior treatment with an agent (approved or investigational)\r\n             that blocks the PD1/PD-L1 pathway (participants who joined a study with an\r\n             anti-PD1/PD-L1 but have written confirmation they were on control arm are allowed).\r\n\r\n          -  Receipt of a live-virus vaccination within 28 days of planned treatment start.\r\n             Seasonal flu vaccines that do not contain live virus are permitted.\r\n\r\n        The above information is not intended to contain all considerations relevant to a patient's\r\n        potential participation in a clinical trial.\r\n      ","sponsor":"Sanofi","sponsor_type":"Industry","conditions":"Pleural Mesothelioma|Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SAR444245","description":"Pharmaceutical Form: Solution for infusion Route of Administration: intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Pharmaceutical Form: Solution for infusion Route of Administration: intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Pharmaceutical Form: Solution for infusion Route of Administration: intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Pharmaceutical Form: Solution for infusion Route of Administration: intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Nab-paclitaxel","description":"Pharmaceutical Form: powder for solution for infusion Route of Administration: intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Pharmaceutical Form: powder for solution for infusion Route of Administration: intravenous infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate (ORR)","time_frame":"Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximatively 9 months after the last participant receive first dose.","description":"Objective response rate (ORR), defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), derived based on Investigator's assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Cohort A1, Cohort A2, Cohort A3, Cohort B1 and Cohort B2; per modified RECIST (mRECIST) for Cohort C1."},{"outcome_type":"secondary","measure":"To confirm the dose","time_frame":"Observation period is 1 cycle (21 days)","description":"Incidence of Dose-limiting toxicities (DLTs) during DLT observation period"},{"outcome_type":"secondary","measure":"Assessment of SAR444245 safety profile when combined with other anticancer therapies-Treatment Emergent Adverse Events","time_frame":"From 1st IMP dose up to 30 days after the last dose of IMP","description":"Incidence of Treatment Emergent Adverse Events (TEAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings"},{"outcome_type":"secondary","measure":"Assessment of SAR444245 safety profile when combined with other anticancer therapies-Serious Adverse Events","time_frame":"From 1st IMP dose up to 90 days after the last dose of IMP","description":"Incidence of Serious Adverse Events (SAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings"},{"outcome_type":"secondary","measure":"Time to response","time_frame":"From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months","description":"Time to response defined as the time from the first administration of IMP to the first documented evidence of PR (partial response) or CR (complete response) per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma)."},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months","description":"Duration of response (DoR), defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma) or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Clinical benefit rate","time_frame":"From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months","description":"Clinical benefit rate (CBR) including CR or PR at any time plus stable disease (SD) of at least 6 months (per RECIST 1.1 [for NSCLC] or mRECIST [for mesothelioma])."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months","description":"Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression as per RECIST 1.1 for NSCLC) or mRECIST (for mesothelioma) or death due to any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"To assess the plasma concentrations of SAR444245","time_frame":"At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months."},{"outcome_type":"secondary","measure":"To assess the incidence of anti-drug antibodies (ADAs) against SAR444245.","time_frame":"At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum is up to approximately 24 months."}]}
{"nct_id":"NCT04895748","start_date":"2021-09-30","phase":"Phase 1","enrollment":180,"brief_title":"DFF332 as a Single Agent and in Combination With Everolimus & Immuno-Oncology Agents in Advanced/Relapsed Renal Cancer & Other Malignancies","official_title":"A Phase I/Ib, Open-label, Multi-center Study of DFF332 as a Single Agent and in Combination With Everolimus or IO Agents in Patients With Advanced/Relapsed ccRCC and Other Malignancies With HIF2 Stabilizing Mutations","primary_completion_date":"2025-02-24","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-02-24","last_update":"2021-09-13","description":"This is first in human study of DFF332, a small molecule that targets a protein called HIF2. By acting on HIF2, DFF332 may be able to stop the growth of certain types of cancer. DFF332 will be tested at different doses as single agent and in combination with Everolimus (RAD001, an mTOR inhibitor), and also in combination with Spartalizumab (PDR001, an anti-PD1) plus Taminadenant (NIR178, an adenosine A2A receptor antagonist), in patients with advanced clear cell renal cell carcinoma and other malignancies with HIF stabilizing mutations.","other_id":"CDFF332A12101","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":12,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Male and female  18 years of age For Arm 1B: Male and female of age  12 years of age\r\n\r\n          2. Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC).\r\n             Disease must be measurable as determined by RECIST v1.1.\r\n\r\n             For Arm 1B: histologically confirmed and documented malignancies in the context of the\r\n             following cancer predisposing syndromes/disorders or harboring somatic mutations on\r\n             one of these genes:\r\n\r\n               -  Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)\r\n\r\n               -  Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell\r\n                  carcinoma)\r\n\r\n               -  Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary\r\n                  paraganglioma and pheochromocytoma syndrome)\r\n\r\n               -  Malignancies with EPAS1/HIF2A mutations\r\n\r\n               -  Malignancies with ELOC/TCEB1 mutations Note: Mutations must have been previously\r\n                  identified through local molecular assays.\r\n\r\n          3. Patient with unresectable, locally advanced or metastatic ccRCC with documented\r\n             disease progression following therapy with PD-1/L1 checkpoint inhibitor and a VEGF\r\n             targeted therapy as monotherapy or in combination.\r\n\r\n             Escalation: No restriction on the number of prior treatments Expansion (with the\r\n             exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease\r\n             For Arm 1B: Patients must have either metastatic disease or locally advanced disease\r\n             that is unresectable or that patients be unfit for resection or other treatment\r\n             modalities. Patients must have received prior standard therapy appropriate for their\r\n             tumor type and stage of disease, and have no available therapies of proven clinical\r\n             benefit; or in the opinion of the investigator, would be unlikely to tolerate or\r\n             derive clinically meaningful benefit from appropriate standard of care therapy.\r\n\r\n          4. For patients age  16 years: ECOG performance status  1 For patients age  12 and <\r\n             16 years: Lansky performance status  70\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. History of seizure disorder & extrapyramidal (EPS) symptoms\r\n\r\n          2. Impaired cardiac function or clinically significant cardiac disease, including any of\r\n             the following:\r\n\r\n               -  Clinically significant and/or uncontrolled heart disease such as congestive heart\r\n                  failure requiring treatment (NYHA Grade  2), uncontrolled hypertension\r\n\r\n               -  Patients with corrected QT using the Fridericia's correction (QTcF) > 470 msec\r\n                  for all patients on screening ECG or congenital long QT syndrome Acute myocardial\r\n                  infarction or unstable angina < 3 months prior to study entry\r\n\r\n               -  History of stroke or transient ischemic event requiring medical therapy\r\n\r\n               -  Concomitant clinically significant cardiac arrhythmias, e.g. sustained\r\n                  ventricular tachycardia, and clinically significant second or third degree AV\r\n                  block without a pacemaker\r\n\r\n          3. Treatment with any of the following anti-cancer therapies prior to the first dose of\r\n             study treatment within the stated timeframes:\r\n\r\n               1.  4 weeks for radiation therapy or limited field radiation for palliation within\r\n                   2 weeks prior to the first dose of study treatment.\r\n\r\n               2.  4 weeks or  5 half-lives (whichever is shorter) for chemotherapy or biological\r\n                  therapy (including monoclonal antibodies) or continuous or intermittent small\r\n                  molecule therapeutics or any other investigational agent.\r\n\r\n               3.  6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea\r\n                  and mitomycin C.\r\n\r\n               4.  4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1\r\n                  antagonists.\r\n\r\n               5. Patients who have undergone major surgery  4 weeks prior to first dose of study\r\n                  treatment or who have not recovered for the surgical procedure.\r\n\r\n          4. Patient previously treated with a HIF2 inhibitor.\r\n\r\n          5. Uncontrolled concurrent illness including, but not limited to, ongoing active\r\n             infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active\r\n             bleeding diatheses, including any Patient known to have evidence of acute or chronic\r\n             hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric\r\n             illness/social situation that in the investigator's opinion would limit compliance\r\n             with study requirements or compromise the ability of the patient to give written\r\n             informed consent. Patients with chronic HBV or HCV disease that is controlled under\r\n             antiviral therapy are allowed in the expansion parts but not in the escalation parts.\r\n\r\n          6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of\r\n             study treatment.\r\n\r\n          7. Presence of Grade  2 toxicity according to National Cancer Institute (NCI) Common\r\n             Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy with\r\n             the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less\r\n             is permitted), ototoxicity, and alopecia.\r\n\r\n          8. Pregnant or nursing (lactating) women\r\n\r\n        Other protocol-defined inclusion/exclusion criteria may apply.\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Carcinoma, Renal Cell","interventions":[{"intervention_type":"Drug","name":"Drug: DFF332","description":"Hif2alpha inhibitor"},{"intervention_type":"Drug","name":"Drug: RAD001","description":"mTOR inhibitor"},{"intervention_type":"Drug","name":"Drug: PDR001","description":"anti-PD-1"},{"intervention_type":"Drug","name":"Drug: NIR178","description":"Adenosine A2A antagonist receptor"}],"outcomes":[{"outcome_type":"primary","measure":"Number of participants with dose interruptions and dose reductions","time_frame":"3 years","description":"Number of participants with dose interruptions and dose reductions to characterize the tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced ccRCC and advanced malignancies with HIF stabilizing mutations."},{"outcome_type":"primary","measure":"Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)","time_frame":"3 years","description":"Number of participants with AEs/SAEs to characterize the safety and tolerability of DFF332 as a single agent, in combination with Everolimus (RAD001), and in combination with Spartalizumab (PDR001) plus Taminadenant (NIR178) in patients with advanced clear cell Renal Cell Carcinoma (ccRCC) and advanced malignancies with Hypoxia Inducible Factor (HIF) stabilizing mutations"},{"outcome_type":"primary","measure":"Dose intensity for DFF332 for dose escalation and expansion","time_frame":"3 years","description":"Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure"},{"outcome_type":"primary","measure":"Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 days) for DFF332 as a single agent and in combinations","time_frame":"28 days","description":"Number of participants with DLTs"},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR)","time_frame":"3 years","description":"To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Best Overall Response (BOR)","time_frame":"3 years","description":"To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) for Recommended Dose (RD) only","time_frame":"3 years","description":"To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) for Recommended Dose (RD) Only","time_frame":"3 years","description":"To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"3 years","description":"To assess the anti-tumor activity of DFF332 as single agent and combination in patients with advanced ccRCC and with advanced malignancies with HIF stabilizing mutations based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Maximum Concentration (Cmax) of DFF332 single agent and combination","time_frame":"3 years","description":"PK parameters will be based on plasma concentration of DFF332 and Taminadenant, whole blood concentration of Everolimus, serum concentration of Spartalizumab"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve (AUC) of DFF332 single agent and combination","time_frame":"3 years","description":"PK parameters will be based on plasma concentration of DFF332 single agent and in combination."}]}
{"nct_id":"NCT04806945","start_date":"2021-09-30","phase":"Phase 3","enrollment":482,"brief_title":"A Phase III Study to Evaluate Efficacy and Safety of First-Line Treatment With HLX10 + Chemotherapy in Patients With Advanced Cervical Cancer","official_title":"A Randomized, Double-blind, Placebo Controlled Phase III Study to Investigate Efficacy and Safety of First-Line Treatment With HLX10 (Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection) + Chemotherapy (Carboplatin/Cisplatin and Paclitaxel) vs Chemotherapy (Carboplatin/Cisplatin and Paclitaxel)in Patients With Advanced Cervical Cancer","primary_completion_date":"2024-02-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-10-30","last_update":"2021-08-03","description":"The purpose of this study is to assess the efficacy and safety of HLX10(Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection) plus chemotherapy compared to the efficacy and safety of placebo plus chemotherapy in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Chemotherapy regimens include: paclitaxel plus cisplatin and paclitaxel plus carboplatin. The primary study hypotheses are that the combination of HLX10 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the IRRC or, 2) Overall Survival (OS).","other_id":"HLX10-017-CC301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Has persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous\r\n             carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic\r\n             chemotherapy and is not amenable to curative treatment (such as with surgery and/or\r\n             radiation)\r\n\r\n          2. CPS1\r\n\r\n          3. Has measurable disease per RECIST 1.1 as assessed by IRRC\r\n\r\n          4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within\r\n             14 days prior to randomization\r\n\r\n          5. Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis.\r\n\r\n          2. Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 2 years.\r\n\r\n          3. Has a history of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          4. Has an active infection requiring systemic therapy\r\n\r\n          5. Has a known history of human immunodeficiency virus (HIV) infection\r\n\r\n          6. Has received prior therapy with an anti-PD-1, anti-PD-L1 or with an agent directed to\r\n             another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4\r\n      ","sponsor":"Shanghai Henlius Biotech","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: HLX10","description":"IV infusion."},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Placebo to HLX10","description":"IV infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)","time_frame":"up to approximately 1 years","description":"Baseline until disease progression or death, whichever occurs first"},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 2 years","description":"OS is defined as the time from randomization to death due to any cause."}]}
{"nct_id":"NCT04786964","start_date":"2021-09-30","phase":"Phase 3","enrollment":560,"brief_title":"Study of Pemetrexed+Platinum Chemotherapy With or Without Cosibelimab (CK-301) in First Line Metastatic Non-squamous Non-Small Cell Lung Cancer","official_title":"A Randomized, Open-Label, Phase 3 Study of Cosibelimab (CK-301) in Combination With Platinum+Pemetrexed Chemotherapy in Subjects With First-Line Metastatic Non-squamous Non-Small Cell Lung Cancer","primary_completion_date":"2024-05-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-05-31","last_update":"2021-07-27","description":"This is an efficacy and safety study of cosibelimab (CK-301) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned in a 2:1 ratio to receive cosibelimab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin). The primary hypothesis is that cosibelimab in combination with pemetrexed/platinum chemotherapy prolongs Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.","other_id":"CK-301-301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV\r\n             non-squamous NSCLC.\r\n\r\n          -  Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma\r\n             kinase (ALK)-directed therapy is not indicated.\r\n\r\n          -  Has measurable disease.\r\n\r\n          -  Has not received prior systemic treatment for their advanced/metastatic NSCLC.\r\n\r\n          -  Can provide tumor tissue.\r\n\r\n          -  Has a life expectancy of at least 3 months.\r\n\r\n          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)\r\n             Performance Status.\r\n\r\n          -  Has adequate organ function\r\n\r\n          -  If female of childbearing potential, is willing to use adequate contraception for the\r\n             course of the study through 120 days after the last dose of study medication or\r\n             through 180 days after last dose of chemotherapeutic agents.\r\n\r\n          -  If male with a female partner(s) of child-bearing potential, must agree to use\r\n             adequate contraception starting with the first dose of study medication through 180\r\n             days after the last dose of study medication and chemotherapeutic agents.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has predominantly squamous cell histology NSCLC.\r\n\r\n          -  Is currently participating and receiving study therapy or has participated in a study\r\n             of an investigational agent and received study therapy or used an investigational\r\n             device within 4 weeks prior to administration of study medication.\r\n\r\n          -  Before the first dose of study medication: a) Has received prior systemic cytotoxic\r\n             chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy\r\n             (e.g., erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to\r\n             first dose).\r\n\r\n          -  Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the\r\n             first dose of study medication.\r\n\r\n          -  Completed palliative radiotherapy within 7 days of the first dose of study medication.\r\n\r\n          -  Is expected to require any other form of antineoplastic therapy while on study.\r\n\r\n          -  Received a live-virus vaccination within 30 days of planned start of study medication.\r\n\r\n          -  Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal\r\n             obstruction, peritoneal carcinomatosis.\r\n\r\n          -  Known history of prior malignancy except if participant has undergone potentially\r\n             curative therapy with no evidence of that disease recurrence for 5 years since\r\n             initiation of that therapy, except for successful definitive resection of basal cell\r\n             carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the\r\n             skin, in situ cervical cancer, or other in situ cancers.\r\n\r\n          -  Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis.\r\n\r\n          -  Previously had a severe hypersensitivity reaction to treatment with another monoclonal\r\n             antibody (mAb).\r\n\r\n          -  Known sensitivity to any component of cisplatin, carboplatin or pemetrexed.\r\n\r\n          -  Has active autoimmune disease that has required systemic treatment in past 2 years.\r\n\r\n          -  Is on chronic systemic steroids.\r\n\r\n          -  Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs),\r\n             other than an aspirin dose 1.3 g per day, for a 5-day period (8-day period for\r\n             long-acting agents, such as piroxicam).\r\n\r\n          -  Is unable or unwilling to take folic acid or vitamin B12 supplementation.\r\n\r\n          -  Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1\r\n             (PD-L1) or PD-L2 agent or drug specifically targeting T-cell co-stimulation or immune\r\n             checkpoint pathways.\r\n\r\n          -  Has an active infection requiring therapy.\r\n\r\n          -  Has known history of Human Immunodeficiency Virus (HIV).\r\n\r\n          -  Has known active Hepatitis B or C.\r\n\r\n          -  Has known psychiatric or substance abuse disorder that would interfere with\r\n             cooperation with the requirements of the trial.\r\n\r\n          -  Is a known regular user of any illicit drugs or had a recent history (within the last\r\n             year) of substance abuse (including alcohol).\r\n\r\n          -  Has symptomatic ascites or pleural effusion.\r\n\r\n          -  Has active or history of interstitial lung disease or a history of (non infectious)\r\n             pneumonitis that required steroids or current pneumonitis.\r\n\r\n          -  Has had an allogeneic tissue/solid organ transplant.\r\n\r\n          -  Any known uncontrolled or significant cardiovascular disease.\r\n\r\n          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the\r\n             projected duration of the study.\r\n      ","sponsor":"Checkpoint Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Metastatic Non-squamous Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Cosibelimab","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"IV infusion"},{"intervention_type":"Dietary Supplement","name":"Dietary Supplement: Folic acid 350-1000 g","description":"Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed."},{"intervention_type":"Dietary Supplement","name":"Dietary Supplement: Vitamin B12 1000 g","description":"Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration."},{"intervention_type":"Drug","name":"Drug: Dexamethasone 4mg","description":"For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration."}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Approximately 3 years.","description":"Defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS)","time_frame":"Approximately 3 years.","description":"Defined as the time from randomization until disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"Approximately 3 years.","description":"Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"Approximately 3 years.","description":"Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1) or death from any cause, whichever comes first."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced an Adverse Event (AE)","time_frame":"Approximately 3 years.","description":"An AE is defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug."}]}
{"nct_id":"NCT04416633","start_date":"2021-09-30","phase":"Phase 4","enrollment":200,"brief_title":"Study to Access Safety of Durvalumab in Indian Adult Patients With Locally Advanced, NSCLC and Urothelial Cancer","official_title":"A Prospective, Multicenter, Phase-IV Clinical Trial to Assess Safety of Durvalumab in Indian Adult Patients With Locally Advanced, Unresectable Non-small Cell Lung Cancer (NSCLC) and Urothelial Cancer","primary_completion_date":"2023-03-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-03-31","last_update":"2021-07-13","description":"A prospective, multicenter, Phase-IV clinical trial to assess safety of Durvalumab in Indian adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) and urothelial cancer","other_id":"D133HC00003","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":99,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Provision of signed, written and dated informed consent prior to any study specific\r\n             Procedures\r\n\r\n          2. Male or female aged 18 years or older\r\n\r\n          3. As per local prescribing information and in view of positive benefit-risk assessment,\r\n             patient prescribed Durvalumab treatment as per independent clinical judgment of\r\n             treating physician for either\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Concurrent enrolment in another clinical study, unless it is an observational\r\n             (non-interventional) clinical study or the follow-up period of an interventional study\r\n\r\n          2. Current or prior use of immunosuppressive medication within 14 days before the first\r\n             dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or\r\n             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of\r\n             prednisone, or an equivalent corticosteroid. Systemic steroid administration required\r\n             to manage toxicities arising from radiation therapy delivered as part of the\r\n             chemoradiation therapy for locally advanced NSCLC is allowed.\r\n\r\n          3. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody including durvalumab.\r\n\r\n          4. For NSCLC cohort only:\r\n\r\n               1. Mixed small cell and non-small cell lung cancer histology\r\n\r\n               2. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.\r\n\r\n               3. Patients with Grade 2 pneumonitis from prior chemoradiation therapy\r\n\r\n          5. Active or prior documented autoimmune disease within the past 2 years, inflammatory\r\n             bowel disease (eg, Crohn's disease, ulcerative colitis), primary immunodeficiency,\r\n             organ transplant that requires therapeutic immunosuppression, hypersensitivity to\r\n             study drug or any excipient, leptomeningeal carcinomatosis, tuberculosis.\r\n\r\n             NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic\r\n             treatment (within the past 2 years) are not excluded.\r\n\r\n          6. Female patients who are pregnant, breast-feeding or male or female patients of\r\n             reproductive potential who are not employing an effective method of birth control\r\n\r\n          7. Any condition that, in the opinion of the investigator, would interfere with\r\n             evaluation of the study drug or interpretation of patient safety or study results.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Unresectable Non-small Cell Lung Cancer (NSCLC) and Urothelial Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"500-mg/120-mg IV"}],"outcomes":[{"outcome_type":"primary","measure":"To assess the safety of durvalumab among locally advanced unresectable non-small cell lung carcinoma and metastatic urothelial carcinoma","time_frame":"12 Months","description":"Number, frequency and proportion of patients with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) including interstitial lung disease/pneumonitis-like events, and on-study deaths."}]}
{"nct_id":"NCT03905902","start_date":"2021-09-30","phase":"Phase 3","enrollment":678,"brief_title":"DCVAC/OvCa and Standard of Care (SoC) in Relapsed Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma","official_title":"A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of DCVAC/OvCa Added to Standard of Care in Patients With Relapsed Platinum-sensitive Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma","primary_completion_date":"2027-07-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-07-31","last_update":"2020-11-04","description":"Multi-center, phase III trial of DCVAC/OvCa added to standard of care treatments for relapsed ovarian cancer. Patients will receive study treatment until all doses are administered, or other criteria are met.","other_id":"SOV09","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","intervention_model_description":"parallel-group, placebo-controlled","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed high-grade serous or endometrioid carcinoma of the ovary,\r\n             peritoneum or fallopian tube.\r\n\r\n          -  Without disease progression during preceding platinum-based chemotherapy\r\n\r\n          -  Platinum-sensitive patients defined as Platinum-Free Interval of more than 6 months\r\n             between the end of the last cycle of platinum-based chemotherapy and radiologic\r\n             evidence of progression.\r\n\r\n          -  First relapse identified by the criteria above up to 28 days prior to study\r\n             randomization\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1\r\n\r\n          -  Known BRCA (breast cancer susceptibility gene) mutation status before randomization\r\n\r\n          -  Patient is intended to be treated with bevacizumab, best supportive care (BSC) only or\r\n             PARPi\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Tumor-specific: any other histology sub-type that is not high grade serous or\r\n             endometrioid, however a combination of these is allowed\r\n\r\n          -  Disease Treatment history: started or ongoing systemic treatment for current relapse\r\n             of Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer\r\n             before signing informed consent form (ICF), concomitant use of anti-neoplastic anti-\r\n             hormonal therapy\r\n\r\n          -  Intention to treat with intra-peritoneal chemotherapy\r\n      ","sponsor":"Sotio a.s.","sponsor_type":"Industry","conditions":"Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: DCVAC/OvCa","description":"activated autologous dendritic cells"},{"intervention_type":"Biological","name":"Biological: DCVAC/OvCa placebo","description":"placebo for activated autologous cells"}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival(OS)","time_frame":"Assessed from enrolment up to study completion, approximately 6.6 years","description":"Defined as the time from randomization until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS)","time_frame":"Assessed from enrollment to up to 4 years","description":"Defined as the time from randomization to the earlier date of objective progression or death due to any cause in the absence of progression."},{"outcome_type":"secondary","measure":"Objective Response Rate","time_frame":"Assessed from start of treatment to up to 4 years","description":"Assessment of Objective Response Rate per RECIST1.1 until objective progression as defined by the Investigator."},{"outcome_type":"secondary","measure":"Time to Relapse","time_frame":"Assessed from start of treatment up to 4 years","description":"Assessment of Time to Relapse, per objective progression according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of Response","time_frame":"Assessed from start of study treatment up to 4 years","description":"Assessment of Duration of Response until objective progression per RECIST 1.1."},{"outcome_type":"secondary","measure":"Biological Progression-Free Survival","time_frame":"Assessed from randomization up to study completion up to 6.6 years.","description":"Defined as the time from randomization to the earlier date of assessment of biological progression evaluated by increasing CA 125 levels or death due to any cause in the absence of progression."},{"outcome_type":"secondary","measure":"Safety Assessments: NCI CTCAE version 5.0","time_frame":"Assessed from Screening through 30 days after the completion of Investigational Medicinal Product approximately 18 months.","description":"Defined as the incidence, severity and outcome of treatment emergent adverse events (TEAEs), and serious adverse events (SAEs) assessed by NCI CTCAE version 5.0."}]}
{"nct_id":"NCT04869943","start_date":"2021-09-30","phase":"Phase 3","enrollment":210,"brief_title":"Efficacy Evaluation of Enobosarm Monotherapy in Treatment of AR+/ER+/HER2- Metastatic Breast Cancer","official_title":"Randomized Phase 3 Efficacy Evaluation of Enobosarm Monotherapy vs Control Treatment of AR+/ER+/HER2- MBC in Patients With AR Nuclei Staining 40% Who Has Shown Disease Progression on a Nonsteroidal AI Fulvestrant and CDK 4/6 Inhibitor.","primary_completion_date":"2023-03-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-04-30","last_update":"2021-09-20","description":"To demonstrate the efficacy of enobosarmin the treatment of androgen receptor positive (AR+) and estrogen receptor positive (ER+) metastatic breast cancer (MBC) as measured by radiographic progression free survival (rPFS).","other_id":"V3002401","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Subjects in the Enobosarm Treatment Group will receive enobosarm 9mg each day by mouth until disease progression or an unacceptable adverse event is observed. Subjects in the Control Treatment Group will receive a ER targeted therapy limited to exemestane monotherapy, exemestane plus everolimus or selective estrogen receptor modulator(SERM) approved for the treatment of breast cancer and is part of the standard of care at the clinical study site. The decision of which comparator treatment will be used will be made prior to randomization.","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":100,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Provide informed consent\r\n\r\n          -  Be able to communicate effectively with the study personnel\r\n\r\n          -  Aged 18 years\r\n\r\n          -  For Female Subjects\r\n\r\n               -  Menopausal status\r\n\r\n          -  Be postmenopausal as defined by the National Comprehensive Cancer Network as either:\r\n\r\n               -  Age 55 years and one year or more of amenorrhea\r\n\r\n               -  Age <55 years and one year or more of amenorrhea, with an estradiol assay <20\r\n                  pg/mL\r\n\r\n               -  Age <55 years and surgical menopause with bilateral oophorectomy\r\n\r\n          -  Be premenopausal or perimenopausal on ovarian suppression with LHRH agonist for at\r\n             least 4 months, with an estradiol assay <20 pg/mL and a negative urine pregnancy test.\r\n\r\n          -  If subject is of child bearing potential, the subject must agree to use acceptable\r\n             methods of contraception:\r\n\r\n               -  If female study participant could become pregnant, use acceptable methods of\r\n                  contraception from the time of the first administration of study medication until\r\n                  6 months following administration of the last dose of study medication.\r\n                  Acceptable methods of contraception are as follows: Condom with spermicidal\r\n                  foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical\r\n                  sterilization of male partner (vasectomy with documentation of azoospermia) and a\r\n                  barrier method {condom used with spermicidal foam/gel/film/cream/suppository}\r\n\r\n               -  If female study participant has undergone documented tubal ligation (female\r\n                  sterilization), a barrier method (condom used with spermicidal\r\n                  foam/gel/film/cream/suppository) should also be used\r\n\r\n               -  If female study participant has undergone documented placement of an intrauterine\r\n                  device (IUD) or intrauterine system (IUS), a barrier method (condom with\r\n                  spermicidal foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  For Male Subjects\r\n\r\n               -  Subject must agree to use acceptable methods of contraception:\r\n\r\n          -  If the study subject's partner could become pregnant, use acceptable methods of\r\n             contraception from the time of the first administration of study medication until 6\r\n             months following administration of the last dose of study medication. Acceptable\r\n             methods of contraception are as follows: Condom with spermicidal foam/gel/\r\n             film/cream/suppository [i.e., barrier method of contraception], surgical sterilization\r\n             (vasectomy with documentation of azoospermia) and a barrier method {condom used with\r\n             spermicidal foam/gel/film/cream/suppository}, the female partner uses oral\r\n             contraceptives (combination estrogen/progesterone pills), injectable progesterone or\r\n             subdermal implants and a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository)\r\n\r\n          -  If female partner of a study subject has undergone documented tubal ligation (female\r\n             sterilization), a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  If female partner of a study subject has undergone documented placement of an\r\n             intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with\r\n             spermicidal foam/gel/film/cream/suppository) should also be used\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2\r\n\r\n          -  Documented evidence of ER+/HER2- metastatic breast cancer\r\n\r\n          -  Measurable disease is required as per RECIST 1.1 (NOTE: Bone only metastatic disease\r\n             is acceptable but requires a measurable component\r\n\r\n          -  Have androgen receptor nuclei staining 40% as assessed by central laboratory\r\n\r\n          -  Received at least 2 prior lines of treatment in MBC setting which must have included\r\n             both an AI (monotherapy or combination) and fulvestrant (monotherapy or combination);\r\n             at least one must have been given in combination with a CDK 4/6 inhibitor.\r\n\r\n          -  Previously responded (without disease progression for at least 6 months) to one of the\r\n             following treatments: fulvestrant monotherapy or fulvestrant plus CDK 4/6 inhibitor or\r\n             nonsteroidal aromatase inhibitor monotherapy or nonsteroidal aromatase inhibitor plus\r\n             CDK 4/6 inhibitor for metastatic breast cancer.\r\n\r\n          -  Subject is willing to comply with the requirements of the protocol through the end of\r\n             the study\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known hypersensitivity or allergy to enobosarm\r\n\r\n          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 X upper limit\r\n             of normal (ULN) or total bilirubin >ULN (an elevated total bilirubin up to 1.5 X ULN\r\n             attributed to a previously confirmed diagnosis of Gilbert's disease is acceptable if\r\n             all other eligibility criteria are met). In patients with documented metastases to the\r\n             liver, the limits for inclusion are ALT or AST >5.0 X ULN or total bilirubin >1.5 X\r\n             ULN.\r\n\r\n          -  Patients with biliary catheter.\r\n\r\n          -  Creatinine clearance < 30 mL/min as measured using the Cockcoft Gault formula\r\n             (patients with mild and moderate renal failure are not excluded from participation in\r\n             this study)\r\n\r\n          -  Previously received >1 course of systemic chemotherapy (not including immunotherapies\r\n             or targeted therapies) for the treatment of metastatic breast cancer.\r\n\r\n        Note: Subjects may have received 1 course of chemotherapy in the adjuvant or neoadjuvant\r\n        setting would not count as a line of therapy.\r\n\r\n          -  Subjects with radiographic evidence of central nervous system (CNS) metastases as\r\n             assessed by CT or MRI that are not well-controlled (symptomatic or requiring control\r\n             with continuous corticosteroid therapy [e.g., dexamethasone]) Note: Subjects with CNS\r\n             metastases are permitted to participate in the study if the CNS metastases are\r\n             medically well-controlled and stable for at least 30 days after receiving local\r\n             therapy (irradiation, surgery, etc.)\r\n\r\n          -  Radiotherapy within 14 days prior to randomization except in case of localized\r\n             radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can\r\n             then be completed within 7 days prior to randomization. Subjects must have recovered\r\n             from radiotherapy toxicities prior to randomization\r\n\r\n          -  Any comorbid disease or condition (medical or surgical) which might compromise the\r\n             hematologic, cardiovascular, endocrine, pulmonary, severe renal impairment,\r\n             gastrointestinal, hepatic, or central nervous system; or other conditions that may\r\n             interfere with the absorption, distribution, metabolism or excretion of study drug, or\r\n             would place the subject at increased risk\r\n\r\n          -  Treatment with any investigational product within < 4 half-lives for each individual\r\n             investigational product OR within 30 days prior to randomization\r\n\r\n          -  Major surgery within 30 days prior to randomization\r\n\r\n          -  Treatment with testosterone, methyltestosterone, oxandrolone (Oxandrin),\r\n             oxymetholone, danazol, fluoxymesterone (Halotestin), testosterone-like agents (such\r\n             as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including\r\n             herbals), or antiandrogens (enzalutamide, abiraterone, bicalutamide, apalutamide, or\r\n             darolutamide). Previous therapy with testosterone and testosterone-like agents is\r\n             acceptable with a 30-day washout (if previous testosterone therapy was long term depot\r\n             within the past 6 months, the site should contact the Medical Monitor) or any other\r\n             androgenic agent.\r\n\r\n          -  Treatment with any of the following hormone replacement therapies for metastatic\r\n             breast cancer. Prior use in the adjuvant or neoadjuvant setting is allowed if the\r\n             treatment is, discontinued greater than 30 days prior to randomization\r\n\r\n               -  Estrogens\r\n\r\n               -  Megesterol acetate\r\n\r\n               -  Testosterone\r\n\r\n          -  All other concurrent anticancer treatments (including, but not limited to, all SERMs\r\n             unless randomized to the Control Treatment Group with a SERM as the control treatment,\r\n             AIs unless randomized to Control Treatment Group (exemestane or exemestane plus\r\n             everolimus) with the AI containing treatment as the control treatment, and all CDK 4/6\r\n             inhibitors)\r\n\r\n          -  An abnormal ECG result which, based on the investigator's clinical judgment, would\r\n             place the subject at increased risk\r\n\r\n          -  Has a known additional, invasive, malignancy that is progressing or required active\r\n             treatment in the last 5 years [note: subjects with basal cell carcinoma of the skin,\r\n             squamous cell carcinoma of the skin, ductal breast carcinoma in situ, bladder cancer\r\n             (superficial treated), or cervical carcinoma in situ that have undergone potentially\r\n             curative therapy are not excluded]\r\n\r\n          -  Pregnant, lactating, or breastfeeding, or intending to become pregnant during the\r\n             study or within 60 days after the final dose of study treatment\r\n      ","sponsor":"Veru Inc.","sponsor_type":"Industry","conditions":"Metastatic Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Enobosarm","description":"Oral Enobosarm 9mg per day"},{"intervention_type":"Drug","name":"Drug: Exemestane","description":"Exemestane monotherapy, exemestane plus everolimus, or selective estrogen receptor modulator (SERM)"}],"outcomes":[{"outcome_type":"primary","measure":"To demonstrate the efficacy of Enobosarm in the treatment of androgen receptor positive (AR+) and estrogen receptor positive (ER+) metastatic breast cancer (MBC) as measured by radiographic progression free survival (rPFS).","time_frame":"Day 120","description":"The primary endpoint for the study is the median radiographic progression free survival (rPFS) in the Enobosarm Treatment Group compared to the Control Treatment Group.\r\nProgression will be defined based on RECIST 1.1."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Day 180","description":"Objective Response Rate (ORR), proportion of subjects with a best tumor response of ORR (PR or CR) on study"}]}
{"nct_id":"NCT05007236","start_date":"2021-09-30","phase":"Phase 2","enrollment":204,"brief_title":"Study to Evaluate the Efficacy and Safety of Oral RP7214, a DHODH Inhibitor, in Patients With Symptomatic Mild COVID-19 Infection.","official_title":"A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Oral RP7214, a DHODH Inhibitor, in Patients With Symptomatic Mild SARS-CoV-2 Infection.","primary_completion_date":"2021-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-02-28","last_update":"2021-09-22","description":"This is a randomized, double-blind, placebo-controlled study of RP7214 in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., age > 60 years, hypertension, diabetes mellitus, chronic lung disease, chronic kidney disease, liver disease, cerebrovascular disease, obesity, cancer) for developing severe Covid-19 illness.","other_id":"RP7214-2101","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Willing and able to provide informed consent.\r\n\r\n          2. Males and females of  18 years of age\r\n\r\n          3. Patient with mild COVID-19 infection having  1 symptoms.\r\n\r\n          4. Laboratory confirmed Covid-19 infection by Reverse Transcription Polymerase Chain\r\n             Reaction (RT-PCR) in nasopharyngeal sample (within 72 hours prior to randomization).\r\n\r\n          5. Patient should have at least one pre-existing high-risk feature for developing severe\r\n             Covid-19 illness.\r\n\r\n          6. Ability to swallow and retain oral medication.\r\n\r\n          7. Male patient who is surgically sterile, or who is willing to agree to use a\r\n             contraceptive measure.\r\n\r\n          8. Women of childbearing potential should be willing to use a medically acceptable method\r\n             of contraception.\r\n\r\n          9. Willing to receive telephone calls or have videoconferences with study team personnel.\r\n\r\n         10. Willing and able to understand the nature of this study, comply with the study\r\n             procedures and follow-up procedures as per the study protocol.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Patient with asymptomatic Covid-19 infection.\r\n\r\n          2. Patient who has experienced the onset of any of Covid-19 symptoms > 5 days at the time\r\n             of randomization.\r\n\r\n          3. Moderate to Severe COVID-19 infection\r\n\r\n          4. Patient with Covid-19 re-infection\r\n\r\n          5. Subjects who are severely immunocompromised\r\n\r\n          6. Subjects with autoimmune diseases\r\n\r\n          7. Patients with any bleeding disorder e.g., hemophilia and von Willebrand disease.\r\n\r\n          8. Current use of other DHODH inhibitors including teriflunomide or leflunomide.\r\n\r\n          9. Patients who are on or immediately require Covid-19 directed treatment such as\r\n             antivirals, immunomodulatory treatment, convalescent plasma, oral/ intravenous\r\n             steroids, or monoclonal antibodies at the time of screening.\r\n\r\n         10. Patients who have had received one or two doses of vaccine for Covid-19.\r\n\r\n         11. Patients participating in another clinical study or use of any investigational product\r\n             within 4 weeks or 5 half-lives of the drug, whichever is longer, before the date of\r\n             dosing\r\n      ","sponsor":"Rhizen Pharmaceuticals SA","sponsor_type":"Industry","conditions":"SARS-CoV-2 Infection","interventions":[{"intervention_type":"Drug","name":"Drug: RP7214 + Standard of care (SOC)","description":"RP7214 tablets will be administered orally twice a day for 14 days"},{"intervention_type":"Drug","name":"Drug: Placebo + Standard of care (SOC)","description":"Placebo will be administered orally twice a for 14 days"}],"outcomes":[{"outcome_type":"primary","measure":"Proportion of patients requiring Covid-19 related hospitalization by Day 15.","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Change from baseline in SARS-CoV-2 viral load at Days 3, 7 and 15 by quantitative RT-PCR test","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Time to symptom resolution in patients receiving RP7214 as compared to placebo","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Proportion of patients demonstrating symptom resolution","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Time to symptom improvement in patients receiving RP7214 as compared to placebo","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Proportion of patients demonstrating symptom improvement","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Adverse Events (AEs) as assessed by laboratory tests, vital signs and physical examination.","time_frame":"15 days"},{"outcome_type":"secondary","measure":"Change in the disease-specific inflammatory markers (Ferritin, C-reactive protein (CRP), D-dimer, neutrophil to lymphocyte/CD8+ ratio, LDH, IL-6) as compared to baseline.","time_frame":"15 days"}]}
{"nct_id":"NCT04999969","start_date":"2021-09-27","phase":"Phase 2","enrollment":115,"brief_title":"Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours","official_title":"A Phase II Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumours","primary_completion_date":"2023-11-28","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-11-28","last_update":"2021-08-11","description":"The proposed study is designed to examine the effects of AZD0171 and durvalumab in combination with standard-of-care chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).","other_id":"D8151C00001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1 at screening/enrolment\r\n\r\n          -  Must have a Gustave Roussy Immune Score of 0 or 1\r\n\r\n          -  Participants diagnosed with histologically confirmed pancreatic adenocarcinoma\r\n\r\n          -  Participants must have at least 1 measurable lesion to be called a target lesion\r\n             according to RECIST v1.1\r\n\r\n          -  All participants must consent to providing sufficient archival specimen taken during\r\n             metastatic stage or fresh tumour specimens for tumoural CD8+ T cell testing for\r\n             enrolment\r\n\r\n          -  Presence of tumoural CD8+ T cells based on a predetermined benchmarked PDAC external\r\n             sample\r\n\r\n          -  Normal organ and bone marrow function measured within 28 days prior to first dose of\r\n             study intervention\r\n\r\n          -  Body weight  35 kg\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Symptomatic central nervous system metastasis or any history of leptomeningeal disease\r\n             or cord compression\r\n\r\n          -  A participant with an already known sensitising mutation or tumour characteristic for\r\n             pancreatic cancer for which there is a preferred local standard-of-care treatment\r\n\r\n          -  History of thromboembolic event within the past 3 months prior to the scheduled first\r\n             dose of study intervention\r\n\r\n          -  Any unresolved toxicities  Grade 2 per Common Terminology Criteria for Adverse Events\r\n             v5.0 from prior therapy (excluding vitiligo, alopecia, controlled diabetes)\r\n\r\n          -  History of solid organ transplantation\r\n\r\n          -  History of active primary immunodeficiency\r\n\r\n          -  Ongoing or an active infection, including tuberculosis, hepatitis B, hepatitis C, or\r\n             human immunodeficiency virus. For Coronavirus disease 2019 (COVID-19) infections, a\r\n             negative polymerase chain reaction test is required\r\n\r\n          -  Uncontrolled intercurrent illness\r\n\r\n          -  Participants with prior history of myocardial infarction, transient ischemic attack,\r\n             coronary bypass, or stroke within the past 3 months prior to the first dose of study\r\n             intervention\r\n\r\n          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) 470 ms\r\n             calculated from 3 electrocardiograms\r\n\r\n          -  Active or prior documented autoimmune or inflammatory disorders\r\n\r\n          -  History of another primary malignancy\r\n\r\n          -  Receipt of any conventional or investigational anticancer therapy prior to the\r\n             scheduled first dose of study intervention\r\n\r\n          -  Prior receipt of any immune-mediated therapy\r\n\r\n          -  Use of immunosuppressive medication within 14 days prior to the first dose of study\r\n             intervention\r\n\r\n          -  Receipt of live, attenuated vaccine within 28 days prior to the first dose of study\r\n             intervention (Participants can receive non-live COVID-19 vaccines, at the discretion\r\n             of the Investigator)\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Locally Advanced or Metastatic Solid Tumours","interventions":[{"intervention_type":"Drug","name":"Drug: AZD0171","description":"AZD0171"},{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"Durvalumab"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Chemotherapy (Standard-of-Care)"},{"intervention_type":"Drug","name":"Drug: Nab-paclitaxel","description":"Chemotherapy (Standard-of-Care)"}],"outcomes":[{"outcome_type":"primary","measure":"Number of participants with adverse events (AEs), immune mediated AEs (imAEs) and serious AEs (SAEs)","time_frame":"Until Day 90 (post last dose of study intervention on Day 15)","description":"Assessment of safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy)."},{"outcome_type":"primary","measure":"Overall survival at 12 months (OS-12)","time_frame":"Up to 12 months","description":"Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"Up to 24 months","description":"Assessment of efficacy of study intervention according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) using investigator assessment of disease response. The percentage of response evaluable participants with a confirmed response of complete response (CR) or partial response (PR)."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Up to 24 months","description":"Assessment of the efficacy of study intervention according to RECIST v1.1. The DCR is defined as the percentage of participants according to RECIST v1.1 with a confirmed response or stable disease maintained for 16 weeks."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Up to 24 months","description":"Assessment of the efficacy of study intervention according to RECIST 1.1. The DoR is defined as the time from first documented response until date of documented disease progression or death."},{"outcome_type":"secondary","measure":"Median progression free survival (PFS)","time_frame":"Up to 24 months","description":"PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death."},{"outcome_type":"secondary","measure":"PFS at 4 months (PFS-4)","time_frame":"4 months","description":"Percentage of participants with PFS at 4 months per Kaplan-Meier estimate of PFS."},{"outcome_type":"secondary","measure":"Median overall survival (OS)","time_frame":"Up to 24 months","description":"OS is defined as the time from the start of study intervention to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Number of participants with change from Baseline in serum levels of carbohydrate antigen 19-9 (CA19-9)","time_frame":"From Screening (Day -28 to Day -1) until Day 28 post last dose of study intervention on Day 15","description":"Percentage change in local laboratory assessed serum CA19-9 from baseline."},{"outcome_type":"secondary","measure":"Number of participants developing detectable anti-drug antibodies (ADAs) against AZD0171 and/or durvalumab in serum","time_frame":"Up to Day 90 post last dose of study intervention on Day 15","description":"Immunogenicity of AZD0171 and/or durvalumab will be assessed."},{"outcome_type":"secondary","measure":"The PK profile of AZD0171, durvalumab and chemotherapy- Maximum observed plasma concentration (Cmax)","time_frame":"At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15","description":"The PK profile of AZD0171, total leukaemia inhibitory factor (LIF), durvalumab and chemotherapies and/or their metabolites will be determined."},{"outcome_type":"secondary","measure":"The PK profile of AZD0171, durvalumab and chemotherapy - Area under the concentration-time curve (AUC)","time_frame":"At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15","description":"The PK profile of AZD0171, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined."},{"outcome_type":"secondary","measure":"The PK profile of AZD0171, durvalumab and chemotherapy - Clearance (CL)","time_frame":"At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15","description":"The PK profile of AZD0171, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined."},{"outcome_type":"secondary","measure":"The PK profile of AZD0171, durvalumab and chemotherapy - Terminal elimination half-life (t1/2)","time_frame":"At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15","description":"The PK profile of AZD0171, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined."},{"outcome_type":"secondary","measure":"Participants with changes from Baseline in cluster of differentiation 8 (CD8+) T cell tumour infiltration in tumour samples","time_frame":"Up to 24 months","description":"The changes in CD8+ T cell tumour infiltration associated with AZD0171 treatment in combination with durvalumab and chemotherapy will be assessed in participants with 1L mPDAC."}]}
{"nct_id":"NCT05008445","start_date":"2021-09-23","phase":"Phase 1/Phase 2","enrollment":265,"brief_title":"Study of LM-102 in Patients With Advance Solid Tumors","official_title":"A Phase I/II, Open-Label, Multiple Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM-102 Monotherapy or Combination Therapy in Patients With CLDN18.2-Positive Advanced Solid Tumors","primary_completion_date":"2025-03-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-06-30","last_update":"2021-08-17","description":"This is an open label Phase I/II trial of LM-102 injection, a recombinant humanized monoclonal antibody targeting Claudin 18.2 (CLDN18.2). It is being tested in advanced solid tumors including gastric cancer/gastroesophageal junction adenocarcinoma, Pancreatic Cancer, Biliary Tract Cancer, esophageal adenocarcinoma and ovarian mucous carcinoma.","other_id":"LM102-01-102","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Subjects will be enrolled into the study only if they meet all of the following inclusion\r\n        criteria:\r\n\r\n          1. Subjects who are fully informed of the purpose, nature, method and possible adverse\r\n             reactions of the study, and are willing to participate in the study and sign the\r\n             informed consent document prior to any procedure;\r\n\r\n          2. Aged between 18 to 75 years old, male or female when sign the Informed consent form\r\n             (ICF);\r\n\r\n          3. Subjects who meet the criteria:\r\n\r\n             Phase I dose escalation:\r\n\r\n             Part Ia: Subjects have histological or cytological confirmation of recurrent or\r\n             refractory advanced solid tumors, and are intolerable for available standard therapy,\r\n             or there is no available standard therapy.\r\n\r\n             Part Ib:Subjects have been histologically or cytologically confirmed advanced solid\r\n             tumors and meet the criteria as follows: No previous systemic chemotherapy was given\r\n             for the recurrent or metastatic disease or for the subjects who have received curative\r\n             treatment (including neo-adjuvant or adjuvant chemotherapy /radiotherapy, etc.), the\r\n             interval between recurrence and the last dose of previous anti-cancer treatment must\r\n             be more than 6 months.\r\n\r\n             Phase II dose expansion: subjects with positive CLDN18.2 confirmed by central\r\n             immunohistochemistry (IHC).\r\n\r\n             Part IIa: Subjects have histological or cytological confirmation of recurrent or\r\n             refractory advanced solid tumors, and are intolerable for available standard therapy,\r\n             or there is no available standard therapy.\r\n\r\n             Part IIb: Subjects have histological or cytological confirmation of advanced solid\r\n             tumors and meet the criteria as follows: No previous systemic chemotherapy was given\r\n             for the recurrent or metastatic disease, or for the subjects who have received\r\n             curative treatment (including neo-adjuvant or adjuvant chemotherapy /radiotherapy,\r\n             etc.), the interval between recurrence and the last dose of previous anti-cancer\r\n             treatment must be more than 6 months;\r\n\r\n          4. At least one evaluable lesion for phase I and one measurable lesion for phase II\r\n             according to RECIST v1.1;\r\n\r\n          5. ECOG score 0-1;\r\n\r\n          6. Life expectancy  3 months;\r\n\r\n          7. Subjects must have the following organ and marrow function in laboratory tests within\r\n             7 days prior to the first dose;\r\n\r\n          8. Subjects who are able to well communicate with investigators as well as understand and\r\n             adhere to the requirements of this study.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Subjects will be excluded from the study, if they meet any of the following criteria:\r\n\r\n          1. Child-bearing potential female who have positive results in pregnancy test or are\r\n             lactating;\r\n\r\n          2. Subjects who known to be allergic to the similar products or any of its excipients;\r\n\r\n          3. Exposure to any IMP, or participate in any other clinical trial within 21 days prior\r\n             to 1st dosing of LM-102;\r\n\r\n          4. Subjects with anti-tumor treatment within 28 days prior to 1st dosing of LM-302,\r\n             including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy,\r\n             etc.\r\n\r\n          5. Subjects who have received surgical or interventional treatment within 28 days prior\r\n             to 1st dosing LM-102, with the exception for tumor biopsy, puncture, etc.;\r\n\r\n          6. Subjects who have received the treatment targeting to CLDN18.2 or ADCs;\r\n\r\n          7. Use of any live vaccines (e.g., against infectious diseases such as influenza,\r\n             varicella etc.) within 28 days prior to 1st dosing of LM-102;\r\n\r\n          8. Subjects with the history of interstitial lung disease or drug-induced interstitial\r\n             lung disease/pneumonitis;\r\n\r\n          9. Subjects who are taking therapeutic doses of anticoagulants such as heparin or vitamin\r\n             K antagonists (except for preventive treatment at a stable dose);\r\n\r\n         10. Subjects with gastric outlet obstruction, persistent recurrent vomiting or\r\n             uncontrolled/severe gastrointestinal hemorrhage, or ulcer within 28 days prior to 1st\r\n             dosing;\r\n\r\n         11. Subjects who are unable to take the oral drugs, have the conditions that severely\r\n             affect gastrointestinal absorption;\r\n\r\n         12. Subjects with known central nervous system (CNS) or meningeal metastasis;\r\n\r\n         13. Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites\r\n             requiring recurrent drainage procedures;\r\n\r\n         14. Subjects who have severe cardiovascular disease;\r\n\r\n         15. Any adverse event from prior anti-tumor therapy has not yet recovered to  grade 1 of\r\n             CTCAE v5.0;\r\n\r\n         16. Subjects with uncontrolled tumor-related pain.\r\n\r\n         17. Subjects who have uncontrolled or severe illness, including but not limited to ongoing\r\n             or active infection requiring antibiotics administration;\r\n\r\n         18. Subjects who have a history of immunodeficiency disease, including other acquired or\r\n             congenital immunodeficiency diseases, or organ transplantation, or allogeneic bone\r\n             marrow transplantation, or autologous hematopoietic stem cell transplantation;\r\n\r\n         19. HIV infection, active HBV and HCV infection;\r\n\r\n         20. Men and women who are unwilling to use appropriate contraceptive methods throughout\r\n             the study period and for at least 6 months after the last use of LM-102;\r\n\r\n         21. Subjects who have psychiatric illness or social situations that would preclude study\r\n             compliance;\r\n\r\n         22. Subjects who have another active malignancy which is likely to require treatment, and\r\n             have the history of another malignancy within 2 years before the first dosing;\r\n\r\n         23. Subject who is determined as not eligible to participate in this study by the\r\n             investigator.\r\n      ","sponsor":"LaNova Medicines Development Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Solid Tumor","interventions":[{"intervention_type":"Biological","name":"Biological: LM-102 Injection","description":"LM-102 Injection with dose escalation stage of 3mg/kg up to 40mg/kg, as well as dose expansion stage with recommended dose level from dose escalation stage."},{"intervention_type":"Combination Product","name":"Combination Product: LM-102 Injection combined with SOC","description":"LM-102 Injection with appropriate dose level(s), combined with SOC."}],"outcomes":[{"outcome_type":"primary","measure":"The incidence and case number of DLT (Dose Limiting Toxicity) during observation period","time_frame":"up to 21 days following first dose","description":"DLT is short for Dose Limiting Toxicity. dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment."},{"outcome_type":"primary","measure":"Participant Safety as characterized by frequency and severity of adverse events(according to NCI CTCAE 5.0)","time_frame":"up to 31 days following last dose or other anti-cancer therapy","description":"An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product."},{"outcome_type":"primary","measure":"Recommended Phase II Dose (RP2D)","time_frame":"up to 21 days following first dose","description":"The RP2D will be determined during the dose expansion stage of the study. RP2D will be determined using available safety and efficacy data."},{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD）","time_frame":"up to 21 days following first dose","description":"The MTD is defined as the dose of which the toxicity rate is lower than the upper bound of EI p_T+ϵ_1= 0.35 and closest to the target toxicity rate of p_T= 0.3 during the DLT observation period (21 days after the first administration in cycle 1 on day 1)."},{"outcome_type":"secondary","measure":"Area under plasma concentration vs time curve (AUC) for LM-102","time_frame":"Up to finished circle 5 (each cycle is 21 days)","description":"changes in AUC over time in participants with LM-102"},{"outcome_type":"secondary","measure":"Peak plasma concentration (Cmax) for LM-102","time_frame":"Up to finished circle 5 (each cycle is 21 days)","description":"Cmax is the maximum plasma concentration."},{"outcome_type":"secondary","measure":"Time to maximum observed plasma concentration (Tmax)","time_frame":"Up to finished circle 5 (each cycle is 21 days)","description":"Tmax is the time in hrs/days it takes to reach Cmax after dosing with LM-102"},{"outcome_type":"secondary","measure":"Terminal elimination half life (t1/2)","time_frame":"Up to finished circle 5 (each cycle is 21 days)","description":"Time for the plasma level of LM-102 to decrease by 1/2 during the terminal elimination phase"},{"outcome_type":"secondary","measure":"Immunogenicity","time_frame":"up to 31 days following last dose","description":"by measurement of Incidence of anti-drug antibodies (ADA)"},{"outcome_type":"secondary","measure":"Disease Control Rate(DCR )","time_frame":"through study completion, an average of 8 months.","description":"as measured by RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"through study completion, an average of 8 months.","description":"as measured by RECIST v1.1"},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"through study completion, an average of 8 months.","description":"as measured by RECIST v1.1"}]}
{"nct_id":"NCT04958239","start_date":"2021-09-22","phase":"Phase 1","enrollment":150,"brief_title":"A Study to Test Different Doses of BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors)","official_title":"An Open Label, Phase I Dose-finding Study of BI 765179 as Monotherapy and in Combination With Ezabenlimab (BI 754091) in Patients With Advanced Solid Cancers","primary_completion_date":"2024-03-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-01-02","last_update":"2021-09-08","description":"This study is open to adults with advanced cancer (solid tumors). People for whom previous treatment was not successful can take part in this study. The purpose of this study is to find the highest dose of a medicine called BI 765179 that people with solid tumors can tolerate when taken alone or together with a medicine called ezabenlimab. Each participant is put into one of two groups. Participants get BI 765179 alone or in combination with ezabenlimab as infusion into a vein every 3 weeks. BI 765179 and ezabenlimab are antibodies that may help the immune system fight cancer. In this study, BI 765179 is given to people for the first time. Participants can stay in the study up to 3 years if they benefit from treatment and can tolerate it. The doctors regularly check the participants' health and note any health problems that could have been caused by the study treatment.","other_id":"1463-0001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  All cohorts:\r\n\r\n          -  Patients with locally advanced, unresectable or metastatic solid tumors who are either\r\n             refractory after standard therapy for the disease or for whom standard therapy is not\r\n             appropriate\r\n\r\n          -  Tumor with expected high expression of Fibroblast activation protein (FAP) of the\r\n             following histologies:\r\n\r\n               -  Non-small cell lung carcinoma (NSCLC)\r\n\r\n               -  Gastric cancer\r\n\r\n               -  Esophageal adenocarcinoma or squamous cell carcinoma\r\n\r\n               -  Urothelial bladder carcinoma\r\n\r\n               -  Oral squamous cell cancer\r\n\r\n               -  Cutaneous malignant melanoma\r\n\r\n               -  Hepatocellular carcinoma\r\n\r\n               -  Pancreatic adenocarcinoma\r\n\r\n               -  Colorectal cancer\r\n\r\n               -  Malignant pleural mesothelioma\r\n\r\n               -  Cervical squamous cell cancer\r\n\r\n               -  Ovarian carcinoma\r\n\r\n          -  At least 18 years of age at the time of the consent or over the legal age of consent\r\n             in countries where that is greater than 18 years\r\n\r\n          -  Signed and dated, written informed consent (IC) in accordance with ICH-GCP and local\r\n             legislation prior to to admission to the trial\r\n\r\n          -  At least one measurable lesion outside of central nervous system (CNS) as defined per\r\n             modified Response evaluation criteria in solid tumors (RECIST) 1.1\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  Adequate liver, bone marrow and renal organ function\r\n\r\n          -  Male or female patients. Women of childbearing potential (WOCBP)1 and men able to\r\n             father a child must be ready and able to use highly effective methods of birth control\r\n             per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used\r\n             consistently and correctly. These methods must be used during the study and for at\r\n             least 6 months after the last dose of the study medication. A list of contraception\r\n             methods meeting these criteria is provided in the patient information.\r\n\r\n          -  Patients with brain metastases are eligible provided they meet all of the following\r\n             criteria:\r\n\r\n               -  brain metastases have adequately been treated and are considered stable by the\r\n                  Investigator\r\n\r\n               -  radiotherapy or surgery for brain metastases was completed at least 2 weeks prior\r\n                  to the first administration of BI 765179\r\n\r\n               -  patient is off steroids for at least 7 days (physiologic doses of steroids is\r\n                  permitted, if this was stable for the last 4 weeks)\r\n\r\n               -  the patient is off anti-epileptic drugs for at least 7 days\r\n\r\n        Back-fill cohorts only:\r\n\r\n          -  Patient has agreed to and signed an informed consent (IC) form to provide mandatory\r\n             pre-treatment and on-treatment fresh tumor biopsy\r\n\r\n          -  At least one lesion (separate from the evaluable target lesion outside of the CNS as\r\n             defined per RECIST v1.1) that is accessible for mandatory paired pre and on-treatment\r\n             biopsy\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Currently enrolled in another investigational device or drug trial\r\n\r\n          -  Previous or concomitant malignancies other than the one treated in this trial within\r\n             the last 2 years except:\r\n\r\n               -  effectively treated non-melanoma skin cancers\r\n\r\n               -  effectively treated carcinoma in situ of the cervix\r\n\r\n               -  effectively treated ductal carcinoma in situ\r\n\r\n               -  other effectively treated malignancy that is considered cured by 'local\r\n                  treatment'\r\n\r\n          -  Previous treatment with agents targeting CD137\r\n\r\n          -  Known leptomeningeal disease or spinal cord compression due to disease\r\n\r\n          -  Anticoagulant treatment that cannot be safely interrupted if medically needed (e.g.,\r\n             biopsy) based on the opinion of the Investigator\r\n\r\n          -  Persistent toxicity from previous treatments that has not resolved to  Common\r\n             terminology criteria for adverse events (CTCAE) Grade 1 (except for alopecia, CTCAE\r\n             Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by\r\n             replacement therapy)\r\n\r\n          -  Patient has a diagnosis of immunodeficiency\r\n\r\n          -  Patient with history of immunosuppressive medication within 14 days prior to the first\r\n             dose of BI 765179. The following are exceptions to this criterion:\r\n\r\n               -  Use of intranasal, inhaled, or topical corticosteroids, local steroid injections\r\n                  (e.g., intra-articular injections)\r\n\r\n               -  Systemic corticosteroids at physiologic doses 10 mg/day (prednisone or\r\n                  equivalent)\r\n\r\n               -  Physiological replacement dose of corticosteroids\r\n      ","sponsor":"Boehringer Ingelheim","sponsor_type":"Industry","conditions":"Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: BI 765179","description":"BI 765179"},{"intervention_type":"Drug","name":"Drug: Ezabenlimab","description":"Ezabenlimab"}],"outcomes":[{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD)","time_frame":"Up to Day 21 (end of Cycle 1)","description":"MTD is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period. The MTD will be assessed based on the number of patients experiencing DLTs, graded according to Common terminology criteria for adverse events (CTCAE) version 5.0, during the MTD evaluation period."},{"outcome_type":"primary","measure":"Number of patients experiencing Dose Limiting Toxicities (DLTs) in the MTD evaluation period","time_frame":"Up to Day 21 (end of Cycle 1)"},{"outcome_type":"secondary","measure":"Number of patients experiencing DLTs during the on-treatment period (per arm)","time_frame":"up to 36 months"},{"outcome_type":"secondary","measure":"Maximum measured concentration of BI 765179 or ezabenlimab in plasma (Cmax)","time_frame":"Up to Day 21 (end of Cycle 1)"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve of BI 765179 or ezabenlimab in plasma over a uniform dosing interval from zero to 504h (AUC0-504)","time_frame":"Up to Day 21 (end of Cycle 1)"},{"outcome_type":"secondary","measure":"Maximum measured concentration of BI 765179 or ezabenlimab in plasma at steady state (Cmax,ss)","time_frame":"up to Day 84 (end of Cycle 4)"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve of BI 765179 or ezabenlimab in plasma at steady state over a uniform dosing interval 504h (AUC0-504,ss)","time_frame":"Up to Day 84 (end of Cycle 4)"}]}
{"nct_id":"NCT05047536","start_date":"2021-09-20","phase":"Phase 1","enrollment":225,"brief_title":"KZR-261 in Subjects With Advanced Solid Malignancies","official_title":"A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects With Advanced Solid Malignancies","primary_completion_date":"2023-08-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-10-31","last_update":"2021-09-17","description":"A first-in-human, open-label, multicenter, Phase 1 study of KZR-261 designed to assess the safety and tolerability, preliminary anti-tumor activity, and pharmacokinetics (PK) of KZR-261, as well as identify the recommended Phase 2 dose (RP2D). The study comprises a Part 1 (Dose Escalation) and a Part 2 (Dose Expansion) in solid organ tumors (melanoma/uveal melanoma, mesothelioma, colorectal cancer, prostate cancer, and \"all-tumors\").","other_id":"KZR-261-101","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"All subjects will receive 30 to 60-minute intravenous infusion of KZR-261 via a central line on Days 1, 8, and 15 of a 4-week (28-day) treatment cycle.\r\nUp to approximately 50 subjects will be enrolled and treated with KZR-261 in Part 1 (Dose Escalation). In Part 2 (Dose Expansion), up to 175 subjects (15-35 per tumor cohort [melanoma, uveal melanoma, colorectal cancer, prostate cancer, mesothelioma, and \"all-tumor\"]) will be enrolled.","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologic or cytologic evidence of malignant solid tumor with advanced disease\r\n             (except primary central nervous system [CNS] neoplasms), defined as cancer that is\r\n             either metastatic or locally advanced and unresectable (and for which additional\r\n             radiation therapy or other locoregional therapies are not considered to result in\r\n             reasonable clinical benefit).\r\n\r\n          -  Disease that is resistant to or relapsed following available standard systemic\r\n             therapy, or for which there is no standard systemic therapy or reasonable therapy in\r\n             the Investigator's judgment likely to result in clinical benefit, or if such therapy\r\n             has been refused by the subject. Documentation of the reason must be provided for\r\n             subjects who have not received a standard therapy likely to result in clinical\r\n             benefit.\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status score of 0 or 1.\r\n\r\n          -  Adequate baseline hematologic and organ function.\r\n\r\n          -  Willing to use contraception.\r\n\r\n        Additional Inclusion for Part 2: Histologic or cytologic evidence of malignancy\r\n        (melanoma/uveal melanoma, colorectal cancer, prostate cancer, mesothelioma).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects who have participated in Part 1 dose escalation are not eligible to enroll in\r\n             Part 2 dose expansion.\r\n\r\n          -  Persistent clinically significant toxicities from previous anticancer therapy\r\n             (excluding alopecia).\r\n\r\n          -  Treatment with cytotoxic, biologic, or targeted therapies for advanced cancer within\r\n             14 days before administration of the subject's first dose of KZR-261.\r\n\r\n          -  Treatment with an investigational drug within 28 days before administration of the\r\n             subject's first dose of KZR-261.\r\n\r\n          -  Radiation therapy within 14 days of before administration of the subject's first dose\r\n             of KZR-261.\r\n\r\n          -  Major surgical procedure within 28 days before administration of the subject's first\r\n             dose of KZR-261.\r\n\r\n          -  History of risk factors for Torsades de pointes.\r\n\r\n          -  Active, symptomatic CNS metastases or primary CNS malignancy.\r\n\r\n          -  Any female who is breastfeeding or who plans to become pregnant during the study, or\r\n             who are actively trying to conceive at the time of signing of the informed consent\r\n             form (ICF).\r\n\r\n          -  Uncontrolled, clinically significant pulmonary disease.\r\n      ","sponsor":"Kezar Life Sciences, Inc.","sponsor_type":"Industry","conditions":"Advanced/Metastatic Solid Tumor","interventions":[{"intervention_type":"Drug","name":"Drug: KZR-261","description":"KZR-261 for Injection is a lyophilized drug product supplied in single-use vials delivering 75 mg of KZR-261."}],"outcomes":[{"outcome_type":"primary","measure":"Maximum plasma concentration of KZR-261 (Part 1)","time_frame":"Approximately 20 months","description":"Summary of maximum plasma concentration (Cmax) will be assessed"},{"outcome_type":"primary","measure":"Number and percentage of participants experiencing dose-limiting toxicities as assessed by CTCAE v5.0 (Part 1)","time_frame":"Approximately 20 months","description":"Incidence and percentage of dose-limiting toxicities will be collected from start of enrollment"},{"outcome_type":"primary","measure":"Number and percentage of participants experiencing adverse events as assessed by CTCAE v5.0 (Part 1 & 2)","time_frame":"Approximately 20 months","description":"Incidence and percentage of adverse events and serious adverse events will be collected from start of enrollment"},{"outcome_type":"primary","measure":"The plasma concentration time curve of KZR-261 (Part 1)","time_frame":"Approximately 20 months","description":"Summary of the plasma concentration time curve (AUC) will be assessed"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) of KZR-261","time_frame":"Approximately 20 months","description":"Defined as the rate of partial responses (PRs) plus complete responses (CRs) according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR) of KZR-261","time_frame":"Approximately 20 months","description":"Duration of overall response (partial response and complete response)"},{"outcome_type":"secondary","measure":"Progression-free Survival of Patients treated with KZR-261","time_frame":"Approximately 20 months","description":"Time to disease progression"},{"outcome_type":"secondary","measure":"Overall Survival of Patients treated with KZR-261","time_frame":"Approximately 20 months","description":"Time of overall survival"}]}
{"nct_id":"NCT05039944","start_date":"2021-09-20","phase":"Phase 2","enrollment":120,"brief_title":"Efficacy and Safety of SI-B001 as a Single Agent or in Combination With Chemotherapy in the Treatment of Digestive System Malignancies","official_title":"A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 as a Single Agent or in Combination With Chemotherapy in the Treatment of Unresectable or Metastatic Digestive System Malignancies (Colorectal and Gastric Cancer)","primary_completion_date":"2023-09-20","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-09-20","last_update":"2021-09-10","description":"1. Evaluation of effectiveness: To further evaluate the effectiveness of SI-B001 monotherapy RP2D in patients with unresectable or metastatic colorectal cancer and gastric cancer;To evaluate the efficacy of SI-B001 RP2D and sublow dose combined with chemotherapy in patients with unresectable or metastatic colorectal cancer 2. Evaluation of safety and tolerability: To further evaluate the safety and tolerability of SI-B001 single-agent RP2D in patients with unresectable or metastatic colorectal cancer and gastric cancer;To evaluate the safety and tolerability of SI-B001 RP2D and sublow dose combined with chemotherapy in patients with unresectable or metastatic colorectal cancer.","other_id":"SI-B001_211","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Male or female, age 18;\r\n\r\n          2. Expected survival time 3 months;\r\n\r\n          3. Patients with unresectable or metastatic colorectal cancer or gastric cancer confirmed\r\n             by histology or pathology:\r\n\r\n             Cohort_A: Patients with unresectable or metastatic gastric cancer, HER2-negative,\r\n             without standard treatment.\r\n\r\n             Cohort_B: Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal\r\n             cancer, failure of conventional chemotherapy combined with EGFR mab, and withdrawal of\r\n             EGFR mab for less than 3 months.\r\n\r\n             Cohort_C: MSS KRASwt BRAFwt patients with unresectable or metastatic colorectal cancer\r\n             who have failed multiline conventional chemotherapy (without EGFR monoclonal antibody\r\n             therapy).\r\n\r\n             Cohort_D: MSI-H KRASwt BRAFwt patients with unresectable or metastatic colorectal\r\n             cancer and previous first - or second-line treatment failure with anti-PD-1 (L1) mab\r\n             (excluding EGFR mab).\r\n\r\n             Cohort_E: MSI-H KRASwt BRAFwt patients with unresectable or metastatic colorectal\r\n             cancer who have previously failed first-line anti-PD-1 (L1) mab therapy.\r\n\r\n             Cohort_F: MSS KRASwt BRAFwt patients with unresectable or metastatic colorectal cancer\r\n             who have failed standard therapy with first-line oxaliplatin or irinotecan plus\r\n             fluorouracil plus or minus bevacizumab.\r\n\r\n          4. No previous anti-EGFR antibody therapy (excluding Cohort_B);\r\n\r\n          5. Agree to provide 4 specimens (thickness 5m) of tumor tissue specimens (non-stained\r\n             sections (anti-removal)) archiving from primary or metastatic tumors;agree to provide\r\n             6 unstained sections surgical specimens (anti-removal, thickness 10m) or fresh tissue\r\n             samples;\r\n\r\n          6. There must be at least one measurable lesion conforming to the RECIST V1.1 definition;\r\n\r\n          7. Cohort_A, B, C fitness scores 2, Cohort_D, E, F fitness scores 1;\r\n\r\n          8. Toxicity of previous antitumor therapy has been restored to 1 as defined by NCI-CTCAE\r\n             V5.0 (except for toxicity that the researchers judge to be of no safety risk, such as\r\n             hair loss, grade 2 peripheral neurotoxicity, and stabilized hypothyroidism after\r\n             hormone replacement therapy);\r\n\r\n          9. Organ function levels must meet the following requirements and meet the following\r\n             standards:\r\n\r\n             A) Bone marrow function: absolute value of neutrophil count (ANC) 1.5109/L, platelet\r\n             count 100109/L (platelet count 75109/L in Patients with Cohort_A, B and C),\r\n             hemoglobin 90 g/L (hemoglobin 85 g/L in patients with Cohort_A, B and C); B) Liver\r\n             function: Total bilirubin TBIL1.5ULN (total bilirubin TBIL 3ULN in Gilbert's\r\n             syndrome, liver cancer or liver metastases); AST and ALT 2.5ULN in patients without\r\n             liver metastasis; AST and ALT 5.0ULN in patients with liver metastasis; C) Renal\r\n             function: Creatinine (Cr) 1.5ULN, or creatinine clearance (Ccr) 50 mL/min\r\n             (according to Cockcroft and Gault formula); D) Urine routine / 24-hour protein\r\n             quantification: qualitative urine protein 1+ (if qualitative urine protein 2+, 24\r\n             hours < 1g can be included); E) Cardiac function: left ventricular ejection fraction\r\n             50%; F) Coagulation function: International standardized ratio (INR) 1.5ULN, and\r\n             activated partial thrombin time (APTT) 1.5ULN;\r\n\r\n         10. Eligible patients (male and female) who are fertile must agree to use a reliable\r\n             contraceptive method (hormonal or barrier method or abstinence, etc.) with their\r\n             partner during the trial and for at least 6 months after the last medication;Women of\r\n             childbearing age must have a negative blood or urine pregnancy test within 7 days\r\n             prior to the first use of the study drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Colorectal cancer patients with HER2 positive (immunohistochemical +++, or\r\n             immunohistochemical ++ with FISH amplification);\r\n\r\n          2. Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy\r\n             and other anti-tumor therapy within 4 weeks prior to the first use of the study drug,\r\n             except the following:\r\n\r\n             Oral fluorouracil and small molecule targeted drugs are 2 weeks before the first\r\n             administration of the study drug or within the 5 half-lives of the drug (whichever is\r\n             longer); The traditional Chinese medicines with anti-tumor indications were within 2\r\n             weeks before the first use of the study drug;\r\n\r\n          3. Received an unmarketed clinical investigational drug or treatment within 4 weeks prior\r\n             to the first use of the investigational drug;\r\n\r\n          4. Has undergone major organ surgery (excluding needle biopsy, tracheotomy, gastrostomy,\r\n             etc.) or has significant trauma within 4 weeks before the first use of study drugs, or\r\n             needs to undergo elective surgery during the trial;\r\n\r\n          5. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ\r\n             transplantation;\r\n\r\n          6. A history of serious cardiovascular and cerebrovascular diseases, including but not\r\n             limited to:\r\n\r\n             Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias\r\n             requiring clinical intervention, grade iii atrioventricular block, etc.\r\n\r\n             In the resting state, QT interval was prolonged (QTc > 450 msec in men or QTc > 470\r\n             msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection,\r\n             stroke or other grade 3 or higher cardio-cerebrovascular events within 6 months prior\r\n             to the first administration; New York Heart Association (NYHA) heart function grade\r\n             II heart failure;\r\n\r\n          7. Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus,\r\n             inflammatory bowel disease, etc., except type I diabetes, hypothyroidism that can be\r\n             controlled only with replacement therapy, and skin diseases that do not require\r\n             systemic treatment (e.g., vitiligo, psoriasis);\r\n\r\n          8. A history of other malignant tumors within 3 years prior to the first administration,\r\n             with no signs of recurrence and metastasis;\r\n\r\n          9. Poorly controlled hypertension (systolic blood pressure & GT;150 mmHg or diastolic\r\n             pressure &gt;100 mmHg);\r\n\r\n         10. Pulmonary disease defined as grade 3 or higher according to CTCAE V5.0;Patients with\r\n             past or present interstitial lung disease (ILD);\r\n\r\n         11. Cerebral parenchymal or meningeal metastases with clinical symptoms are not suitable\r\n             for inclusion by the investigator;\r\n\r\n         12. Had  grade 3 infusion-related reactions during prior anti-EGFR antibody therapy\r\n             (Cohort_B only);\r\n\r\n         13. There are known allergic contraindications to any excipients of SI-B001 and\r\n             chemotherapeutic agents selected in this study;\r\n\r\n         14. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active\r\n             hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus infection\r\n             (HCV-RNA > center detection lower limit);\r\n\r\n         15. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia,\r\n             sepsis, etc.;\r\n\r\n         16. Pregnant or lactating women;\r\n\r\n         17. Persons with mental disorders or poor compliance;\r\n\r\n         18. The investigator considers that the subject has a history of other serious systemic\r\n             diseases or other reasons and is not suitable to participate in this clinical study.\r\n      ","sponsor":"Sichuan Baili Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SI-B001","description":"Administration by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Irinotecan","description":"Administration by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: FOLFIRI Protocol","description":"Administration by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Folfox Protocol","description":"Administration by intravenous infusion"}],"outcomes":[{"outcome_type":"primary","measure":"ORR","time_frame":"Up to approximately 24 months","description":"Objective Response Rate"},{"outcome_type":"secondary","measure":"PFS","time_frame":"Up to approximately 24 months","description":"Progression-free Survival"},{"outcome_type":"secondary","measure":"DCR","time_frame":"Up to approximately 24 months","description":"Disease Control Rate"}]}
{"nct_id":"NCT05007106","start_date":"2021-09-20","phase":"Phase 2","enrollment":480,"brief_title":"MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005)","official_title":"A Multicenter, Open-label, Phase 2 Basket Study of MK-7684A, a Co-formation of Vibostolimab (MK-7684) With Pembrolizumab (MK-3475), With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors","primary_completion_date":"2025-02-19","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-02-19","last_update":"2021-08-16","description":"The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of pembrolizumab/vibostolimab co-formulation (MK-7684A) with or without other anticancer therapies in participants with selected advanced solid tumors. The primary hypothesis is that pembrolizumab/vibostolimab co-formulation is superior to pembrolizumab alone in terms of objective response rate or progression-free survival in participants with cervical cancer.","other_id":"7684A-005","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Participants with locally recurrent unresectable or metastatic cervical cancer whose tumors express programmed cell death 1 ligand 1 (PD-LI) and have a combined positive score (CPS) 1 will be randomly assigned to treatment with either pembrolizumab/vibostolimab co-formulation or pembrolizumab only. The other study intervention arms will be assigned to participants depending on the selected cancer type.","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  One of the following histologically or cytologically confirmed, advanced (locally\r\n             recurrent unresectable or metastatic) solid tumors:\r\n\r\n               -  Squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix\r\n\r\n               -  Endometrial cancer\r\n\r\n               -  Head and neck swuamous cell carcinoma (HNSCC)\r\n\r\n               -  Unresectable biliary adenocarcinoma (gallbladder or biliary tree [intrahepatic or\r\n                  extrahepatic] cholangiocarcinoma)\r\n\r\n               -  Adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic\r\n                  Siewert type 1 adenocarcinoma of the gastroesophageal junction (GEJ).\r\n\r\n               -  Triple-negative breast cancer (TNBC)\r\n\r\n               -  Hepatocellular carcinoma (HCC)\r\n\r\n          -  Measurable disease per RECIST v1.1 as assessed by BICR or local site investigator.\r\n\r\n          -  Adequately controlled blood pressure (BP) with or without antihypertensive\r\n             medications.\r\n\r\n          -  Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV\r\n             on anti-retroviral therapy (ART).\r\n\r\n          -  Male participants must agree to follow contraceptive guidance.\r\n\r\n          -  Female participants are not pregnant or breastfeeding, not a woman of child-bearing\r\n             potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance.\r\n\r\n          -  Adequate organ function.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of a second malignancy, unless potentially curative treatment has been\r\n             completed with no evidence of malignancy for 3 years.\r\n\r\n          -  Prior therapy with anti-programmed cell-death (PD-1), anti-PD-L1, anti-PD-L2, or\r\n             anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) agent.\r\n\r\n          -  Prior systemic anticancer therapy including investigational agents within 4 weeks\r\n             before randomization/allocation.\r\n\r\n          -  Received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study intervention. Administration of killed vaccines are allowed.\r\n\r\n          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any\r\n             other form of immunosuppressive therapy within 7 days before the first dose of study\r\n             medication.\r\n\r\n          -  Active autoimmune disease that has required systemic treatment in past 2 years.\r\n\r\n          -  Active infection requiring systemic therapy.\r\n\r\n          -  Concurrent active Hepatitis B and Hepatitis C virus infection.\r\n\r\n          -  History of allogenic tissue/solid organ transplant.\r\n\r\n          -  Previous treatment with lenvatinib (for participants who will receive lenvatinib in\r\n             their assigned treatment arm).\r\n\r\n          -  History of congestive heart failure or myocardial infarction within 6 months of\r\n             treatment (for participants who will receive paclitaxel in their assigned allocation\r\n             arm).\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Uterine Cervical Neoplasms|Endometrial Neoplasms|Squamous Cell Carcinoma of Head and Neck|Gallbladder Neoplasms|Cholangiocarcinoma|Esophageal Neoplasms|Triple Negative Breast Neoplasms|Hepatocellular Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Vibostolimab Co-Formulation","description":"Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W"},{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Pembrolizumab 200 mg administered via IV infusion Q3W."},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib 20 mg, 12 mg, or 8 mg (dependent on cancer type and body weight) administered via oral capsule QD"},{"intervention_type":"Drug","name":"Drug: 5-Fluorouracil","description":"5-FU 800 mg/m^2/day administered via continuous IV infusion on each of days 1 to 5 Q3W for up to 35 cycles"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Cisplatin 80 mg/m^2 administered via IV infusion Q3W up to 6 cycles"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Paclitaxel 90 mg/m^2 administered via IV infusion on days 1, 8, and 15 of every 28-day treatment cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 36 months","description":"ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented."},{"outcome_type":"primary","measure":"Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 36 months","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented."},{"outcome_type":"primary","measure":"ORR per RECIST 1.1 as Assessed by Investigator","time_frame":"Up to approximately 36 months","description":"ORR is defined as the percentage of participants who have a CR (Disappearance of all target lesions) or a PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by investigator based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 36 months","description":"OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"PFS per RECIST 1.1 as Assessed by Investigator","time_frame":"Up to approximately 36 months","description":"PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 36 months","description":"For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR will be presented."},{"outcome_type":"secondary","measure":"DOR per RECIST 1.1 as Assessed by Investigator","time_frame":"Up to approximately 36 months","description":"For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by investigator will be presented."},{"outcome_type":"secondary","measure":"Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30] Items 29 and 30)","time_frame":"Baseline and up to approximately 36 months","description":"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions \"How would you rate your overall health during the past week?\" and \"How would you rate your overall quality of life during the past week?\" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented."},{"outcome_type":"secondary","measure":"Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5)","time_frame":"Baseline and up to approximately 36 months","description":"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced One or More Adverse Events (AEs)","time_frame":"Up to approximately 36 months","description":"An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Intervention Due to an AE","time_frame":"Up to approximately 36 months","description":"An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study."}]}
{"nct_id":"NCT04975308","start_date":"2021-09-20","phase":"Phase 3","enrollment":500,"brief_title":"Study of LY3484356 Versus Hormone Therapy, in Participants With Estrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer","official_title":"EMBER-3: A Randomized, Open-Label, Phase 3 Study of LY3484356 vs Investigator's Choice of Endocrine Therapy, in Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With Endocrine Therapy","primary_completion_date":"2023-03-13","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-03-13","last_update":"2021-09-21","description":"The main purpose of this study is to measure how well LY3484356 works compared to hormone therapy in participants with breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). Participants must have breast cancer that is advanced or has spread to another part of the body. Study participation could last up to 5 years.","other_id":"18175","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        -  Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer\r\n\r\n          -  Have disease that has demonstrated progression on or after an aromatase inhibitor\r\n             alone or in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor.\r\n\r\n          -  Must be deemed appropriate for treatment with endocrine therapy\r\n\r\n          -  If female, have a postmenopausal status by natural or surgical means or by ovarian\r\n             function suppression\r\n\r\n          -  Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only\r\n             disease)\r\n\r\n          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale\r\n             (Oken et al. 1982)\r\n\r\n          -  Have adequate renal, hematologic, and hepatic organ function\r\n\r\n          -  Must be able to swallow capsules/tablets\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant\r\n             chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including\r\n             SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor\r\n\r\n          -  Have visceral crisis, lymphangitic spread within the lung, or any evidence of\r\n             leptomeningeal disease.\r\n\r\n          -  Have symptomatic or untreated brain metastasis.\r\n\r\n          -  Have serious preexisting medical conditions that, in the judgment of the investigator,\r\n             would preclude participation in this study\r\n\r\n          -  Known allergic reaction against any of the components of the study treatment\r\n      ","sponsor":"Eli Lilly and Company","sponsor_type":"Industry","conditions":"Neoplasm Metastasis|Breast Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: LY3484356","description":"Administered orally."},{"intervention_type":"Drug","name":"Drug: Exemestane","description":"Administered orally."},{"intervention_type":"Drug","name":"Drug: Fulvestrant","description":"Administered IM."}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS)","time_frame":"Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years)","description":"PFS by investigator assessment"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Randomization until death from any cause (estimated as up to 5 years)","description":"OS"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)","time_frame":"Randomization until measured progressive disease (estimated as up to 1 year)","description":"ORR"},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years)","description":"DoR"},{"outcome_type":"secondary","measure":"Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for Greater than or Equal to (≥) 24 Weeks","time_frame":"Randomization until measured progressive disease (estimated as up to 1 year)","description":"CBR"},{"outcome_type":"secondary","measure":"PFS by Estrogen Receptor 1 Gene (ESR1) Mutation Status in Plasma","time_frame":"Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years)","description":"Investigator-assessed PFS by ESR1 mutation status in plasma"},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"Randomization to the date of first documented progression of disease or death from any cause(estimated as up to 3 years)","description":"PFS by blinded independent review"},{"outcome_type":"secondary","measure":"Patient Reported Outcomes (PRO): Time to Worsening of \"Worst Pain\"","time_frame":"Screening through follow-up (estimated as up to 3 years)","description":"Measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single item, participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing \"no pain\" and 10 representing \"pain as bad as you can imagine.\""},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Steady State Plasma Concentrations of LY3484356","time_frame":"Cycle 2 to Cycle 4 (cycle = 28 days)","description":"PK: steady state plasma concentrations of LY3484356"}]}
{"nct_id":"NCT04950322","start_date":"2021-09-15","phase":"Phase 3","enrollment":920,"brief_title":"A Trial of SHR1701 Plus Chemotherapy in Patients With Gastric or Gastroesophageal Cancer","official_title":"A Randomized, Double-Blind, Multi-Center, Phase III Clinical Study of SHR-1701 Plus Chemotherapy Versus Placebo Plus Chemotherapy as Treatment in Patients With Previously Untreated, Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer","primary_completion_date":"2025-03-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-06-30","last_update":"2021-07-06","description":"This study is a randomized, Double-Blind, multi-center Phase III clinical study, aimed to evaluate the efficacy and safety of SHR1701 combined with chemotherapy in the treatment of Previously Untreated, Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer. For Part 1 studythe tolerability of SHR-1701 will be evaluated and determine the recommended dose for Part 2.For Part 2 study, all enrolled patients will be randomized to 2 groups and continuously treated until the end criteria of treatment was met.","other_id":"SHR-1701-III-307","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Pathologically confirmed diagnosis of locally advanced unresectable or metastatic\r\n             gastric or gastroesophageal junction (GEJ)adenocarcinoma.\r\n\r\n          2. HER2 overexpression or amplification negative.\r\n\r\n          3. Female or male, 18 years of age or above.\r\n\r\n          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.\r\n\r\n          5. Patients who are willing and able to provide the signed informed consent form, willing\r\n             and able to comply with all the scheduled visits, study treatment, laboratory tests,\r\n             and other study procedures.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Squamous cell carcinoma, undifferentiated carcinoma, or other histological types of\r\n             gastric cancer.\r\n\r\n          2. Presence of inadequately treated CNS metastases, or uncontrolled or symptomatic active\r\n             CNS metastases leptomeningeal disease, and/or rapid progression.\r\n\r\n          3. Presence of uncontrolled pleural effusion or ascites despite puncture drainage within\r\n             14 days prior to randomization.\r\n\r\n          4. More than 20% weight loss within 2 months prior to randomization.\r\n\r\n          5. Diagnosed with other malignant tumors within 5 years prior to enrollment.\r\n\r\n          6. Presence of any active, known or suspected autoimmune disease.\r\n\r\n          7. Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137\r\n             antibodies, anti-CTLA-4 antibodies, or other drugs/antibodies.\r\n\r\n          8. Severe, unhealed, or dehisced wounds and active ulcers or untreated fractures.\r\n      ","sponsor":"Suzhou Suncadia Biopharmaceuticals Co., Ltd.","sponsor_type":"Industry","conditions":"Gastric or Gastroesophageal Junction Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SHR-1701CAPOX/FOLFOX","description":"SHR-1701 with CAPOX/FOLFOX (CAPOX:Oxaliplatin,Capecitabine;FOLFOX:Oxaliplatin,Leucovorin,Fluorouracil\r\n)"},{"intervention_type":"Drug","name":"Drug: PlaceboCAPOX/FOLFOX","description":"Placebo with CAPOX/FOLFOX (CAPOX:Oxaliplatin,Capecitabine;FOLFOX:Oxaliplatin,Leucovorin,Fluorouracil\r\n)"}],"outcomes":[{"outcome_type":"secondary","measure":"DoR in part 1 study","time_frame":"up to 2 years","description":"Duration of response (DoR) as assessed by the investigator per RECIST 1.1"},{"outcome_type":"secondary","measure":"OS in part 1 study","time_frame":"up to 3 years","description":"Overall survival (OS)"},{"outcome_type":"primary","measure":"PFS in part 2 study assessed based on BICR","time_frame":"up to 2 years","description":"Progression-free survival(PFS) assessed based on BICR per RECIST 1.1"},{"outcome_type":"primary","measure":"OS in part 2 study","time_frame":"up to 3 years","description":"Overall survival (OS)"},{"outcome_type":"secondary","measure":"EORTC QLQ-C30 score","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"EORTC QLQ-STO22 score","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"EQ-5D-5L score","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"DoR in part 2 study","time_frame":"up to 2 years","description":"DoR in subjects with PD-L1 positive and all subjects assessed by BICR per RECIST 1.1"},{"outcome_type":"secondary","measure":"ORR in part 1 study","time_frame":"up to 2 years","description":"Objective response rate (ORR) as assessed by the investigator per RECIST 1.1"},{"outcome_type":"secondary","measure":"PFS in part 1 study","time_frame":"up to 2 years","description":"Progression free survival (PFS); as assessed by the investigator per RECIST 1.1"},{"outcome_type":"primary","measure":"AEs and SAEs in part 1 study","time_frame":"up to 2 years","description":"The number and proportion of subjects with dose limiting toxicity.The safety endpoints, including incidence and severity of adverse events (AEs) and serious adverse events (SAEs) ."},{"outcome_type":"secondary","measure":"ORR in part 2 study","time_frame":"up to 2 years","description":"ORR in subjects with PD-L1 positive and all subjects assessed by BICR per RECIST 1.1"},{"outcome_type":"secondary","measure":"PFS in part 2 study assessed by investigator","time_frame":"up to 2 years","description":"PFS in subjects with PD-L1 positive and all subjects assessed by investigator as per RECIST 1.1"},{"outcome_type":"secondary","measure":"AEs and SAEs in part 2 study","time_frame":"up to 2 years","description":"Safety endpoints, including incidence and severity of AEs and SAEs as per NCI-CTCAE v5.0 criteria."}]}
{"nct_id":"NCT04892342","start_date":"2021-09-14","phase":"Phase 1/Phase 2","enrollment":177,"brief_title":"Study of ESG401 in Adults With Solid Tumors","official_title":"An Open-Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of ESG401 in Subjects With Locally Advanced/Metastatic Solid Tumors","primary_completion_date":"2025-02-28","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-04-30","last_update":"2021-09-16","description":"The primary objective in Phase I is to evaluate the safety and tolerability of ESG401 as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of ESG401 administered in 21-day treatment cycles at a dose selected in Phase I. Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).","other_id":"ESG401-101","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Sequential Assignment","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Individuals able to understand and give written informed consent.\r\n\r\n          -  Subjects must have a histologically or cytologically confirmed advanced or metastatic\r\n             solid tumor(s) for which no effective standard therapy is available or tolerable.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Life expectancy 12 weeks.\r\n\r\n          -  Subject must have adequate organ function\r\n\r\n          -  Fertile men and women of childbearing potential must agree to use an effective method\r\n             of birth control from providing signed consent and for 180 days after last\r\n             investigational product administration. Women of childbearing potential include\r\n             pre-menopausal women and women within the first 2 years of the onset of menopause.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects receiving cancer therapy (chemotherapy or other systemic anti-cancer\r\n             therapies, immunotherapy, or radiation therapy) within 4 weeks before the first\r\n             investigational product administration..\r\n\r\n          -  Has not recovered from adverse events (e.g., returned to baseline or grade 0~1) due to\r\n             a previously administered agent.\r\n\r\n        Note: Subjects with Grade 2 alopecia or anemia are exceptions to this criterion and may\r\n        qualify for the study.\r\n\r\n          -  Had major surgery within 4 weeks before dosing, or will not have fully recovered from\r\n             surgery; or has surgery planned during the time the subject is expected to participate\r\n             in the study or within 4 weeks after the last dose of study drug administration.\r\n\r\n          -  Use of any investigational anti-cancer drug within 28 days before the first\r\n             investigational product administration.\r\n\r\n          -  New thromboembolic events, intestinal obstruction, gastrointestinal bleeding or\r\n             perforation within 6 months\r\n\r\n          -  Uncontrolled systemic bacterial, viral or fungal infections\r\n\r\n          -  Subjects with symptomatic or untreated CNS metastases, or those requiring ongoing\r\n             treatment for CNS metastases.\r\n\r\n          -  Primary CNS malignancy; Or a second primary tumor other than the confirmed solid tumor\r\n             within the previous 3 years\r\n\r\n          -  Evidence of serious or uncontrolled systemic disease (e.g., unstable or decompensated\r\n             respiratory disease, liver disease or kidney disease)\r\n\r\n          -  Patients with gastrointestinal diseases (such as chronic gastritis, chronic enteritis\r\n             or gastric ulcers), or with a previous history of severe or chronic diarrhea\r\n\r\n          -  History of chronic skin disease and present skin disease (e.g. bullous dermatitis,\r\n             acnelike rash, skin ulcer, etc.)\r\n\r\n          -  Subjects with clinically significant cardiovascular disease as defined by the\r\n             following:\r\n\r\n               -  Baseline left ventricular ejection fraction (LVEF)  50% measured by\r\n                  Echocardiogram (ECHO) or Multi-gated acquisition (MUGA)\r\n\r\n               -  Heart failure New York Heart Association (NYHA) Class II or above\r\n\r\n               -  Uncontrolled hypertension (BP  150/95 mmHg despite optimal therapy)\r\n\r\n               -  Prior or current cardiomyopathy\r\n\r\n               -  Atrial fibrillation with heart rate > 100 bpm\r\n\r\n               -  Unstable ischaemic heart disease (myocardial infarction (MI) within 6 months\r\n                  prior to starting treatment, or angina requiring use of nitrates more than once\r\n                  weekly)\r\n\r\n               -  QTc interval >/= 450 msecs for male or >/= 470 msecs for female (Fridericia's\r\n                  formula: QTc=QT/RR0.33).\r\n\r\n          -  Human Immunodeficiency Virus (HIV) infection.\r\n\r\n          -  Subjects who are Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody\r\n             (HBcAb) positive or Hepatitis C virus (HCV) antibody positive at screening must not be\r\n             enrolled until further definite testing with Hepatitis B virus (HBV) DNA titres and\r\n             HCV RNA tests can conclusively rule out presence of active infection (HBV DNA  1000\r\n             cps/mL or 200 IU/mL) requiring antiviral therapy with Hepatitis B and C, respectively\r\n\r\n          -  Known immediate or delayed hypersensitivity reaction to irinotecan or other\r\n             camptocampin derivatives such as topotecan or to have had grade 3 gastrointestinal\r\n             reactions associated with irinotecan, or allergies, or to any investigational drug or\r\n             excipient ingredient\r\n\r\n          -  Concurrent condition that in the investigator's opinion would jeopardize compliance\r\n             with the protocol.\r\n\r\n          -  Unwillingness or inability to follow the procedures outlined in the protocol.\r\n      ","sponsor":"Shanghai Escugen Biotechnology Co., Ltd","sponsor_type":"Industry","conditions":"Neoplasms, Breast|Neoplasms, Lung|Neoplasms,Colorectal|Neoplasms, Bladder|Neoplasm of Stomach|Neoplasms,Ovarian","interventions":[{"intervention_type":"Drug","name":"Drug: ESG401","description":"Administered via intravenous (IV) infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events","time_frame":"First dose date up to last dose plus 30 days","description":"Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0. An AE that met one or more of the following outcomes was classified as serious:\r\nFatal Life-threatening Disabling/incapacitating Results in hospitalization or prolongs a hospital stay A congenital abnormality Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above"},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) by Independent Central Review (ICR)","time_frame":"Up to 49 months","description":"ORR is defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR will be assessed for the TNBC Target Population in phase 2 only."},{"outcome_type":"secondary","measure":"Cmax","time_frame":"Up to 49 months","description":"Maximum observed plasma concentration"},{"outcome_type":"secondary","measure":"AUC0-inf","time_frame":"Up to 49 months","description":"Area under the serum concentration time curve from time 0 extrapolated to infinity"},{"outcome_type":"secondary","measure":"Objective Response Rate by Local Assessment","time_frame":"Up to 49 months","description":"ORR is defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by local assessment will be assessed for the Target Population both in phase 1 and phase 2."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) by Local Assessment","time_frame":"Up to 49 months","description":"Progression-free survival (PFS) is defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall Survival by Local Assessment","time_frame":"Up to 49 months","description":"Overall survival is defined as the time from the date of the first dose start date to the date of death due to any cause."},{"outcome_type":"secondary","measure":"ADA","time_frame":"Up to 49 months","description":"Incidence of anti-drug antibodies"}]}
{"nct_id":"NCT04895410","start_date":"2021-09-13","phase":"Phase 1","enrollment":170,"brief_title":"Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Lemzoparlimab (TJ011133) With or Without Oral/IV Dexamethasone and in Combination With Oral/IV/Subcutaneous Anti-Myeloma Regimens in Adult Participants With Multiple Myeloma","official_title":"A Phase 1b, Dose Escalation and Expansion Study of Lemzoparlimab (TJ011133) With or Without Dexamethasone and in Combination With Anti-Myeloma Regimens for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma","primary_completion_date":"2025-07-24","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-08-10","last_update":"2021-09-20","description":"Multiple myeloma (MM) accounts for more than 10% of all blood cancers and 1% of all cancers. The purpose of this study is to assess how safe lemzoparlimab (TJ01133) is and how lemzoparlimab (TJ01133) moves through the body of adult participants with MM when given with or without dexamethasone, and in combination with other anti-myeloma regimens. Adverse events and change in disease activity will be assessed. Lemzoparlimab (TJ01133) is an investigational drug being developed for the treatment of relapsed/refractory (R/R) MM. Study doctors put the participants in groups called treatment arms. Two different dose levels of lemzoparlimab (TJ011133) will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of lemzoparlimab (TJ011133), followed by a dose expansion phase to confirm the dose. Approximately 163 adult participants with R/R MM will be enrolled in the study in approximately 60 sites worldwide. In the Dose Escalation arms, participants will receive intravenous (IV) lemzoparlimab (TJ011133) with or without dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or subcutaneous (SC) daratumumab in 28-day cycles. In the Dose Expansion arms, participants will receive lemzoparlimab (TJ011133) (IV) alone or with dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or daratumumab (SC) in 28-day cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests and side effects.","other_id":"M20-917","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Diagnosis of relapsed/refractory (R/R) multiple myeloma (MM) with documented evidence\r\n             of progression during or after the participant's last treatment regimen based on the\r\n             investigator's determination of the International Myeloma Working Group (IMWG)\r\n             criteria.\r\n\r\n               -  Relapsed defined as previously treated myeloma that progresses and requires\r\n                  initiation of salvage therapy, but does not meet criteria for refractory myeloma.\r\n\r\n               -  Refractory defined as disease that is nonresponsive (failure to achieve minimal\r\n                  response or development of progressive disease) while on primary or salvage\r\n                  therapy, or progresses within 60 days of last therapy.\r\n\r\n          -  Measurable disease within 28 days prior to enrollment.\r\n\r\n          -  Arm A - Lemzoparlimab (TJ011133) with or without Dexamethasone\r\n\r\n               -  For Both Escalation and Expansion Phase, participant must have refractory to 3\r\n                  prior lines of treatment including standard of care (SOC).\r\n\r\n          -  Arm B - Lemzoparlimab (TJ011133) + Pomalidomide-Dexamethasone\r\n\r\n               -  For Escalation Phase - Participant must have received at least 2 prior lines of\r\n                  therapy, including lenalidomide and a Proteasome inhibitor (PI).\r\n\r\n               -  For Expansion Phase - Participant must have received at least 1 prior line of\r\n                  therapy, including lenalidomide and a Proteasome inhibitor (PI).\r\n\r\n          -  Arm C - Lemzoparlimab (TJ011133) + Carfilzomib-Dexamethasone\r\n\r\n               -  For Both Escalation and Expansion Phase - Participant must have received at least\r\n                  1 prior line of therapy.\r\n\r\n          -  Arm D - Lemzoparlimab (TJ011133) + Daratumumab-Dexamethasone\r\n\r\n               -  For Escalation Phase: Participant must have received at least 3 prior lines of\r\n                  therapy including a PI and an Immunomodulatory imide drug (IMiD).\r\n\r\n               -  For Expansion Phase: Participant must have received at least 1 prior line of\r\n                  therapy including a PI and an IMiD.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Arm B - Lemzoparlimab (TJ011133) + Pomalidomide-Dexamethasone\r\n\r\n               -  For Both Escalation and Expansion Phase participant must have had no prior\r\n                  treatment with pomalidomide.\r\n\r\n          -  Arm C - Lemzoparlimab (TJ011133) + Carfilzomib-Dexamethasone\r\n\r\n               -  For Both Escalation and Expansion Phase - prior treatment with carfilzomib.\r\n\r\n          -  Arm D - Lemzoparlimab (TJ011133) + Daratumumab-Dexamethasone\r\n\r\n               -  For Both Escalation and Expansion Phase - prior treatment with daratumumab or\r\n                  other anti-CD38 therapy.\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"Multiple Myeloma","interventions":[{"intervention_type":"Biological","name":"Biological: Lemzoparlimab","description":"Intravenous (IV) infusion"},{"intervention_type":"Drug","name":"Drug: Dexamethasone","description":"Oral tablet or IV infusion/injection"},{"intervention_type":"Drug","name":"Drug: Carfilzomib","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Pomalidomide","description":"Oral capsule"},{"intervention_type":"Biological","name":"Biological: Daratumumab","description":"Subcutaneous (SC) injection"}],"outcomes":[{"outcome_type":"primary","measure":"Dose Limiting Toxicities (DLTs) of Lemzoparlimab (TJ011133) With or Without Dexamethasone and in Combination With Anti-myeloma Regimens in Participants With Relapsed/Refractory (R/R) Multiple Myeloma (MM)","time_frame":"Up to 28 days after study drug administration","description":"DLT events as described in the protocol will be assessed."},{"outcome_type":"secondary","measure":"Percentage of Participants Achieving Best Overall Response of Documented Partial Response (PR) or Better","time_frame":"Up to approximately 2 years","description":"Best overall response is defined as achieving documented PR or better at two consecutive disease assessments during the study, according to International Myeloma Working Group (IMWG) 2016 criteria."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"Up to approximately 2 years","description":"PFS is defined as the time from the first dose of study drug to the first documented progressive disease (PD) or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to approximately 2 years","description":"DOR is defined as the time from first documented response (PR or better) to the first documented PD or death due to MM, whichever occurs first."},{"outcome_type":"secondary","measure":"Time to Progression (TTP)","time_frame":"Up to approximately 2 years","description":"TTP is defined as the time from the first dose of study drug to the first documented PD or death due to MM, whichever occurs first."}]}
{"nct_id":"NCT05005403","start_date":"2021-09-11","phase":"Phase 1","enrollment":136,"brief_title":"Study to Assess Adverse Events and Pharmacokinetics in Adult Participants With Non-Small Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC) and Other Solid Tumors, Receiving Intravenous (IV) Infusion of ABBV-514 Alone or in Combination With Pembrolizumab or Budigalimab","official_title":"A Global First-in-Human Study in NSCLC, HNSCC and Solid Tumors With ABBV-514 as a Single Agent and in Combination With Pembrolizumab or Budigalimab","primary_completion_date":"2026-05-02","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-05-02","last_update":"2021-08-13","description":"Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of ABBV-514 as a monotherapy and in combination with Pembrolizumab or Budigalimab. Budigalimab and ABBV-514 are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Pembrolizumab is a drug approved for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The Recommended Phase 2 dose (RP2D) of ABBV-514 will be explored. Each treatment arm receives a different doses of ABBV-514 in monotherapy and in combination with Pembrolizumab or Budigalimab. Approximately 136 adult participants will be enrolled in the study across approximately 80 sites worldwide. Participants will receive ABBV-514 as a monotherapy or in combination with Pembrolizumab or Budigalimab as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.","other_id":"M21-410","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Dose-escalation cohorts only:\r\n\r\n             -- Must have an advanced solid tumor who are considered refractory to or intolerant of\r\n             all existing therapies known to provide a clinical benefit for their condition.\r\n\r\n          -  Relapsed Non-Small Cell Lung Cancer (NSCLC) Head and Neck Squamous Cell Carcinoma\r\n             (HNSCC) dose-expansion cohorts only:\r\n\r\n               -  Must have histologically or cytologically confirmed advanced or metastatic NSCLC\r\n                  or HNSCC that has been treated with platinum-based chemotherapy and a programmed\r\n                  cell death (PD)-1 or PD ligand 1 (PD-L1) targeting agent (separately or in\r\n                  combination therapy).\r\n\r\n               -  Must have failed (or refused) treatment with available therapies known to be\r\n                  active for treatment of their disease.\r\n\r\n          -  Participants enrolled in dose escalation must have disease that is evaluable or\r\n             measurable per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).\r\n\r\n          -  Participants enrolled in dose expansion must have measurable disease per RECIST,\r\n             version 1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of  1.\r\n\r\n          -  Laboratory values meeting the criteria outlined in the protocol.\r\n\r\n        Exclusion Criteria:\r\n\r\n        - Relapsed Non-Small Cell Lung Cancer (NSCLC) Head and Neck Squamous Cell Carcinoma (HNSCC)\r\n        dose-expansion cohorts only:\r\n\r\n        -- Non-Small Cell Lung Cancer (NSCLC) participants with known EGFR mutations or ALK gene\r\n        rearrangements are ineligible.\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer|Head and Neck Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: ABBV-514","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"IV Infusion"},{"intervention_type":"Drug","name":"Drug: Budigalimab","description":"IV Infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants with Adverse Events (AE)","time_frame":"Up to 2 Years","description":"An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment."},{"outcome_type":"primary","measure":"Maximum Observed Serum Concentration (Cmax) of ABBV-514","time_frame":"Up to 2 Years","description":"Maximum Observed Serum Concentration (Cmax) of of ABBV-154."},{"outcome_type":"primary","measure":"Time to Maximum Observed Serum Concentration (Tmax) of ABBV-514","time_frame":"Up to 2 Years","description":"Time to maximum Observed Serum Concentration (Tmax) of of ABBV-154."},{"outcome_type":"primary","measure":"Terminal Elimination Half-Life (t1/2) of ABBV-514","time_frame":"Up to 2 Years","description":"Terminal elimination half-life (t1/2) of ABBV-514."},{"outcome_type":"primary","measure":"Area Under the Serum Concentration Versus Time Curve (AUC) of ABBV-514","time_frame":"Up to 2 Years","description":"Area under the serum concentration versus time curve (AUC) of ABBV-514."},{"outcome_type":"primary","measure":"Antidrug Antibody (ADA)","time_frame":"Up to 2 Years","description":"Incidence and concentration of anti-drug antibodies."},{"outcome_type":"primary","measure":"Neutralizing Antidrug Antibody (ADA)","time_frame":"Up to 2 Years","description":"Incidence and concentration of neutralizing anti-drug antibodies."}]}
{"nct_id":"NCT05005234","start_date":"2021-09-10","phase":"Phase 1/Phase 2","enrollment":128,"brief_title":"A Study of GFH925 in Patients With Advanced Solid Tumors With KRAS G12C Mutations","official_title":"An Open-label, Multi-center Phase I/II Clinical Study Evaluating the Safety/Tolerability, Pharmacokinetics, and Effectiveness of GFH925 in Patients With Advanced Solid Tumors With KRAS G12C Mutations","primary_completion_date":"2024-01-10","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-10","last_update":"2021-08-13","description":"Phase I: To evaluate the safety and tolerability of GFH925 in subjects with KRAS G12C mutant advanced solid tumors and estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D).Phase II: To evaluate the efficacy of GFH925 in subjects with KRAS G12C mutant advanced non-small cell lung cancer (NSCLC).","other_id":"GFH925X1101","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Men or women 18 years old\r\n\r\n          -  Pathologically diagnosed, previously treated, advanced tumor with KRAS p.G12C mutation\r\n\r\n          -  Adequate organ function\r\n\r\n          -  Measurable disease per RECIST 1.1 criteria.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Significant concomitant diseases\r\n\r\n          -  Active brain metastases\r\n\r\n          -  Previous treatment with KRAS G12C inhibitor.\r\n      ","sponsor":"Zhejiang Genfleet Therapeutics Co., Ltd.","sponsor_type":"Industry","conditions":"KRAS G12C","interventions":[{"intervention_type":"Drug","name":"Drug: GFH925","description":"Administered as an oral tablet formulation"}],"outcomes":[{"outcome_type":"primary","measure":"Number of subjects with dose-limiting toxicities (DLTs)","time_frame":"Baseline to 24 Months"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) as assessed by RECIST 1.1 criteria","time_frame":"Baseline to 24 Months"}]}
{"nct_id":"NCT04816214","start_date":"2021-09-10","phase":"Phase 3","enrollment":245,"brief_title":"Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy","official_title":"A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating Mutations Who Have Progressed on Prior 1st / 2nd Generation EGFR-TKI or Osimertinib Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)","primary_completion_date":"2025-01-16","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-03-30","last_update":"2021-08-27","description":"This phase III study is designed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who progressed following 1st/2nd generation EGFR tyrosine kinase inhibitors (TKIs) or osimertinib. The randomized part will be preceded by a safety run-in part in which the recommended dose of the combination of capmatinib and osimertinib will be confirmed.","other_id":"CINC280L12301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known\r\n             to be associated with EGFR TKI sensitivity, T790M negative and MET gene amplification\r\n\r\n          -  Stage IIIB/IIIC NSCLC\r\n\r\n          -  Patients must have failed maximum one prior line of therapy (either to 1st/2nd\r\n             generation EGFR TKIs or osimertinib) for advanced/metastatic disease (stage IIIB/IIIC\r\n             and must be candidates for platinum (cisplatin or carboplatin) - pemetrexed doublet\r\n             based chemotherapy\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1\r\n\r\n          -  Participants must have recovered from all toxicities related to prior systemic therapy\r\n             to grade  1 Common Terminology Criteria Adverse Event 5.0 (CTCAE v 5.0)\r\n\r\n          -  At least one measurable lesion as defined by RECIST 1.1\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Prior treatment with any MET inhibitor or HGF-targeting therapy\r\n\r\n          -  Participants with symptomatic central nervous system (CNS) metastases who are\r\n             neurologically unstable or have required increasing doses of steroids within the 2\r\n             weeks prior to study entry to manage CNS symptoms\r\n\r\n          -  Carcinomatous meningitis\r\n\r\n          -  Presence or history of a malignant disease other than NSCLC that has been diagnosed\r\n             and/or required therapy within the past 3 years\r\n\r\n          -  Presence or history of interstitial lung disease or interstitial pneumonitis,\r\n             including clinically significant radiation pneumonitis\r\n\r\n          -  Long QT syndrome, family history of idiopathic sudden death or congenital long QT\r\n             syndrome\r\n\r\n          -  Clinically significant, uncontrolled heart diseases\r\n\r\n        Other protocol-defined inclusion/exclusion criteria may apply.\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Carcinoma, Non-Small-Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: pemetrexed","description":"concentrate for solution for intravenous use"},{"intervention_type":"Drug","name":"Drug: cisplatin","description":"concentrate for solution for intravenous use"},{"intervention_type":"Drug","name":"Drug: carboplatin","description":"concentrate for solution for intravenous use"},{"intervention_type":"Drug","name":"Drug: osimertinib","description":"tablet for oral use"},{"intervention_type":"Drug","name":"Drug: capmatinib","description":"film-coated tablet for oral use"}],"outcomes":[{"outcome_type":"primary","measure":"Run-in part: Incidence of dose limiting toxicities (DLTs)","time_frame":"3 weeks","description":"Incidence of Dose Limiting Toxicities (DLT) during the first 21 days (3 weeks) of treatment for each dose level associated with administration of capmatinib in combination with osimertinib"},{"outcome_type":"primary","measure":"Randomized part: Progression free survival (PFS)","time_frame":"37 months","description":"Progression free survival (PFS) per Blinded Independent Review Committee (BIRC) according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1)"},{"outcome_type":"secondary","measure":"Run-in part: Percentage of participants with dose adjustments (reductions, interruptions or permanent discontinuation)","time_frame":"6 months","description":"To define the percentage of participants with dose adjustments (reductions, interruption, or permanent discontinuation) and the reasons by treatment arm"},{"outcome_type":"secondary","measure":"Run-in part: Dose intensity of each study drug","time_frame":"6 months","description":"Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure"},{"outcome_type":"secondary","measure":"Run-in part: Median Duration of exposure to each study drug","time_frame":"6 months","description":"Median duration of exposure to capmatinib and osimertinib where duration of exposure is defined as the time between the first and last dose of treatment"},{"outcome_type":"secondary","measure":"Run-in part: Maximum plasma concentration (Cmax) of capmatinib","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days)","description":"The Cmax values are based on the plasma concentration-time profile of capmatinib. To characterize the pharmacokinetics of capmatinib"},{"outcome_type":"secondary","measure":"Run-in part: Maximum plasma concentration (Cmax) of osimertinib and its metabolites","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days), and also 24 hours post-dose on Cycle 1 Day 1.","description":"The Cmax values are based on the plasma concentration-time profile of osimertinib and its metabolites. To characterize the pharmacokinetics of osimertinib and its metabolites in combination setting"},{"outcome_type":"secondary","measure":"Run-in part: Time to maximum plasma concentration (Tmax) of capmatinib","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days)","description":"The Tmax values are based on the plasma concentration-time profile of capmatinib. To characterize the pharmacokinetics of capmatinib"},{"outcome_type":"secondary","measure":"Run-in part: Time to maximum plasma concentration (Tmax) of osimertinib and its metabolites","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days), and also 24 hours post-dose on Cycle 1 Day 1.","description":"The Tmax values are based on the plasma concentration-time profile of osimertinib and its metabolites. To characterize the pharmacokinetics of osimertinib and its metabolites in combination setting"},{"outcome_type":"secondary","measure":"Run-in part: Area Under the Curve (AUC) of capmatinib","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days)","description":"The AUC values are based on the plasma concentration-time profile of capmatinib. To characterize the pharmacokinetics of capmatinib"},{"outcome_type":"secondary","measure":"Run-in part: Area Under the Curve (AUC) of osimertinib and its metabolites","time_frame":"pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Cycle 1 Day 1 and Day 15 (one cycle is 21 days), and also 24 hours post-dose on Cycle 1 Day 1.","description":"The AUC values are based on the plasma concentration-time profile of osimertinib and its metabolites. To characterize the pharmacokinetics of osimertinib and its metabolites"},{"outcome_type":"secondary","measure":"Run-in part: Duration of response (DOR)","time_frame":"6 months","description":"Duration of response is defined as the time from first documented response of complete response (CR) or partial response (PR) to date of first documented progression or death as per investigator judgment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Run-in part: Overall Response Rate (ORR)","time_frame":"6 months","description":"ORR is defined as the proportion of subjects with confirmed best overall response of CR or PR, as per investigator judgment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Run-in part only: Time to Response (TTR)","time_frame":"6 months","description":"Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR as per investigator judgment according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Run-in part: Disease control rate (DCR)","time_frame":"6 months","description":"Disease control rate is defined as the proportion of subjects with CR or PR or subjects with stable disease (SD) as per investigator judgment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Run-in part: Progression-Free Survival (PFS)","time_frame":"6 months","description":"Progression-free survival is defined as the time from randomization to the date of the first documented radiological progression as per investigator judgment according to RECIST 1.1 response criteria or death due to any cause"},{"outcome_type":"secondary","measure":"Randomized part: Overall Response Rate (ORR)","time_frame":"37 months","description":"ORR is defined as the proportion of subjects with confirmed best overall response of CR or PR, as per BIRC according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Randomized part: plasma concentration of capmatinib","time_frame":"Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (one cycle is 21 days)","description":"Plasma concentration to characterize the pharmacokinetics of capmatinib"},{"outcome_type":"secondary","measure":"Randomized part: plasma concentration of osimertinib and its metabolites","time_frame":"Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (one cycle is 21 days)","description":"Plasma concentration to characterize the pharmacokinetics of osimertinib and its metabolites in combination setting"},{"outcome_type":"secondary","measure":"Randomized part: overall intracranial response rate (OIRR)","time_frame":"37 months","description":"OIRR is defined as the proportion of participants with a confirmed best overall intracranial response (BOIR) of CR or PR as per BIRC according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria"},{"outcome_type":"secondary","measure":"Randomized part: Duration of response (DOR)","time_frame":"37 months","description":"Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death as per BIRC according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Randomized part: Time to Response (TTR)","time_frame":"37 months","description":"Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR as per BIRC according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Randomized part: Disease control rate (DCR)","time_frame":"37 months","description":"Disease control rate is defined as the proportion of patients with CR or PR or subjects with SD as per BIRC according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Randomized part: Progression-Free Survival after next line of treatment (PFS2)","time_frame":"37 months","description":"PFS2 is defined as the documented radiological progression after next-line of treatment as per investigator judgment according to RECIST 1.1 response criteria or death due to any cause"},{"outcome_type":"secondary","measure":"Randomized part: PFS for participants with MET amplification as measured in circulating tumor DNA (ctDNA)","time_frame":"37 months","description":"Progression-free survival is defined as the time from randomization to the date of the first documented radiological progression as per BIRC according to RECIST 1.1 response criteria or death due to any cause"},{"outcome_type":"secondary","measure":"Randomized part: ORR for participants with MET amplification as measured in ctDNA","time_frame":"37 months","description":"ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per BIRC by RECIST 1.1"},{"outcome_type":"secondary","measure":"Randomized part: Overall Survival (OS)","time_frame":"37 months","description":"OS is defined as the time from date of randomization/start of treatment to date of death due to any cause"},{"outcome_type":"secondary","measure":"Randomized part: change from baseline in the EORTC QLQ-C30 score","time_frame":"Baseline, 37 months","description":"The European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (EORTC QLQ-C30) is a questionnaire developed to assess the quality of life of cancer patients. It contains 30 items and is composed of both multi-item scales and single-item measures based on the patients experience over the past week. These include five scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life scale (QoL) scale. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high /healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology/problems."},{"outcome_type":"secondary","measure":"Randomized part: change from baseline in the EORTC QLQ-LC13 score","time_frame":"Baseline, 37 months","description":"The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from \"not at all\" to \"very much\". Pain score is based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms."},{"outcome_type":"secondary","measure":"Randomized part: change from baseline in the EQ-5D-5L score","time_frame":"Baseline, 37 months","description":"The EuroQoL-5 Dimension-5 Level (EQ-5D-5L) is a standardized measure of health status developed by the EuroQol (EQ) Group in order to provide a simple, generic measure of health for clinical and economic appraisal The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The participant is asked to indicate his/her health state by ticking in the box against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number expressing the level selected for that dimension. The EQ VAS records the participant's self-rated health on a 20 cm vertical VAS with endpoints labeled 'the best health you can imagine' at the top and 'the worst health you can imagine' at the bottom."},{"outcome_type":"secondary","measure":"Randomized part: change from baseline in the NCCN FACT-Brain Symptom Index","time_frame":"Baseline, 37 months","description":"The National Comprehensive Cancer Network (NCCN) Functional Assessment of Cancer Therapy (FACT)-Brain Symptom Index version 2.0 (FBrSI) will be used to explore changes in symptoms associated with potential BM in this study. The FBrSI was adapted from the previously developed FACT-Brain module. The symptoms module contains 12 items with a recall period of the past 7 days. The participant responds to 12 statements and indicates to what extent it applies to them on a 5-point Likert response scale from \"not at all\" to \"very much.\""},{"outcome_type":"secondary","measure":"Randomized part: Time to symptom deterioration for EORTC QLQ-C30 questionnaire","time_frame":"37 months","description":"Time to symptom deterioration from baseline category to one more severe category of the EORTC QLQ-C30 questionnaire"},{"outcome_type":"secondary","measure":"Randomized part: Time to symptom deterioration for EORTC QLQ-LC13 questionnaire","time_frame":"37 months","description":"Time to symptom deterioration from baseline category to one more severe category of the EORTC QLQ-LC13 questionnaire"},{"outcome_type":"secondary","measure":"Randomized part: Time to symptom deterioration for EQ-5D-5L questionnaire","time_frame":"37 months","description":"Time to symptom deterioration from baseline category to one more severe category of the EQ-5D-5L questionnaire"},{"outcome_type":"secondary","measure":"Randomized part: Duration of intracranial response (DOIR)","time_frame":"37 months","description":"Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death as per BIRC according to RANO-BM criteria"},{"outcome_type":"secondary","measure":"Randomized part: Time to intracranial response (TTIR)","time_frame":"37 months","description":"TTIR is defined as the time from the date of randomization/start of the treatment to the date of the first documented intracranial response of either CR or PR as per BIRC according to RANO-BM criteria"},{"outcome_type":"secondary","measure":"Randomized part: Intracranial Disease control rate (IDCR)","time_frame":"37 months","description":"Intracranial Disease control rate is defined as the proportion of patients with CR or PR or subjects with SD as per BIRC according to RANO-BM criteria"}]}
{"nct_id":"NCT04797390","start_date":"2021-09-10","phase":"N/A","enrollment":250,"brief_title":"A Study Evaluating an Advanced Pneumatic Compression Device Versus Usual Care for Treatment of Head and Neck Lymphedema","official_title":"A Randomized Trial of an Advanced Pneumatic Compression Device vs. Usual Care for Head and Neck Lymphedema","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-31","last_update":"2021-09-21","description":"To compare the effectiveness of an APCD to Usual Care in the management of lymphedema and fibrosis (LEF) in head and neck cancer (HNC) survivors.","other_id":"8030","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Single","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Age  18 years\r\n\r\n          2. Pathologically confirmed cancer of the HNC (larynx, pharynx, oral cavity, paranasal\r\n             sinuses, major salivary glands, and HNC of unknown primary)\r\n\r\n          3. Completed curative intent cancer therapy with no evidence of active cancer at time of\r\n             study enrollment\r\n\r\n          4. A diagnosis of either internal or external head and neck lymphedema\r\n\r\n          5. At least one core lymphedema associated symptom of  4 out of 10 at the time of study\r\n             screening\r\n\r\n          6. Must be able and willing to participate in all aspects of the study and provide\r\n             informed consent prior to study participation\r\n\r\n          7. Must be able to speak and understand English\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Previous APCD or Usual Care treatment for HNC LEF\r\n\r\n          2. Acute facial infection (e.g., facial or parotid gland abscess)\r\n\r\n          3. Known carotid sinus hypersensitivity syndrome\r\n\r\n          4. Symptomatic carotid artery disease, as manifested by a recent transient ischemic\r\n             attack (within 30 days), ischemic stroke, or amaurosis fugax (monocular visual\r\n             ischemic symptoms or blindness)\r\n\r\n          5. Internal jugular venous thrombosis (within 3 months)\r\n\r\n          6. Patient is pregnant or trying to become pregnant\r\n      ","sponsor":"Tactile Medical","sponsor_type":"Industry","conditions":"Lymphedema; Surgical|Lymphedema Due to Radiation|Lymphedema, Secondary|Lymphedema of Face|Lymphedema","interventions":[{"intervention_type":"Device","name":"Device: Advanced Pneumatic Compression Device (APCD)","description":"Once daily treatment with Flexitouch Plus."},{"intervention_type":"Other","name":"Other: Usual Care","description":"Usual care consists of a two-phase CDT. Phase 1 includes consultation with a lymphedema therapist, patient education, MLD, compression garments or bandages, skin care techniques, and a program of exercises and postural recommendations. Phase 2 consists of ongoing self-care, where patients conduct a life-long program of disease management that mimics the program in phase 1."}],"outcomes":[{"outcome_type":"primary","measure":"Reduction in Swelling/Inflammation - Endoscopy","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"The change in percent of sites with visible swelling and inflammation as assessed via endoscopy (using Modified Patterson Scale). The range for each anatomical structure includes 1-4: Normal, Mild, Moderate, and Severe. A lower score means a better outcome. A greater negative value indicates a greater reduction in swelling. Total score range: 0-100%"},{"outcome_type":"primary","measure":"Reduction in Swelling/Imaging - CT","time_frame":"Changes between Baseline, 2 months, 6 months","description":"The changes in fat stranding, epiglottic thickness, and prevertebral soft tissue (PVST) using the CT Lymphedema and Fibrosis Assessment Tool (CT-LEFAT). The range for fat stranding includes 0-2: Normal, Mild Changes, Advanced Changes. A lower score means a better outcome. Epiglottis and PVST are measured in mm. A lower measurement means a better outcome."},{"outcome_type":"primary","measure":"Reduction in Swelling/Inflammation - Grading of External Lymphedema","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"The presence of swelling and inflammation as assessed through grading of external lymphedema via the Head and Neck Lymphedema and Fibrosis Assessment criteria (HNLEF). A total of 9 sites are evaluated for the presence of lymphedema and graded from 1 (mild) to 3 (severe) at each site. The number of sites ranged from 0-9 with a total severity score ranging from 0-27. A lower score indicates a better outcome. A greater negative value indicates a greater reduction in swelling."},{"outcome_type":"primary","measure":"Reduction in Swelling/Inflammation - Digital Photography","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"The presence of swelling and inflammation are assessed by digital photography. A lower value means a better outcome. A greater negative value indicates a greater reduction in swelling. Three views are scored each with 30 grids. The percentage of views with visible swelling was determined. The score ranges from 0-100%."},{"outcome_type":"primary","measure":"Symptom Burden - Lymphedema Symptom Intensity and Distress Survey","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Lymphedema Symptom Intensity and Distress Survey-Head and Neck (LSIDS-HN) assesses the measurement characteristics of a symptom burden for participants with head and neck lymphedema. Each symptom is rated on intensity and distress using a 5-point scale. A maximum response for any symptom within a given cluster will be used for the analysis. The total score ranged from 0-10. The values represent a change from baseline. A lower score means a better outcome."},{"outcome_type":"primary","measure":"Symptom Burden and Functional Impairment - Vanderbilt Head and Neck Symptom Survey","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Vanderbilt Head and Neck Symptom Survey plus General Symptom Survey (VHNSS plus GSS) assesses symptom burden and functional impairment. Values represent a median score change from baseline. Score range: 0-10. A lower score indicates a better outcome. A more negative value indicates a greater change from baseline."},{"outcome_type":"primary","measure":"Quality of Life - Linear Analog Self-Assessment","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Quality of life is assessed using the Linear Analog Self-Assessment. The total score for the assessment ranges from 0-50. Each category represents a change in score from the baseline visit which ranged from positive 4 to negative 4. A positive change indicates an improvement."},{"outcome_type":"primary","measure":"Work and Activity - Work Productivity and Activity Impairment Questionnaire","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Work Productivity and Activity Impairment Questionnaire (WPAIQ) PRO assessment asks questions about work and activity impairment due to lymphedema and other health problems. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. Total score range: 0-100%"},{"outcome_type":"primary","measure":"Perceived self-management capacity - Perceived Medical Condition Self-Management Scale (PMCSMS)","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"The 8-item Perceived Medical Condition Self-Management Scale (PMCSMS) is intended to measure patients' belief that they are capable of carrying out the self-management behaviors required by their medical condition. The scale is composed of four positively worded items and four negatively worded items, each rated on a five-point Likert scale (1=Strongly Disagree to 5=Strongly Agree). Negatively worded items are reversed scored, yielding a total score ranging from 8 to 40, with a higher score indicating stronger belief of perceived self-management competence."},{"outcome_type":"primary","measure":"Body image - Body Image Quality of Life Inventory (BIQLI)","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Body Image Quality Life Inventory (BIQLI) assesses participants' body image using 7 point scale ranging from -3 (very negative) to +3 (very positive). Score range: -57 to 57. A higher score indicates a better outcome."},{"outcome_type":"primary","measure":"Diet modifications - Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24)","time_frame":"Changes between Baseline, 2 months, 4 months, 6 months","description":"Diet modifications will be assessed using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24). The ASA24 is a tool from National Cancer Institute (NCI) that enables multiple automatically coded self-administered 24-hour recalls and food records. Changes in total caloric intake, fat, carbohydrate, fiber, sugars, and protein will be evaluated."}]}
{"nct_id":"NCT05043922","start_date":"2021-09-09","phase":"Phase 2","enrollment":228,"brief_title":"A Study to Evaluate the Efficacy and Safety of CYH33 in Patients With Recurrent/Persistent Ovary Clear Cell Carcinoma","official_title":"A Phase II, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of CYH33, a Selective PI3K Inhibitor in Patients With Recurrent/Persistent Ovary, Fallopian Tube or Primary Peritoneal Clear Cell Carcinoma","primary_completion_date":"2023-06-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-06-30","last_update":"2021-09-14","description":"The purpose of this study is to determine the treatment efficacy of CYH33 monotherapy in patients with recurrent or persistent ovarian, fallopian tube or primary peritoneal clear cell carcinoma, who received prior systemic anti-tumor treatment.","other_id":"CYH33-G201","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Main Inclusion Criteria:\r\n\r\n          1. Female patients  18 years of age\r\n\r\n          2. Provide informed consent voluntarily.\r\n\r\n          3. Patients must have histologically or cytologically confirmed recurrent or persistent\r\n             ovarian, fallopian tube, or peritoneum clear cell carcinoma.\r\n\r\n          4. Patients with recurrent/persistent ovary, fallopian tube or primary peritoneal clear\r\n             cell carcinoma, who have identified PIK3CA status (with or without PIK3CA hotspot\r\n             mutations).\r\n\r\n          5. Patients must have failed standard chemotherapy.\r\n\r\n          6. ECOG-PS  1.\r\n\r\n          7. Patient must have adequate organ and bone marrow function measured within 28 days of\r\n             screening.\r\n\r\n        Main Exclusion Criteria:\r\n\r\n        Patients are ineligible for this study if they meet any of the following criteria:\r\n\r\n          1. Patient has received any anticancer therapy\r\n\r\n          2. Patients who had prior treatment with any PI3K, mTOR or AKT inhibitor.\r\n\r\n          3. Radical radiation therapy within 4 weeks prior to the first dose of the\r\n             investigational product or received local palliative radiation therapy for bone\r\n             metastases within 2 weeks.\r\n\r\n          4. Any toxicities from prior treatment that have not recovered to baseline.\r\n\r\n          5. Patients who have been treated with any hematopoietic colony-stimulating growth\r\n             factors  2 weeks prior to starting study drug.\r\n\r\n          6. Patients who have symptomatic CNS metastasis.\r\n\r\n          7. Major surgery or had significant traumatic injury within 28 days prior to the first\r\n             dose of the investigational product or has not recovered from major side effects.\r\n\r\n          8. Known HIV infection with a history of acquired immunodeficiency syndrome\r\n             (AIDS)-defining opportunity infection within the past 12 months; active hepatitis B\r\n             and hepatitis C.\r\n\r\n          9. History of acute pancreatitis within 1 year of screening or past medical history of\r\n             chronic pancreatitis.\r\n\r\n         10. Patients with clinically significant cardiovascular disease\r\n      ","sponsor":"Haihe Biopharma Co., Ltd.","sponsor_type":"Industry","conditions":"Ovarian Cancer|Recurrent Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: CYH33","description":"a Selective PI3K Inhibitor"}],"outcomes":[{"outcome_type":"primary","measure":"Tumor ORR in patients with PIK3CA hotspot mutations.","time_frame":"through study completion, an average of 1 year","description":"Tumor ORR per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in patients with PIK3CA hotspot mutations."},{"outcome_type":"secondary","measure":"ORR in patients without PIK3CA hotspot mutations.","time_frame":"through study completion, an average of 1 year","description":"ORR per RECIST v1.1 in patients without PIK3CA hotspot mutations."},{"outcome_type":"secondary","measure":"PFS","time_frame":"through study completion, an average of 1 year","description":"PFS by BIRC using RECIST v1.1"},{"outcome_type":"secondary","measure":"OS","time_frame":"through study completion, an average of 2 year","description":"OS in each of the PIK3CA mutation status cohort"},{"outcome_type":"secondary","measure":"genetic and protein biomarker alterations","time_frame":"through study completion, an average of 1 year","description":"genetic and protein biomarker alterations that can impact PI3K signaling pathway"},{"outcome_type":"other","measure":"Safety and tolerability","time_frame":"through study completion, an average of 1 year","description":"type, incidence, duration, severity and seriousness of adverse events (AEs)"},{"outcome_type":"other","measure":"DLT (Dose Limiting Toxicity) in Japanese patients","time_frame":"4 weeks","description":"Number and proportion of patients who experienced DLT during the first 28-day of treatment in Japanese patients in safety run-in study."},{"outcome_type":"other","measure":"Peak Plasma Concentration (Cmax)","time_frame":"4weeks","description":"Pharmacokinetics parameters"},{"outcome_type":"other","measure":"Area under the plasma concentration versus time curve (AUC)","time_frame":"4weeks","description":"Pharmacokinetics parameters"}]}
{"nct_id":"NCT04986423","start_date":"2021-09-08","phase":"Phase 2","enrollment":200,"brief_title":"ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer","official_title":"A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer","primary_completion_date":"2024-03-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-09-30","last_update":"2021-09-10","description":"This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry. The patient population will be separated into two cohorts: Cohort A: Patients with poor response to prior abiraterone defined as: - Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone, or; - Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: < 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone Cohort B: Patients with response to prior abiraterone, defined as: - Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting:  12 months duration on abiraterone and nadir PSA < 0.2 ng/mL, or; - Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting:  6 months duration on abiraterone and confirmed PSA50 response","other_id":"ZEN003694-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Males age  18 years\r\n\r\n          2. Metastatic, castration-resistant, histologically confirmed prostate cancer\r\n\r\n          3. Surgical castration or continuous medical castration for  8 weeks prior to screening;\r\n             serum testosterone < 50 ng/dL confirmed within 4 weeks of first administration of\r\n             study drug\r\n\r\n          4. Have progressed on prior abiraterone treatment by PCWG3 criteria\r\n\r\n          5. Patients who are not candidates for chemotherapy in the opinion of the investigator or\r\n             patients who decline chemotherapy\r\n\r\n          6. Cohort A only - Patient must meet definition of poor responder to abiraterone by one\r\n             of the following:\r\n\r\n               1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting:\r\n                  < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL\r\n                  while taking abiraterone\r\n\r\n               2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting:\r\n                  < 6 months duration on abiraterone or failure to achieve a PSA50 response\r\n\r\n          7. Cohort B only - Patient must meet definition of responder to abiraterone by one of the\r\n             following:\r\n\r\n               1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting:\r\n                   12 months duration on abiraterone and nadir PSA < 0.2 ng/mL\r\n\r\n               2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting:\r\n                   6 months duration on abiraterone and PSA50 response\r\n\r\n          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Any history of brain metastases, prior seizure, conditions predisposing to seizure\r\n             activity\r\n\r\n          2. Have previously received an investigational BET inhibitor (including previous\r\n             participation in this study or a study of ZEN003694)\r\n\r\n          3. Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide,\r\n             apalutamide, darolutamide, proxalutamide). Receipt of first-generation AR antagonists\r\n             (e.g. bicalutamide, nilutamide, flutamide) does not count towards this limit.\r\n\r\n          4. Have received prior chemotherapy in the metastatic castration-resistant setting (prior\r\n             chemotherapy in the hormone-sensitive setting is allowed provided last dose was at\r\n             least 6 months prior to first dose of study drug)\r\n\r\n          5. Have received prior systemic anti-cancer therapy within 2 weeks or five half-lives,\r\n             whichever is shorter, prior to the first administration of study drug\r\n\r\n          6. Have received exogenous administration of testosterone therapy since discontinuation\r\n             of abiraterone.\r\n\r\n          7. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy\r\n             (excluding alopecia and neuropathy) prior to study entry\r\n\r\n          8. Radiation therapy within 2 weeks of the first administration of study drug\r\n      ","sponsor":"Zenith Epigenetics","sponsor_type":"Industry","conditions":"Metastatic Castration-Resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ZEN003694","description":"72 mg PO QD"},{"intervention_type":"Drug","name":"Drug: Enzalutamide","description":"160 mg PO QD"}],"outcomes":[{"outcome_type":"primary","measure":"Cohort A: Radiographic progression-free survival (rPFS) by BICR","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3."},{"outcome_type":"secondary","measure":"Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3"},{"outcome_type":"secondary","measure":"Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3."},{"outcome_type":"secondary","measure":"Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3."},{"outcome_type":"secondary","measure":"Cohort A: Progression-free survival (PFS) by investigator assessment","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment."},{"outcome_type":"secondary","measure":"Cohort A + B: Progression-free survival (PFS) by investigator assessment","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment."},{"outcome_type":"secondary","measure":"Cohort A: Overall survival (OS)","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of death from any cause"},{"outcome_type":"secondary","measure":"Cohort A + B: Overall survival (OS)","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the date of death from any cause"},{"outcome_type":"secondary","measure":"Cohort A: PSA50 response rate","time_frame":"Randomization up to 30 months","description":"PSA response is a reduction in serum PSA concentration of ≥50% from baseline."},{"outcome_type":"secondary","measure":"Cohort A + B: PSA50 response rate","time_frame":"Randomization up to 30 months","description":"PSA response is a reduction in serum PSA concentration of ≥50% from baseline."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"Randomization up to 30 months","description":"Proportion of the patients who have either a complete response (CR) or partial response (PR) by RECIST 1.1 criteria who have measurable disease at baseline."},{"outcome_type":"secondary","measure":"Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)","time_frame":"Screening and Day 1 of every 28-day Cycle up to 30 months","description":"EORTC QLQ-C30: cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning."},{"outcome_type":"secondary","measure":"Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Module (EORTC QLQ-PR25).","time_frame":"Screening and Day 1 of every 28-day Cycle up to 30 months","description":"EORTC QLQ-PR25: prostate cancer specific instrument with 25 questions used in conjunction with EORTC QLQ-C30 to assess the participant QoL. Used to evaluate 5 multi-item scales (urinary, bowel, and hormonal treatment-related symptoms, sexual activity, and sexual functioning) and one single item (problems due to incontinence aid use). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning."},{"outcome_type":"secondary","measure":"Time to initiation of chemotherapy","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the first dose of chemotherapy."},{"outcome_type":"secondary","measure":"Time to first skeletal related event (SRE)","time_frame":"Randomization up to 30 months","description":"Time from date of randomization to the first SRE such as pathological fracture, surgery/radiotherapy for pain/prevention of fracture, hypercalcemia, and spinal cord compression."},{"outcome_type":"secondary","measure":"Measure plasma concentrations of ZEN003694 and the active metabolite ZEN003791","time_frame":"Cycle 1 Day 1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose; Cycle 2 Day1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose","description":"Plasma concentrations of ZEN003694 and the active metabolite ZEN003791 will be measured."}]}
{"nct_id":"NCT04969731","start_date":"2021-09-07","phase":"Phase 3","enrollment":408,"brief_title":"Safety and Efficacy of Immuncell-LC With Gemcitabine in Resectable Pancreatic Cancer","official_title":"An Open-label, Randomized, Multi-center, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Immuncell-LC Therapy Combined With Gemcitabine Versus Adjuvant Gemcitabine Single Therapy After Resection in Patients With Pancreatic Ductal Adenocarcinoma","primary_completion_date":"2026-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-06-30","last_update":"2021-09-14","description":"PURPOSE: This phase III clinical trial evaluates the efficacy and safety of adjuvant Immuncell-LC therapy combined with gemcitabine versus adjuvant gemcitabine single therapy after R0 or R1 resection in patients with pancreatic ductal adenocarcinoma.","other_id":"ILC-P3-PAN","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":19,"maximum_age":80,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Age >/=20 years old, <\/=80 years old.\r\n\r\n          2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma that\r\n             fulfill the following requirements:\r\n\r\n               -  Participants have undergone a radical full resection (R0) or boundary resection\r\n                  (R1) operation and has elapsed at least two weeks after the resection based on\r\n                  the baseline, up to 12 weeks.\r\n\r\n               -  Noncancerous ascites.\r\n\r\n               -  No evidence of distant metastasis (such as liver, peritoneum)\r\n\r\n               -  No evidence of distant metastasis in other distant abdominal or extra-abdominal\r\n                  organs\r\n\r\n               -  Scheduled to be given gemcitabine alone as postoperative adjuvant chemotherapy\r\n\r\n          3. Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 - 2\r\n\r\n          4. Life expectancy is at least 12 weeks.\r\n\r\n          5. Adequate organ and marrow function at the screening and baseline as defined below:\r\n\r\n               -  Absolute neutrophil count  1,500/L\r\n\r\n               -  Hemoglobin level  9 g/dL\r\n\r\n               -  Platelet count  100,000/L\r\n\r\n               -  BUN, serum creatinine  1.5  institutional upper limit of normal (ULN)\r\n\r\n               -  AST, ALT  2.5  institutional upper limit of normal (ULN)\r\n\r\n               -  PT (INR), activated partial thromboplastin time (aPTT)  1.5  institutional\r\n                  upper limit of normal (ULN)\r\n\r\n          6. Ability to understand and the willingness to sign a written informed consent document.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Received anticancer therapy including chemotherapy, biological therapy, immunotherapy,\r\n             hormone therapy, radiation therapy, and other anti-cancer treatments. Note:\r\n             Neo-adjuvant therapy for pancreatic cancer is allowed.\r\n\r\n          2. Measurable lesions identified in the pancreas after surgery.\r\n\r\n          3. Known history at the screening as defined below.\r\n\r\n               -  Confirmed cases of acquired immunodeficiency, which can be exacerbated by\r\n                  immunotherapy.\r\n\r\n               -  History of autoimmune diseases that can be exacerbated by immunotherapy. (e.g.\r\n                  rheumatoid arthritis, systemic lupus, vascular inflammation, multiple sclerosis,\r\n                  adolescent-induced insulin-dependent diabetes, T-cell lymphoma, etc.)\r\n\r\n               -  Active hepatitis B or hepatitis C virus infection confirmed.\r\n\r\n               -  Human immunodeficiency virus (HIV) antibody test results are positive during\r\n                  screening\r\n\r\n               -  History of malignant tumors other than pancreatic cancer within five years of\r\n                  screening. Note: skin basal cell cancer/squamous cell cancer, local prostate\r\n                  cancer, thyroid papillary cancer or cervical epithelial cancer can be\r\n                  participated even if 5 years have passed since successful treatment.\r\n\r\n          4. Known associated disease at the screening as defined below.\r\n\r\n               -  Severe nephropathy: estimated glomerular filtration rate (eGFR) <30 mL/min/1.73\r\n                  m2\r\n\r\n               -  Chest X-ray shows epileptic pneumonia or pulmonary fibrosis with clear, clinical\r\n                  symptoms.\r\n\r\n               -  Severe infections or other uncontrolled active infectious diseases requiring the\r\n                  administration of antibiotics, antibacterial drugs, antifungal drugs, antiviral\r\n                  drugs, etc. that may affect safety and validity evaluation during clinical\r\n                  trials, as determined by the tester.\r\n\r\n               -  Holder of thromboembolic disease or bleeding diatheses\r\n\r\n               -  Those who are deemed unfit to participate in clinical trials because they are not\r\n                  controlled or require treatment (e.g., heart disease, pulmonary dysfunction,\r\n                  renal dysfunction, low blood pressure, hypertension, bone marrow inhibition,\r\n                  liver metastasis, hepatitis, history of alcoholism, myocardial infarction, etc.)\r\n\r\n          5. Received Immuncell-LC, Natural Killer (NK) cell therapy or other cell therapy drugs\r\n             within three years prior to screening.\r\n\r\n          6. Anaphylaxis to the main ingredient or sub-brothers of Immuncell-LC or Gemcitabine\r\n\r\n          7. Patients who cannot collect blood for manufacturing Immuncell-LC depending on the\r\n             investigator's judgment.\r\n\r\n          8. Pregnant or lactating women\r\n\r\n          9. Fertility women and men who are not willing to use appropriate contraception from\r\n             screening to 24 weeks after final administration of Immuncell-LC and/or Gemgitabine\r\n\r\n         10. Received or applied with another investigational products or investigational device\r\n             within 4 weeks prior to signing a written informed consent document.\r\n\r\n         11. Patients who are inappropriate or impossible to participate in the trial due to\r\n             non-recovery of resection or prior chemotherapy depending on the investigator's\r\n             judgment.\r\n      ","sponsor":"Green Cross Cell Corporation","sponsor_type":"Industry","conditions":"Pancreatic Ductal Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Immuncell-LC","description":"IV"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"IV"}],"outcomes":[{"outcome_type":"primary","measure":"Recurrence free survival (RFS) by independent review","time_frame":"Up to approximately 36 months after Last Patient In","description":"Recurrence free survival is defined as the time from randomization to the date of the recurrence confirmed by independent reviewer"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to approximately 36 months after Last Patient In","description":"Overall survival is defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Recurrence free survival (RFS) by investigator","time_frame":"Up to approximately 36 months after Last Patient In","description":"Recurrence free survival is defined as the time from randomization to the date of the recurrence confirmed by investigator"},{"outcome_type":"secondary","measure":"Carbohydrate antigen 19-9 level","time_frame":"Up to approximately 36 months after Last Patient In","description":"Carbohydrate antigen 19-9 level"},{"outcome_type":"secondary","measure":"Quality of Life (QoL) EORTC QLQ-C30","time_frame":"Up to approximately 36 months after Last Patient In","description":"The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A higher score represents a higher (\"better\") level of functioning, or a higher (\"worse\") level of symptoms."},{"outcome_type":"secondary","measure":"Quality of Life (QoL) EORTC QLQ-PAN26","time_frame":"Up to approximately 36 months after Last Patient In","description":"The module comprises 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). The answers range is the following: not at all - 1 point, a little - 2 points, quite a bit - 3 points, very much - 4 points. Minimum score is 26, maximum is 106. The higher total score represents the worse quality of life."}]}
{"nct_id":"NCT05015621","start_date":"2021-09-05","phase":"Phase 3","enrollment":194,"brief_title":"A Phase 3 Study to Evaluate Surufatinib Plus Toripalimab in the Treatment of Advanced Neuroendocrine Carcinoma","official_title":"A Phase 3, Randomized, Open-label, Multi-center Study to Evaluate the Efficacy and Safety of Surufatinib Plus Toripalimab Versus FOLFIRI as a Secondline Treatment in Patients With Advanced Neuroendocrine Carcinoma","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-11-30","last_update":"2021-08-20","description":"To evaluate the efficacy of Surufatnib combined with Toripalimab compared with FOLFIRI in the treatment of advanced neuroendocrine carcinoma","other_id":"2021-012-00CH1","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients who included in this study must fulfil all of the following criteria:\r\n\r\n               1. Fully aware of this study and voluntary to sign the informed consent form (the\r\n                  informed consent form must be signed before any trial-specific procedure is\r\n                  performed);\r\n\r\n               2. Aged 18~75 years (inclusive);\r\n\r\n               3. Histologically or cytologically confirmed, unresectable, locally advanced or\r\n                  metastatic neuroendocrine carcinoma\r\n\r\n               4. Patients with neuroendocrine carcinoma who have failed previous platinum-based\r\n                  1st-line chemotherapy\r\n\r\n               5. ECOG performance status of 0 or 1 ;\r\n\r\n               6. Having clear measurable lesions as defined by RECIST v1.1;\r\n\r\n               7. Patients who agree to provide tumor specimens for diagnosis of pathological type\r\n                  and detection of expression levels of PD-L1 and other biomarkers;\r\n\r\n               8. Patients with adequate bone marrow, liver and kidney organ functions whose\r\n                  laboratory tests within 7 days before the first dose meet the following\r\n                  requirements:\r\n\r\n                    1. Absolute neutrophil count (ANC) 1.5109/L, platelet count 100109/L and\r\n                       hemoglobin 90 g/dL (without blood transfusion or use of blood products for\r\n                       correction within 14 days prior to laboratory examination, and without use\r\n                       of granulocyte colony stimulating factor or other hematopoietic stimulating\r\n                       factor for correction within 7 days prior to laboratory examination);\r\n\r\n                    2. Serum total bilirubin 1.5  upper limit of normal (ULN);\r\n\r\n                    3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 \r\n                       ULN in the absence of liver metastases; ALT and AST 5  ULN in the presence\r\n                       of liver metastases.\r\n\r\n                    4. Serum creatinine  1.5  ULN and creatinine clearance  50 mL/min\r\n                       (calculated according to the Cockcroft-Gault formula, see Appendix 3);\r\n\r\n                    5. Routine urinalysis showing urine protein < 2+; in case of urine protein \r\n                       2+, 24-hour urine protein (quantitative) should be <1g;\r\n\r\n                    6. International normalized ratio (INR)  1.5 and activated partial\r\n                       thromboplastin time (APTT) 1.5  ULN.\r\n\r\n               9. Estimated survival  12 weeks;\r\n\r\n              10. Females of childbearing potential must have a negative serum pregnancy test\r\n                  within 7 days prior to the first dose. Male or female patients of childbearing\r\n                  potential volunteer to use effective contraceptive methods during the study and\r\n                  within 90 days after last administration of the study drug, such as double\r\n                  barrier contraception, condoms, oral or injectable contraceptives, intrauterine\r\n                  contraceptive device, etc. All female patients will be considered to be of\r\n                  childbearing potential unless they are naturally postmenopausal, underwent\r\n                  artificial menopause, or are surgically sterile (e.g., hysterectomy, bilateral\r\n                  adnexectomy).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects must be excluded from this study when any one of the following criteria is\r\n             met:\r\n\r\n               1. Toxicities associated with previous anti-tumor treatment do not return to CTCAE\r\n                  grade 1, except for alopecia and peripheral neurotoxicity ( CTCAE grade 2 )\r\n                  caused by Oxaliplatin;\r\n\r\n               2. Presence of other malignancies in the past 5 years (except for basal cell\r\n                  carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the\r\n                  cervix, which were effectively controlled);\r\n\r\n               3. Presence of central nervous system (CNS) metastases in screening period;\r\n\r\n               4. Use of approved systematic anti-tumor therapy within 4 weeks prior to the first\r\n                  dose, including chemotherapy, biotherapy, targeted therapy (the washout period of\r\n                  small molecular targeted drugs lasts 2 weeks or 5 half-lives, whichever is\r\n                  shorter), hormone therapy, treatments with traditional Chinese medicine (for\r\n                  patients receiving treatments with traditional Chinese medicine with clear\r\n                  anti-tumor indications, for anti-tumor indications clearly specified in the\r\n                  package insert, one-week washout period prior to the first dose is acceptable),\r\n                  etc.;\r\n\r\n               5. Use of radical radiotherapy (including radiotherapy for more than 25% of the bone\r\n                  marrow) within 4 weeks before the first dose; brachytherapy (e.g. radioactive\r\n                  particle implantation) within 60 days prior to the first dose; palliative\r\n                  radiotherapy for bone metastases within 1 week before the first dose;\r\n\r\n               6. Previous use of anti (PD-1), anti-PD-L1, anti-PD-L2 or CTLA-4 antibody or any\r\n                  other antibody acting on T cell co-stimulatory or checkpoint pathways\r\n\r\n               7. Previous use of vascular endothelial growth factor (VEGF)/vascular endothelial\r\n                  growth factor receptor (VEGFR) targeted therapy;\r\n\r\n               8. Previous therapy with Irinotecan;\r\n\r\n               9. Having abnormal thyroid function with symptoms ongoing or requiring treatment at\r\n                  screening ;\r\n\r\n              10. Use of immunosuppressant within 4 weeks prior to the first dose, not including\r\n                  local glucocorticoid via nasal spray, inhalation or other routes or systemic\r\n                  glucocorticoid at physiological dose (i.e., no more than 10mg/day of prednisone\r\n                  or equivalent dose), temporary use of glucocorticoid for treatment of dyspnea\r\n                  resulted from asthma, chronic obstructive pulmonary disease is allowed, and\r\n                  preventive use of corticosteroid to avoid allergic reactions is allowed\r\n\r\n              11. Patients with any active autoimmune disorders requiring systematic treatment or a\r\n                  history of autoimmune disease in the past 2 years,\r\n\r\n              12. Use of systemic immune stimulants within 4 weeks prior to the first dose;\r\n\r\n              13. Vaccination of any live or attenuated live vaccine within 4 weeks prior to the\r\n                  first dose or during the study.\r\n\r\n              14. Patients having received major surgical operation within 4 weeks prior to the\r\n                  first dose .\r\n\r\n              15. Uncontrollable malignant hydrothorax, ascites or pericardial effusion ;\r\n\r\n              16. Patients who currently have hypertension that cannot be controlled by medication.\r\n\r\n              17. Patients who currently have any disease or condition that affects drug\r\n                  absorption, or patient who cannot take the drug orally;\r\n\r\n              18. Use of CYP3A potent or moderate inducers during the administration of concomitant\r\n                  medications or within 2 weeks or 5 half-lives (whichever is longer) prior to the\r\n                  first dose;\r\n\r\n              19. Patients who currently have gastric and duodenal active ulcer, ulcerative\r\n                  colitis, or active bleeding in the unresected tumor, or serious gastrointestinal\r\n                  disorders , or other conditions that may cause haemorrhage of digestive tract or\r\n                  perforation\r\n\r\n              20. Patients with evidence or history of obvious bleeding tendency within 2 months\r\n                  prior to the first dose\r\n\r\n              21. Arterial thrombosis or deep venous thrombosis occurred within 6 months prior to\r\n                  the first dose; or stroke events and/or transient ischemic attacks occurred\r\n                  within 12 months.\r\n\r\n              22. Clinically significant cardiovascular disorder,\r\n\r\n              23. Presence of clinically significant electrolyte abnormality judged by the\r\n                  investigator;\r\n\r\n              24. Patients with active infection or fever of unknown origin during screening and\r\n                  prior to the first dose (body temperature >38.5C);\r\n\r\n              25. Patients with active tuberculosis (TB), receiving anti-tuberculosis therapy\r\n                  currently or within one year prior to the first dose;\r\n\r\n              26. Patients with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis,\r\n                  radiation pneumonitis, drug-related pneumonia, serious lung function impairment\r\n                  that may interfere with the detection and management of suspected drug-related\r\n                  pulmonary toxicities; radiation pneumonitis in the area of radiotherapy is\r\n                  allowed;\r\n\r\n              27. Human immunodeficiency virus (HIV) antibody positive;\r\n\r\n              28. Patients with known history of clinically significant liver diseases, including\r\n                  those infected with active viral hepatitis [HBV DNA > 1  104 copies/mL or > 2000\r\n                  IU/mL when hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody\r\n                  (HbcAb) is positive; patients with known positive hepatitis C virus antibody (HCV\r\n                  Ab) and HCV RNA > 1  103 copies/mL], or other hepatitis, including moderate and\r\n                  severe hepatic cirrhosis with a clinical significance;\r\n\r\n              29. Use of clinical drug treatment which has not been approved or marketed in China\r\n                  within 4 weeks prior to the first dose;\r\n\r\n              30. Pregnant (positive pregnancy test prior to administration) or lactating women;\r\n\r\n              31. Patients with known allergy to any component of toripalimab, surufatnib or\r\n                  Irinotecan, fluorouracil and calcium folinate preparations, or previous history\r\n                  of serious allergy to any other monoclonal antibody;\r\n\r\n              32. Patients with other reasons that, in the opinion of the investigator, make it\r\n                  unsuitable to participate in this clinical study.\r\n      ","sponsor":"Hutchison Medipharma Limited","sponsor_type":"Industry","conditions":"Advanced Neuroendocrine Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Surufatinib plus Toripalimab","description":"Surufatinib is a tablet in the form of 50mg, oral, once a day; Toripalimab is an injection in the form of 240mg, intravenous, once three weeks."},{"intervention_type":"Drug","name":"Drug: 5-fluorouracil, Calcium folinate and Irinotecan","description":"Irinotecan 180 mg/m2, Calcium folinate 200 mg/m2, 5-FU total 2800 mg/m2 will be administrated once two weeks."}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)","description":"Duration from the date of initial treatment to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS) (RECIST1.1)","time_frame":"From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years)","description":"A duration from the date of initial treatment to disease progression or death of any cause."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)(RECIST1.1)","time_frame":"From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)]","description":"The incidence of confirmed complete response or partial response"},{"outcome_type":"secondary","measure":"Duration of response (DoR)(RECIST1.1)","time_frame":"From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)]","description":"Duration from the first time reported partial response or complete response to the first time of disease progression or death."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)(RECIST1.1)","time_frame":"From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)]","description":"Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit."},{"outcome_type":"secondary","measure":"PD-L1","time_frame":"Baseline (before the randomization)","description":"To evaluate the relationship between the efficacy and tumor biomarkers of PD-L1"},{"outcome_type":"secondary","measure":"Ki67","time_frame":"Baseline (before the randomization)","description":"To evaluate the relationship between the efficacy and tumor biomarkers of ki67"},{"outcome_type":"secondary","measure":"Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)","time_frame":"From the within 7 days prior to the initiation of treatment to 30 days after the last administration","description":"The changes in health-related quality of life (HRQoL) score from baseline and the time to deterioration of symptoms (TTD) as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)"}]}
{"nct_id":"NCT04349111","start_date":"2021-09-04","phase":"N/A","enrollment":2000,"brief_title":"An Efficacy Study of the Xoft Axxent eBx IORT System \"Lite\"","official_title":"An Efficacy Study of Intra-Operative Radiation Therapy (IORT) Using the Xoft Axxent eBx System at the Time of Breast Conservation Surgery for Early Stage Breast Cancer \"Lite\"","primary_completion_date":"2024-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2030-03-31","last_update":"2021-07-13","description":"The purpose of this trial is to assess the efficacy of the Xoft Axxent eBx System when used for single-fraction IORT in early stage breast cancer. A comparison will be made to the current standard of care, whole breast irradiation (WBI), in women with early stage breast cancer.","other_id":"CTPR-0015","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Single 20Gy dose of electronic brachytherapy (IORT)","sampling_method":"","gender":"Female","minimum_age":40,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Subject must have provided written Informed Consent\r\n\r\n          2. Subject must have biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal\r\n             carcinoma (IDC) of the breast\r\n\r\n          3. Subject must be female  40 years of age\r\n\r\n          4. Subject's tumor(s) must be < 3.0 cm in greatest diameter by pre-operative assessment\r\n\r\n          5. Clinical staging of Subject's tumor(s) must meet AJCC Tumor Classification: Tis, T1 or\r\n             T2 (< 3 cm), N0, M0\r\n\r\n          6. Subject presenting with bilateral breast cancer may be enrolled if BOTH cancers meet\r\n             all of the inclusion and none of the exclusion criteria\r\n\r\n          7. Women of child-bearing potential must have a negative pregnancy test within one week\r\n             of IORT treatment\r\n\r\n          8. Women of child-bearing potential must agree to use adequate contraceptive precautions\r\n             (defined as intrauterine devices, surgical contraceptives or a combination of condom\r\n             and spermicide) from the time of negative pregnancy test through completion of the\r\n             radiation treatment period\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Subject is pregnant or nursing\r\n\r\n          2. Subject has active auto-immune disease\r\n\r\n          3. Subject has a pacemaker present in the field of radiation or quadrant of the breast\r\n             cancer\r\n\r\n          4. Subject has multi-focal breast cancer where the sum of the individual tumor sizes\r\n             (greatest diameters) are > 3 cm\r\n\r\n          5. Subject has multi-centric breast cancer\r\n\r\n          6. Subject has known lympho-vascular invasion\r\n\r\n          7. Subject has invasive lobular cancer\r\n\r\n          8. Subject has undergone neo-adjuvant chemotherapy or neo-adjuvant endocrine therapy for\r\n             current breast cancer\r\n\r\n          9. Subject has a history of recurrent breast cancer in the ipsilateral breast\r\n\r\n         10. Subject has had previous radiation exposure of the involved breast\r\n\r\n         11. Subject has BRCA 1 or 2 mutations. Note: Testing will only be required for subjects\r\n             presenting with bilateral breast cancer; testing is not required for unilateral\r\n             cancers\r\n\r\n         12. Subject has contraindications for radiation\r\n      ","sponsor":"Xoft, Inc.","sponsor_type":"Industry","conditions":"Invasive Ductal Carcinoma|Ductal Carcinoma In Situ","interventions":[{"intervention_type":"Radiation","name":"Radiation: Intra-operative Radiation Therapy - IORT","description":"Single dose of 20 Gy"}],"outcomes":[{"outcome_type":"primary","measure":"Assess the rate of ipsilateral breast tumor recurrence (IBTR) at 5 years","time_frame":"Reported at 5 years","description":"To assess the rate of ipsilateral breast tumor recurrence in subjects treated with the Xoft Axxent Electronic Brachytherapy System when used for single-fraction, intra-operative radiation therapy treatment of early stage breast cancer when compared to whole breast irradiation (WBI) at 5 years of follow-up"}]}
{"nct_id":"NCT04959981","start_date":"2021-09-02","phase":"Phase 1/Phase 2","enrollment":200,"brief_title":"A Study of ERAS-007 in Patients With Advanced Non-Small-Cell Lung Cancer","official_title":"A Phase 1b/2, Open-Label, Multicenter Study of ERAS-007 in Combination With Other Anti-Cancer Therapies in Patients With Advanced Non-Small-Cell Lung Cancer","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-03-31","last_update":"2021-09-16","description":"- To evaluate the safety and tolerability of escalating doses of ERAS-007 in combination with other cancer therapies in study participants with advanced non-small cell lung cancer (NSCLC). - To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with other cancer therapies. - To evaluate the antitumor activity of ERAS-007 in combination with other cancer therapies. - To evaluate the PK profiles of ERAS-007 and other cancer therapies when administered in combination.","other_id":"ERAS-007-02","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":99,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Age  18 years.\r\n\r\n          -  Willing and able to give written informed consent.\r\n\r\n          -  Have histologically or cytologically confirmed advanced NSCLC harboring EGFR\r\n             mutation(s) sensitive to EGFR inhibitors at initial diagnosis per local approved\r\n             label.\r\n\r\n          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\r\n\r\n          -  Adequate bone marrow and organ function.\r\n\r\n          -  Have ECOG performance status of 0 or 1.\r\n\r\n          -  Willing to comply with all protocol-required visits, assessments, and procedures.\r\n\r\n          -  Able to swallow oral medication.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Concurrent treatment with any systemic anticancer therapy for NSCLC, including any\r\n             approved or investigational agent.\r\n\r\n              Prior therapy with a RAS, RAF, MEK, or ERK inhibitor.\r\n\r\n          -  Prior cancer immunotherapy (CIT) (e.g., immune checkpoint inhibitors), unless the CIT\r\n             was followed by a non-CIT containing regimen prior to study enrollment\r\n\r\n               -  Anticancer treatment within 21 days of enrollment, except for osimertinib which\r\n                  may be continued during the screening period.\r\n\r\n               -  Palliative radiotherapy within 7 days of enrollment.\r\n\r\n          -  History of unacceptable toxicity to treatment with osimertinib.\r\n\r\n              Major surgery within the 28 days of enrollment.\r\n\r\n          -  Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at\r\n             time of enrollment, except alopecia and grade 2 neuropathy due to prior chemotherapy.\r\n\r\n          -  Any evidence of severe or uncontrolled systemic disease or evidence of any other\r\n             significant clinical disorder or laboratory finding that renders the patient\r\n             inappropriate to participate in the study.\r\n\r\n          -  Impaired cardiovascular function or clinically significant cardiovascular disease.\r\n\r\n          -  History or current evidence of retinal pigment epithelial detachment (RPED), central\r\n             serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or\r\n             RVO.\r\n\r\n          -  Pregnant or breastfeeding women.\r\n\r\n          -  Contraindication to osimertinib use as per local label.\r\n      ","sponsor":"Erasca, Inc.","sponsor_type":"Industry","conditions":"Advanced Non-squamous Non-small-cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ERAS-007","description":"ERAS-007 will be administered orally as specified in Arm description."},{"intervention_type":"Drug","name":"Drug: osimertinib","description":"80 mg orally once daily"}],"outcomes":[{"outcome_type":"primary","measure":"Dose Limiting Toxicities (DLT)","time_frame":"Study Day 1 up to Day 22","description":"Based on adverse events observed"},{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD)","time_frame":"Study Day 1 up to Day 22","description":"Based on adverse events observed"},{"outcome_type":"primary","measure":"Recommended Dose (RD)","time_frame":"Study Day 1 up to Day 22","description":"Based on adverse events observed"},{"outcome_type":"primary","measure":"Adverse Events","time_frame":"Assessed up to 24 months from time of first dose","description":"Incidence and severity of treatment-emergent AEs and serious AEs"},{"outcome_type":"secondary","measure":"Plasma concentration (Cmax)","time_frame":"Study Day 1 up to Day 22","description":"Maximum plasma concentration of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Time to achieve Cmax (Tmax)","time_frame":"Study Day 1 up to Day 22","description":"Time to achieve maximum plasma concentration of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Area under the curve","time_frame":"Study Day 1 up to Day 22","description":"Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Half-life","time_frame":"Study Day 1 up to Day 22","description":"Half-life of ERAS-007 and other cancer therapies"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Assessed up to 24 months from time of first dose","description":"Based on assessment of radiographic imaging per RECIST version 1.1"},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Assessed up to 24 months from time of first dose","description":"Based on assessment of radiographic imaging per RECIST version 1.1"}]}
{"nct_id":"NCT05009290","start_date":"2021-09-01","phase":"Phase 3","enrollment":1256,"brief_title":"A Trial of SHR3680 in Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy","official_title":"A Phase III Randomized, Placebo-Controlled, Double-Blind Study of SHR3680 Plus Androgen Deprivation Therapy (ADT) Versus ADT in Patients With High-Risk Localized or Locally Advanced Prostate Cancer Undergoing Radical Prostatectomy","primary_completion_date":"2027-10-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2031-10-30","last_update":"2021-08-17","description":"The study is being conducted to evaluate the efficacy and safety of SHR3680 plus androgen deprivation therapy (ADT) vs. placebo plus ADT in patients with high-risk localized or locally advanced prostate cancer using pathologic complete response (pCR) rate and metastasis-free survival (MFS).","other_id":"SHR3680-III-302","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","intervention_model_description":"SHR3680 + ADT compared with placebo + ADT","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Age of  18 years old;\r\n\r\n          2. ECOG PS score of 0 or 1;\r\n\r\n          3. Pathologically diagnosed as prostate adenocarcinoma;\r\n\r\n          4. High-risk patients\r\n\r\n          5. No distant metastasis (clinical staging of M0) as determined by BICR of imaging\r\n             examinations;\r\n\r\n          6. Subjects who are candidates for and plan to undergo radical prostatectomy (removal of\r\n             the entire prostate and seminal vesicle plus pelvic lymphadenectomy);\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Subjects who received any prior treatment for prostate cancer, except medical ADT\r\n             and/or first-generation androgen receptor antagonists (such as bicalutamide) for not\r\n             more than 4 weeks;\r\n\r\n          2. Subjects who received any other investigational products or underwent major surgery\r\n             within 4 weeks prior to randomization;\r\n\r\n          3. Subjects who are planning bilateral orchidectomy during the treatment period of the\r\n             study;\r\n\r\n          4. Subjects with dysphagia, chronic diarrhea, intestinal obstruction, or other factors\r\n             affecting drug intake and absorption;\r\n\r\n          5. Subjects with a history of epilepsy, or diseases that can induce seizures occurred\r\n             within 12 months prior to randomization (including a history of transient ischemic\r\n             attack, stroke, traumatic brain injury, and cognitive impairment, requiring\r\n             hospitalization);\r\n\r\n          6. Subjects with active heart disease within 6 months prior to randomization, including:\r\n             severe/unstable angina pectoris, myocardial infarction, symptomatic congestive heart\r\n             failure, and ventricular arrhythmias requiring medical treatment;\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Patients With High-risk Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy","interventions":[{"intervention_type":"Drug","name":"Drug: SHR3680","description":"Treatment group: SHR3680 240 mg orally once daily before or after breakfast, 28 days per cycle for a total of 12 treatment cycles (6 cycles before and 6 cycles following radical prostatectomy).\r\nGoserelin acetate sustained-release depot: 10.8 mg administered subcutaneously into the anterior abdominal wall once every 3 cycles (12 weeks) for a total of 12 cycles."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Treatment group Placebo 240 mg orally once daily before or after breakfast, 28 days per cycle for a total of 12 treatment cycles (6 cycles before and 6 cycles following radical prostatectomy).\r\nGoserelin acetate sustained-release depot: 10.8 mg administered subcutaneously into the anterior abdominal wall once every 3 cycles (12 weeks) for a total of 12 cycles."}],"outcomes":[{"outcome_type":"primary","measure":"pCR rate (assessed by pathology BICR)","time_frame":"36 months since the first subject will be enrolled.","description":"Defined as the proportion of subjects with no residual tumor detected in prostatectomy specimens by H&E staining and ancillary immunohistochemistry (if necessary) as assessed by pathology BICR."},{"outcome_type":"primary","measure":"MFS (assessed by imaging BICR).","time_frame":"84 months since the first subject will be enrolled.","description":"Defined as the time from the date of randomization to the date of first occurrence of BICR-confirmed radiographic distant metastasis, accidental pathologic finding of distant metastasis, or death from any cause (whichever occurs first), regardless of whether the subject reveives any other anti-tumor therapy or has missing (or unevaluable) tumor assessments."},{"outcome_type":"secondary","measure":"MFS (investigator-assessed).","time_frame":"84 months since the first subject will be enrolled.","description":"Defined as the time from the date of randomization to the date of first occurrence of investigator-assessed radiographic distant metastasis to the bone or soft tissue, accidental pathologic finding of distant metastasis, or death from any cause (whichever occurs first), regardless of subsequent anti-tumor treatment or missing (or unevaluable) tumor assessments."},{"outcome_type":"secondary","measure":"PSA response rate.","time_frame":"25 months since the first subject will be enrolled.","description":"Defined as the proportion of subjects with a ≥ 90% decrease in PSA levels from baseline on Day 1 of Cycle 4."},{"outcome_type":"secondary","measure":"PSM rate.","time_frame":"31 months since the first subject will be enrolled.","description":"Defined as the proportion of subjects without tumor cells detected in the margin of prostatectomy pathological specimens following H&E staining and ancillary immunohistochemistry (if necessary), as assessed by local pathologists."},{"outcome_type":"secondary","measure":"Time to BCR.","time_frame":"42 months since the first subject will be enrolled.","description":"Defined as the time from the date of randomization to the time of BCR (i.e. two consecutive PSA rise ≥ 0.2 ng/mL following radical prostatectomy)."}]}
{"nct_id":"NCT05024045","start_date":"2021-08-31","phase":"Phase 1","enrollment":286,"brief_title":"Study of Oral LOXO-338 in Patients With Advanced Blood Cancers","official_title":"A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies","primary_completion_date":"2024-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-30","last_update":"2021-08-27","description":"The purpose of this study is to find out whether the study drug, LOXO-338, is safe and effective in patients with advanced blood cancer. Patients must have already received standard therapy. The study may last up to approximately 3 years.","other_id":"LOXO-BCL-20001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  B-cell malignancy.\r\n\r\n          -  Patients must have received prior therapy.\r\n\r\n          -  Patients must have an objective indication for therapy.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.\r\n\r\n          -  Anticipated life expectancy of greater than or equal to () 12 weeks.\r\n\r\n          -  Adequate bone marrow function.\r\n\r\n          -  Adequate hepatic function.\r\n\r\n          -  Creatinine clearance of  60 milliliters (mL)/minute.\r\n\r\n          -  Ability to swallow tablets.\r\n\r\n          -  Ability to comply with outpatient treatment, laboratory monitoring, and required\r\n             clinic visits for the duration of study participation.\r\n\r\n          -  Prior treatment-related adverse events (AEs) must have recovered to grade less than or\r\n             equal to () 1 or pretreatment baseline, with the exception of alopecia.\r\n\r\n          -  Men with partners of childbearing potential or women of childbearing potential (WOCBP)\r\n             must agree to use highly effective birth control.\r\n\r\n          -  WOCBP must not be pregnant.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior to identification of the RP2D (Dose Expansion) of LOXO-338, a history of known,\r\n             active or suspected:\r\n\r\n               -  Richter's transformation to diffuse large B-cell lymphoma (DLBCL),\r\n                  prolymphocyticleukemia, or Hodgkin lymphoma\r\n\r\n               -  Transformed low grade lymphoma\r\n\r\n               -  Burkitt or Burkitt-like lymphoma\r\n\r\n               -  Multiple myeloma\r\n\r\n               -  Lymphoblastic lymphoma or leukemia\r\n\r\n               -  Posttransplant lymphoproliferative disorder\r\n\r\n          -  Known or suspected history of central nervous system (CNS) involvement.\r\n\r\n          -  History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen\r\n             receptor-modified T cell (CAR-T) therapy within the past 60 days and with any of the\r\n             following:\r\n\r\n               -  Active graft versus host disease (GVHD)\r\n\r\n               -  Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T\r\n                  therapy\r\n\r\n               -  Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms\r\n                  of neurotoxicity Grade > 1 from CAR-T therapy\r\n\r\n               -  Ongoing immunosuppressive therapy\r\n\r\n          -  Known human immunodeficiency virus (HIV) positive, regardless of cluster of\r\n             differentiation 4 (CD4) count. Unknown or negative status eligible.\r\n\r\n          -  Inability to take necessary uric acid lowering agents (i.e., allopurinol, rasburicase,\r\n             orfebuxostat).\r\n\r\n          -  Concurrent anticancer therapy.\r\n\r\n          -  Concurrent treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers\r\n             that can include antifungals.\r\n\r\n          -  Use of  20 milligrams (mg) prednisone once a day (QD) or equivalent dose of steroid\r\n             per day, within 7 days of start of study treatment. Patients may not be on any dose of\r\n             prednisone intended for antineoplastic use.\r\n\r\n          -  Vaccination with a live vaccine within 28 days prior to start of study therapy, with\r\n             the exception of vaccinations for coronavirus disease 2019 (COVID-19), as applicable.\r\n             Live vaccination for COVID-19 should occur at least two weeks prior to cycle 1, day 1\r\n             (C1D1).\r\n\r\n          -  Major surgery within four weeks of planned start of study therapy Prolongation of the\r\n             QT interval corrected by Fridericia's Formula for heart rate (QTcF) greater than (>)\r\n             470 milliseconds (msec).\r\n\r\n          -  Clinically significant cardiovascular disease.\r\n\r\n          -  Female patient who is pregnant or lactating.\r\n\r\n          -  Active second malignancy which may preclude assessment of DLT.\r\n\r\n          -  Clinically significant active malabsorption syndrome including surgical resection of\r\n             small intestine or other condition likely to affect gastrointestinal (GI) absorption\r\n             of the orally administered study drugs.\r\n\r\n          -  Active hepatitis B or C infection.\r\n\r\n          -  Evidence of other clinically significant uncontrolled condition(s) including, but not\r\n             limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other\r\n             clinically significant active disease process.\r\n\r\n          -  Active uncontrolled auto-immune cytopenia.\r\n\r\n          -  Additional exclusion criteria for patients enrolled to part 2: LOXO-338 and\r\n             pirtobrutinib combination\r\n\r\n               -  Prior progression or intolerance to pirtobrutinib.\r\n\r\n               -  Patients requiring therapeutic anticoagulation with warfarin.\r\n\r\n               -  Known hypersensitivity to any component or excipient of pirtobrutinib.\r\n\r\n               -  In patients with history of myocardial infarction or congestive heart failure,\r\n                  documented left ventricular ejection fraction (LVEF) by any method of  45\r\n                  percent (%) in the 12 months prior to planned start of study treatment.\r\n\r\n               -  History of uncontrolled or symptomatic arrhythmias including grade  3 arrhythmia\r\n                  on a prior BTK inhibitor.\r\n\r\n               -  History of major bleeding on a prior BTK inhibitor.\r\n\r\n               -  Current treatment with strong permeability glycoprotein (P-gp) inhibitors.\r\n      ","sponsor":"Eli Lilly and Company","sponsor_type":"Industry","conditions":"Leukemia, Lymphocytic, Chronic, B-Cell|Lymphoma, B-cell Marginal Zone|Lymphoma, Non-Hodgkin|Multiple Myeloma|B-cell Lymphoma|Waldenstrom Macroglobulinemia|Lymphoma, Mantle-Cell","interventions":[{"intervention_type":"Drug","name":"Drug: LOXO-338","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Pirtobrutinib","description":"Oral"}],"outcomes":[{"outcome_type":"primary","measure":"Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338","time_frame":"Cycle 1 (28 Days)","description":"Measured by the number of patients with dose-limiting toxicities (DLTs)"},{"outcome_type":"primary","measure":"Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib","time_frame":"Cycle 2 (28 Days)","description":"Measured by the number of patients with dose-limiting toxicities (DLTs)"},{"outcome_type":"secondary","measure":"Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)","time_frame":"Predose up to 24 hours postdose","description":"PK: AUC of LOXO-338"},{"outcome_type":"secondary","measure":"Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)","time_frame":"Predose up to 24 hours postdose","description":"PK: Cmax of LOXO-338"},{"outcome_type":"secondary","measure":"Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)","time_frame":"Estimated up to 2 years","description":"ORR"},{"outcome_type":"secondary","measure":"Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)","time_frame":"Estimated up to 2 years","description":"PFS"},{"outcome_type":"secondary","measure":"Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)","time_frame":"Estimated up to 2 years","description":"TTP"},{"outcome_type":"secondary","measure":"Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR)","time_frame":"Estimated up to 2 years","description":"DOR"},{"outcome_type":"secondary","measure":"Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC)","time_frame":"Predose up to 24 hours postdose","description":"PK: AUC of LOXO-338 alone and in combination with pirtobrutinib"},{"outcome_type":"secondary","measure":"Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax)","time_frame":"Predose up to 24 hours postdose","description":"PK: Cmax of LOXO-338 alone and in combination with pirtobrutinib"},{"outcome_type":"secondary","measure":"Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR)","time_frame":"Estimated up to 2 years","description":"ORR"},{"outcome_type":"secondary","measure":"Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS)","time_frame":"Estimated up to 2 years","description":"PFS"},{"outcome_type":"secondary","measure":"Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP)","time_frame":"Estimated up to 2 years","description":"TTP"},{"outcome_type":"secondary","measure":"Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR)","time_frame":"Estimated up to 2 years","description":"DOR"}]}
{"nct_id":"NCT05009836","start_date":"2021-08-31","phase":"Phase 3","enrollment":320,"brief_title":"Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC","official_title":"A Multicenter, Randomized, Double-blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Savolitinib + Osimertinib Versus Placebo + Osimertinib as the First Line Therapy for Patients With EGFRm+/MET+ NSCLC","primary_completion_date":"2024-11-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-01-31","last_update":"2021-08-18","description":"A Phase III Clinical Study on Savolitinib Combined with Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic Non-small Cell Lung Cancer","other_id":"2020-504-00CH4","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","intervention_model_description":"This study plans to enroll 320 patients, and eligible patients will be randomized in a ratio of 1:1 into the following treatment groups using central randomization system (IWRS):  Study group: Savolitinib 600 mg or 400 mg QD orally + Osimertinib 80 mg QD orally\r\n Control group: placebo 600 mg or 400 mg QD orally + Osimertinib 80 mg QD orally","sampling_method":"","gender":"All","minimum_age":28,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Fully aware of this study and voluntary to sign the informed consent form, and being\r\n             willing and able to comply with the study procedure;\r\n\r\n          2. Age  18\r\n\r\n          3. In accordance with the Eighth Edition of TNM Staging of Lung Cancer by the\r\n             International Association for the Study of Lung Cancer and American Joint Committee on\r\n             Cancer, and patients with histologically or cytologically confirmed unresectable\r\n             locally advanced (stage B/C), metastatic or recurrent (stage IV) NSCLC who are not\r\n             suitable for radical concurrent chemoradiotherapy;\r\n\r\n          4. Carrying two common EGFR mutations clearly related with the sensitivity to EGFR-TKI\r\n             (i.e., exon 19 deletion, and L858R) and c-MET overexpression\r\n\r\n          5. Having measurable lesions (in accordance with RECIST 1.1 criteria);\r\n\r\n          6. ECOG Performance Status score 0 or 1, or Karnofsky score 80;\r\n\r\n          7. Survival is expected to exceed 12 weeks;\r\n\r\n          8. No any previous systematic antitumor therapy for advanced/metastatic disease;\r\n\r\n          9. adequate bone marrow reserve or organ function\r\n\r\n         10. Female patients of childbearing potential must agree to use effective contraceptive\r\n             methods from screening period to 4 weeks after discontinuation of the study drug 11.\r\n             Male patients whose sexual partners are women of childbearing potential must use\r\n             condoms during sexual intercourse during the study and within 6 months after\r\n             discontinuation of study drug\r\n\r\n        12. Being able to take or swallow the drug orally.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Previous treatment with EGFR inhibitors or MET inhibitors;\r\n\r\n          2. Currently having other malignant tumors, or having other infiltrating malignant tumors\r\n             in the past 5 years\r\n\r\n          3. Antitumor therapy within 2 weeks prior to the start of study treatment, including\r\n             hormone therapy, biotherapy, immunotherapy or the traditional Chinese medicine for\r\n             antitumor indication;\r\n\r\n          4. Having received extensive radiotherapy (including radionuclide therapy, e.g., Sr-89)\r\n             within 4 weeks prior to the start of study treatment or palliative local radiotherapy\r\n             within one week prior to the start of study treatment, or the above adverse reactions\r\n             of radiotherapy did not recover;\r\n\r\n          5. Having received a major surgery within 4 weeks prior to the start of study treatment\r\n             or a minor surgery (except biopsy, and venous catheterization) within one week prior\r\n             to the start of study treatment;\r\n\r\n          6. Currently receiving the potent CYP3A4 inducers or potent CYP1A2 inhibitors within two\r\n             weeks prior to the start of study treatment;\r\n\r\n          7. Having not been sufficiently recovered from the toxicity and/or complication resulting\r\n             from any interventional measure prior to the start of treatment;\r\n\r\n          8. Clinically significant active infection, including but not limited to tuberculosis,\r\n             human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody);\r\n\r\n          9. Active hepatitis B, or active hepatitis C;\r\n\r\n         10. Acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic\r\n             attack;\r\n\r\n         11. Uncontrollable hypertension despite the use of drugs,\r\n\r\n         12. Mean resting corrected QT interval (QTcF) or Any important abnormality in rhythm;\r\n\r\n         13. Patients whose known cancerous thrombus or deep vein thrombosis are stable for 2\r\n             weeks after receiving treatment with low molecular weight heparin (LMWH) or analogues\r\n             with similar efficacy can be enrolled;\r\n\r\n         14. Any important abnormality in rhythm\r\n\r\n         15. Presence of meningeal metastasis, spinal cord compression or active brain metastasis\r\n             prior to the start of study treatment.\r\n\r\n         16. Known allergy to the active or inactive ingredient of Savolitinib or Osimertinib;\r\n\r\n         17. Lack of compliance with participation in this clinical study or inability to comply\r\n             with the limitations and requirements of the study, as judged by investigators;\r\n\r\n         18. Having participated in other drug clinical trials and received the study drug within 3\r\n             weeks prior to the start of study treatment; 19. Known allergy to the active or\r\n             inactive ingredient of Savolitinib or Osimertinib; 20. Previous history of\r\n             interstitial lung diseases, drug-induced interstitial lung diseases, radiation\r\n             pneumonitis requiring glucocorticoid therapy and any active interstitial lung\r\n             diseases; 21. Pregnant and lactating women; 22. Any other disease, metabolic\r\n             abnormality, physical examination abnormality or laboratory examination abnormality,\r\n             certain disease or state, based on which there is a reason to suspect that the subject\r\n             is not suitable for the study drug, or one condition that will affect intepretaton of\r\n             the study results or put the subject at high risk.\r\n      ","sponsor":"Hutchison Medipharma Limited","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Savolitinib","description":"Subjects will receive Savolitinib orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks) until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Subjects will receive placebo orally once per day (QD) + Osimertinib orally QD,21day cycles (every 3 weeks) until disease progression, death, adverse"}],"outcomes":[{"outcome_type":"primary","measure":"PFS","time_frame":"17 months after the last patient enrolled","description":"Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)"},{"outcome_type":"secondary","measure":"Safety and tolerability","time_frame":"17 months after the last patient enrolled","description":"Incidence and nature of treatment emergent adverse events (TEAE), the other safety variables including physical examination, vital signs and laboratory examinations"},{"outcome_type":"secondary","measure":"The objective response rate of the tumor (ORR)","time_frame":"17 months after the last patient enrolled","description":"the incidence of confirmed complete response or partial response"},{"outcome_type":"secondary","measure":"The disease control rate (DCR)","time_frame":"17 months after the last patient enrolled","description":"the incidence of complete response, partial response and stable disease"},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"17 months after the last patient enrolled","description":"the duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"17 months after the last patient enrolled","description":"the time from the date of randomization to the date of death (all causes)"},{"outcome_type":"secondary","measure":"Time to Response (TTR)","time_frame":"17 months after the last patient enrolled","description":"the period from the date of randomization to the date when the criteria for complete response or partial response was first measured (first record shall prevail)."},{"outcome_type":"secondary","measure":"PFS","time_frame":"17 months after the last patient enrolled","description":"Progression-free survival (PFS) using IRC as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)"},{"outcome_type":"secondary","measure":"Development of diagnostic technology","time_frame":"17 months after the last patient enrolled","description":"The residual samples may be used for development of MET Companion Diagnostics (CDx)"}]}
{"nct_id":"NCT05006794","start_date":"2021-08-31","phase":"Phase 1","enrollment":205,"brief_title":"Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Adults With Solid Malignancies","official_title":"A Phase 1a/b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Subjects With Solid Malignancies","primary_completion_date":"2027-05-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2028-05-31","last_update":"2021-08-25","description":"The primary objective of Part A of this study is to define the maximum tolerated dose (MTD) or maximum administered dose of GS-9716 as monotherapy in advanced solid malignancies and to characterize the safety, and tolerability of GS-9716 monotherapy. The primary objectives of Parts B and C of this study are: To characterize the safety, tolerability, and to define MTD and/or recommended Phase 2 dose (RP2D) of GS-9716 in combination with either docetaxel or sacituzumab govitecan-hziy in adults with metastatic non-squamous non-small cell lung cancer (NSCLC) following treatment for metastatic disease, including an immune checkpoint inhibitor and a single line of platinum containing chemotherapy (for Cohorts B1, B2, C1, and C2) and in adults with metastatic triple-negative breast cancer (TNBC) following a single line of therapy for metastatic disease (for Cohorts B3, B4, C3, and C4); To characterize the safety, tolerability, and to define MTD and/or the RP2D of GS-9716 in combination with gemcitabine and docetaxel in metastatic soft tissue sarcomas (mSTS) with nonspecific histologies previously untreated for metastatic disease (for Cohorts B5 and C5).","other_id":"GS-US-467-5643","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n        Part A: GS-9716 Monotherapy\r\n\r\n          -  Histologically or cytologically confirmed epithelial cancer, stage IV (metastatic)\r\n             disease or locally advanced and unresectable (mixed histologies not permitted):\r\n\r\n               -  Breast cancer\r\n\r\n               -  Castrate-resistant prostate cancer not on hormonal androgen deprivation therapy\r\n\r\n               -  Cervical cancer\r\n\r\n               -  Colorectal cancer\r\n\r\n               -  Endometrial cancer\r\n\r\n               -  Epithelial ovarian cancer\r\n\r\n               -  Esophageal cancer\r\n\r\n               -  Follicular thyroid cancer\r\n\r\n               -  Gastric or gastroesophageal junction adenocarcinoma\r\n\r\n               -  Head and neck cancers- squamous cell carcinoma\r\n\r\n               -  Hepatocellular carcinoma\r\n\r\n               -  NSCLC\r\n\r\n               -  Renal cell cancer (clear cell)\r\n\r\n               -  Small-cell lung cancer\r\n\r\n               -  Urothelial cancer\r\n\r\n          -  Progressed after at least 1 prior standard therapeutic regimen, or for whom no\r\n             standard therapy is available, standard therapy has failed, or for whom standard of\r\n             care therapy is contraindicated\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per\r\n             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as described in\r\n             protocol\r\n\r\n          -  Adequate hematology, renal and hepatic function as described in the protocol\r\n\r\n          -  All toxicity at screening  Grade 1, including peripheral neuropathy and excluding\r\n             alopecia of any grade, well-controlled endocrine toxicities from prior immune\r\n             checkpoint inhibitor therapy  Grade 2, and chronic electrolyte abnormalities\r\n             requiring supplementation  Grade 2\r\n\r\n          -  Left ventricular ejection fraction (LVEF)  50% acquisition scan (MUGA) may be\r\n             acceptable per discussion with the medical monitor\r\n\r\n          -  Tissue criteria: Individuals must have available, sufficient, and adequate\r\n             formalin-fixed tumor tissue sample or must agree to have a biopsy taken prior to\r\n             entering the study to provide adequate tissue. Core needle or excisional biopsy or\r\n             resected tissue is required.\r\n\r\n        Part B and Part C: GS-9716 in Combination with Anticancer Therapies (All Cohorts)\r\n\r\n          -  ECOG performance status of 0 or 1\r\n\r\n          -  Adequate hematology, renal and hepatic function as described in the protocol\r\n\r\n          -  Otherwise, all toxicity at screening entry  Grade 1, including peripheral neuropathy\r\n             and excluding alopecia of any grade, well-controlled endocrine toxicities from prior\r\n             immune checkpoint inhibitor therapy  Grade 2, and chronic electrolyte abnormalities\r\n             requiring supplementation  Grade 2\r\n\r\n          -  LVEF  50%, as well as no clinically significant pericardial effusion\r\n\r\n          -  Tissue criteria:\r\n\r\n               -  TNBC cohorts B3, C3, B4, C4: Individuals must have a tumor lesion that a\r\n                  mandatory pretreatment biopsy can be obtained from. Core needle, or excisional\r\n                  biopsy, or resected tissue is required. Fine needle aspirates and bone biopsies\r\n                  are not acceptable\r\n\r\n               -  Cohorts B1, C1, B2, C2, B5, C5: Individuals must have available, sufficient, and\r\n                  adequate formalin-fixed tumor tissue sample or must agree to have a biopsy taken\r\n                  prior to entering the study to provide adequate tissue. Core needle or excisional\r\n                  biopsy or resected tissue is required.\r\n\r\n        Cohorts B1, B2, C1, and C2:\r\n\r\n          -  Histologically or cytologically confirmed unresectable metastatic or locally advanced,\r\n             non-squamous NSCLC following treatment for metastatic disease including an immune\r\n             checkpoint inhibitor and a single line of platinum-containing chemotherapy\r\n\r\n          -  Individuals with bone metastases currently receiving bisphosphonates for palliation\r\n             will be eligible providing informed consent can be given and that other qualifying\r\n             sites of measurable disease are present.\r\n\r\n        Cohorts B3, B4, C3, and C4:\r\n\r\n          -  Histologically or cytologically confirmed TNBC based on the most recent analyzed\r\n             biopsy or other pathology specimen. Triple-negative status for TNBC will be defined by\r\n             American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)\r\n             guidelines (US sites) or their equivalent (ex-US sites)\r\n\r\n          -  Unresectable locally advanced or metastatic disease following only 1 prior standard\r\n             therapeutic regimen for TNBC. Individuals who have received 2 or more prior systemic\r\n             therapies are not eligible\r\n\r\n          -  Individuals with bone metastases currently receiving bisphosphonates for palliation\r\n\r\n          -  Individuals with stable, treated brain metastases will be eligible.\r\n\r\n        Cohorts B5 and C5:\r\n\r\n          -  Histologically proven soft tissue sarcoma (except the following histologies:\r\n             gastrointestinal stromal tumors [GIST], Kaposi's sarcoma, mesotheliomas) which has\r\n             been previously untreated for metastatic disease.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Prior treatment with any myeloid cell leukemia 1 (MCL1) inhibitor\r\n\r\n          -  Treatment with any high dose systemic corticosteroids within 2 weeks of the first dose\r\n             of GS-9716. However, low dose corticosteroids  10 mg prednisone or equivalent daily\r\n             is permitted\r\n\r\n          -  Prior radiotherapy (or other nonsystemic therapy) within 2 weeks prior to dosing with\r\n             GS-9716\r\n\r\n          -  Women who are pregnant or lactating\r\n\r\n          -  Individuals with brain metastases may be enrolled only if treated, nonprogressive, and\r\n             asymptomatic as well as off high dose steroids (> 10 mg prednisone or equivalent) for\r\n             at least 4 weeks prior to dosing with GS-9716\r\n\r\n          -  History of leptomeningeal disease\r\n\r\n          -  Individuals with active  Grade 2 nausea or vomiting, and/or signs of intestinal\r\n             obstruction\r\n\r\n          -  Known active or chronic hepatitis B or C infection or HIV infection or HIV positive\r\n\r\n          -  Known history of unstable angina, myocardial infarction (MI), cardiac angioplasty or\r\n             stenting, or clinically significant cardiac disease would include QTc interval > 450\r\n             ms for males and > 470 ms for females\r\n\r\n          -  Known history of clinically significant active chronic obstructive pulmonary disease\r\n             (COPD), or other moderate to severe chronic respiratory illness present within 6\r\n             months prior to dosing with GS-9716\r\n\r\n          -  Known history of clinically significant pulmonary interstitial lung disease, active\r\n             interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,\r\n             bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or\r\n             evidence of active pneumonitis on screening chest CT scan\r\n\r\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent\r\n             drainage procedures (more frequently than once monthly)\r\n\r\n          -  Prior history of clinically significant bleeding, intestinal obstruction, or\r\n             gastrointestinal (GI) perforation within 6 months of initiation of study treatment\r\n\r\n          -  Infection requiring intravenous anti-infective use within 2 weeks prior to dosing with\r\n             GS-9716\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  History of uncured coexisting cancer, not including uncured basal cell carcinoma,\r\n             cervical cancer in situ, or superficial bladder cancer.\r\n\r\n        Cohorts B1, B3, B5, C1, C3, and C5:\r\n\r\n          -  Bilirubin > upper limit of normal (ULN).\r\n\r\n        Cohorts B1, B2, C1, and C2:\r\n\r\n          -  More than 1 prior chemotherapy regimen for metastatic non-squamous NSCLC; however,\r\n             this would not exclude those who received frontline immune checkpoint inhibitor as\r\n             monotherapy followed by a platinum-containing chemotherapeutic regimen in the second\r\n             line\r\n\r\n          -  Non-squamous NSCLC with targetable mutations (e.g., anaplastic lymphoma kinase [ALK],\r\n             epidermal growth factor receptor [EGFR], proto-oncogene tyrosine-protein kinase ROS\r\n             [ROS1], v-RAF murine sarcoma viral oncogene homolog B [BRAF]) for which approved\r\n             therapies are available\r\n\r\n          -  Cohorts B2 and C2 only: Prior therapy with sacituzumab govitecan-hziy or a\r\n             topoisomerase 1 inhibitor or agents targeting Trop-2.\r\n\r\n        Cohorts B3, B4, C3, and C4:\r\n\r\n          -  More than 1 prior chemotherapy regimen for metastatic TNBC\r\n\r\n          -  Cohorts B4 and C4 only: Prior treatment with sacituzumab govitecan-hziy or a\r\n             topoisomerase 1 inhibitor or agents targeting Trop-2.\r\n\r\n        Cohorts B5 and C5:\r\n\r\n          -  Any previous treatment for metastatic disease\r\n\r\n          -  Soft tissue sarcomas with the following histologies: GIST, Kaposi's sarcoma, or\r\n             mesotheliomas.\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"Gilead Sciences","sponsor_type":"Industry","conditions":"Solid Malignancies","interventions":[{"intervention_type":"Drug","name":"Drug: GS-9716","description":"Tablet(s) administered orally"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Sacituzumab Govitecan-hziy","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Administered intravenously"}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)","time_frame":"First dose date up to 21 days"},{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0","time_frame":"First dose date up to last dose date (Maximum: 105 weeks) plus 30 days"},{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0","time_frame":"First dose date up to last dose date (Maximum: 105 weeks) plus 30 days"},{"outcome_type":"secondary","measure":"Maximum Observed Concentration (Cmax) for GS-9716","time_frame":"Approximately 2 years"},{"outcome_type":"secondary","measure":"Time to Maximum Observed Concentration (Tmax) for GS-9716","time_frame":"Approximately 2 years"},{"outcome_type":"secondary","measure":"Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) for GS-9716","time_frame":"Approximately 2 years"},{"outcome_type":"secondary","measure":"Parts B and C: Objective Response Rate (ORR)","time_frame":"Up to 105 weeks","description":"ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Parts B and C: Confirmed ORR","time_frame":"Up to 105 weeks","description":"Confirmed ORR is defined as the percentage of participants who achieve a confirmed CR or confirmed PR by RECIST version 1.1."},{"outcome_type":"secondary","measure":"Parts B and C: Disease Control Rate (DCR)","time_frame":"Up to 105 weeks","description":"DCR is defined as the percentage of participants who achieve a CR, PR, or stable disease (SD) as assessed by RECIST version 1.1."},{"outcome_type":"secondary","measure":"Parts B and C: Progression-Free Survival (PFS)","time_frame":"First dose date to PD or death, whichever occurs first (up to 39 months)","description":"PFS is defined as the interval from the first dose of GS-9716 to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Parts B and C: Time to Response (TTR)","time_frame":"First dose date to the first documentation of CR or PR (up to 105 weeks)","description":"TTR is defined as the time from first dose of GS-9716 to the first documentation of CR or PR."},{"outcome_type":"secondary","measure":"Parts B and C: Duration of Response (DOR)","time_frame":"From first documentation of CR or PR to PD or death, whichever occurs first (up to 37 months)","description":"DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause."},{"outcome_type":"secondary","measure":"Parts B and C: Overall Survival (OS)","time_frame":"First dose date to death (up to 39 months)","description":"OS is defined as the time from date of first dose of GS-9716 to death from any cause."}]}
{"nct_id":"NCT05004350","start_date":"2021-08-31","phase":"Phase 2","enrollment":103,"brief_title":"A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.","official_title":"A Multicenter, Randomized, Open-label, 2-arm, Phase II Study With a Safety lead-in Phase Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.","primary_completion_date":"2024-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-30","last_update":"2021-08-13","description":"Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.","other_id":"W00090GE202","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria for Molecular Prescreening:\r\n\r\n        The following inclusion criteria must be met for a participant to be eligible to undergo\r\n        molecular tumor prescreening:\r\n\r\n          -  Chinese male or female participant with age 18 years at the time of informed consent.\r\n\r\n          -  Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic.\r\n\r\n          -  Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat\r\n             Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma\r\n             Viral Oncogene Homologue Wild Type(RAS wt) status).\r\n\r\n          -  Able to provide a sufficient amount of representative tumor specimen for central\r\n             prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF)\r\n             mutation status and also retrospective RAS wt status and Microsatellite Instability\r\n             (MSI) testing.\r\n\r\n        Inclusion Criteria for Treatment Period:\r\n\r\n        The following inclusion criteria must be met for a participant to be eligible for this\r\n        study:\r\n\r\n          -  Chinese male or female participant with age 18 years at time of informed consent.\r\n\r\n          -  Histologically or cytologically confirmed CRC that is metastatic and unresectable at\r\n             time of study entry (i.e. not suitable for complete surgical resection at screening).\r\n\r\n          -  Presence of a BRAF V600E mutation in tumor tissue previously determined by a local\r\n             assay at any time before screening or by the central laboratory.\r\n\r\n        NOTE: Other protocol defined Inclusion criteria may apply\r\n\r\n        Exclusion Criteria for Molecular Prescreening:\r\n\r\n        Participants meeting any of the following criteria are not eligible to undergo molecular\r\n        tumor prescreening:\r\n\r\n          -  Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment\r\n\r\n          -  More than two prior regimens in the metastatic setting.\r\n\r\n          -  Known contraindication to receive cetuximab or irinotecan at the planned dose\r\n             according to the most recent cetuximab and irinotecan local label.\r\n\r\n          -  Known history of Gilbert's syndrome or is known to have any of the following\r\n             genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28\r\n             or UGT1A1*6/*28.\r\n\r\n          -  Leptomeningeal disease.\r\n\r\n        Exclusion Criteria for Treatment Period:\r\n\r\n          -  Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF)\r\n             inhibitor, cetuximab, panitumumab or other EGFR inhibitors.\r\n\r\n          -  Symptomatic brain metastasis.\r\n\r\n          -  Leptomeningeal disease.\r\n\r\n          -  Use of any herbal medications/supplements or any medications or foods that are\r\n             moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 1 week before\r\n             the start of study intervention.\r\n\r\n          -  Known history of acute or chronic pancreatitis within 6 months before the start of\r\n             study intervention.\r\n\r\n        NOTE: Other protocol defined Exclusion criteria may apply\r\n      ","sponsor":"Pierre Fabre Medicament","sponsor_type":"Industry","conditions":"BRAF V600E|Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Encorafenib","description":"oral capsule"},{"intervention_type":"Drug","name":"Drug: Cetuximab","description":"intravenous infusion"},{"intervention_type":"Drug","name":"Drug: FOLFIRI","description":"Combination of:\r\nirinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion"}],"outcomes":[{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"primary","measure":"Safety Lead-in Phase: Incidence of Dose Limiting Toxicities (DLTs) during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI)","time_frame":"Day 1 to Day 28"},{"outcome_type":"primary","measure":"Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to treatment received) Independent Central Review (BICR)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1., or death due to any cause"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03","time_frame":"Informed consent through to study completion, approximately from 18 to 35 months"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported."},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Weight (kg) increase from baseline of ≥ 10%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: Systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; Weight: ≥ 20% decrease from baseline; Body temperature [°C]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported."},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms) : increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. Heart rate (beats/min) : increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported."},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above."},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of development of of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations","time_frame":"Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months","description":"This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit."},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Performance status assessment using the Eastern Co-operative Oncology Group (ECOG) performance status scale","time_frame":"Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months","description":"Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events (AEs)","time_frame":"Day 1 until end of treatment, approximately 1 year"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Plasma concentrations of encorafenib","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Serum concentrations of cetuximab","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Objective response rate (ORR)","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"Objective response rate (ORR) defined as the proportion of participants with a best overall best response of either complete response (CR) or partial response (PR) as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1"},{"outcome_type":"secondary","measure":"Safety Lead-in Phase: Duration of Response (DOR) (months); defined for responders complete response (CR) or partial response (PR) only, is duration of time from the date of the first documented response to the earliest date of disease progression","time_frame":"Day 1 through to study completion, approximately from 18 to 35 months","description":"Duration of response, defined as the time from first documented response (complete response or partial response) to the earliest date of disease progression as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death due to underlying disease."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Progression-free survival (PFS)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Progression-free survival defined as the interval of time between the date of randomization to the earliest date of disease progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Overall Response Rate (ORR)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Overall response rate (for confirmed and unconfirmed responses) defined as the proportion of participants with a confirmed (resp. unconfirmed) best overall response of either complete response or partial response, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Duration of Response (DOR)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Disease control rate (DCR)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Disease control rate (DCR), defined as the proportion of participants with a best overall response of either complete response, partial response or stable disease (SD), as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Time to Response (TTR)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Time to Response (for confirmed and unconfirmed responses) is defined as the time between date of randomization until first documented response of complete response (CR) or partial response (PR)."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Overall Survival (OS)","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Overall survival is defined as time from randomization until date of death due to any cause"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Type and severity of adverse events (AEs) and serious adverse events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03","time_frame":"Informed consent date through to study completion, approximately from 12 to 29 months"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in vital signs from baseline.","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Weight (kg) increase from baseline of ≥ 10%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: Systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; Weight: ≥ 20% decrease from baseline; Body temperature [°C]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported."},{"outcome_type":"secondary","measure":"Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes to electrocardiogram evaluations from baseline","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms; Heart rate (beats/min): increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above."},{"outcome_type":"secondary","measure":"Randomized Phase 2: Incidence of development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit."},{"outcome_type":"secondary","measure":"Randomized Phase 2: To determine the performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale.","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death"},{"outcome_type":"secondary","measure":"Randomized Phase 2: To determine if there is any change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire scores","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"EORTC QLQ-C30 consist of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale. Each scale in the questionnaire will be scored (0 to 100). High scores represents a high health/quality of life"},{"outcome_type":"secondary","measure":"Randomized Phase 2: To determine if there is any change from baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire scores.","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system has five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each is rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that describes the participant's health state."},{"outcome_type":"secondary","measure":"Randomized Phase 2: To determine if there is any change from baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) questionnaire scores","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"FACT-C is a validated quality of life questionnaire for patient reported outcome assessment. FACT-C consists of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale. Higher score reflects a better quality of life."},{"outcome_type":"secondary","measure":"Randomized Phase 2: To determine if there is any changes in the Patient Global Impression of Change (PGIC) questionnaire scores.","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months","description":"PGIC will ask participants to evaluate their CRC symptoms since starting study intervention according to a seven-point verbal rating scale (VRS): 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Plasma concentrations of encorafenib","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Serum concentrations of cetuximab","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants","time_frame":"Day 1 of Cycles 1 and 2; Each cycle = 28 days"},{"outcome_type":"secondary","measure":"Randomized Phase 2: Population pharmacokinetic (PK) analysis using the ARRAY 818 302 study PK data","time_frame":"Day 1 through to study completion, approximately from 12 to 29 months"},{"outcome_type":"other","measure":"Randomized Phase 2: Changes from baseline in blood Carcinoembryonic Antigen (CEA) and Cancer Antigen 19-9 (CA19-9) at the beginning of each cycle and at the end of treatment","time_frame":"Screening (Day -28 to -1) through to study completion, approximately from 12 to 29 months"},{"outcome_type":"other","measure":"Randomized Phase 2: Microsatellite Instability (MSI) status in Formalin-fixed and Paraffin Embedded (FFPE) samples using established Polymerase Chain Reaction (PCR) assays in tumor sample versus germline control at screening","time_frame":"Screening (Day -28 to Day -1)"}]}
{"nct_id":"NCT05002127","start_date":"2021-08-31","phase":"Phase 2/Phase 3","enrollment":450,"brief_title":"A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06)","official_title":"A Phase 2/3 Study of Evorpacept (ALX148) in Patients With Advanced HER2-Overexpressing Gastric/Gastroesophageal Junction Adenocarcinoma (ASPEN-06)","primary_completion_date":"2026-07-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2028-08-31","last_update":"2021-08-27","description":"A Phase 2/3 Study of Evorpacept (ALX148) in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Patients With Advanced HER2-overexpressing gastric/GEJ adenocarcinoma.","other_id":"AT148006","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  HER2-overexpressing advanced or metastatic gastric or gastroesophageal junction (GEJ)\r\n             adenocarcinoma that has progressed on or after a prior HER2-directed agent and\r\n             fluoropyrimidine- or platinum-containing chemotherapy (2nd-line or 3rd-line)\r\n\r\n          -  Adequate Bone Marrow Function.\r\n\r\n          -  Adequate Renal & Liver Function.\r\n\r\n          -  Adequate Performance Status\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Patients with known symptomatic CNS metastases or leptomeningeal disease requiring\r\n             steroids.\r\n\r\n          -  Prior treatment with any anti-CD47 or anti-SIRP agent.\r\n\r\n          -  Prior treatment with ramucirumab.\r\n      ","sponsor":"ALX Oncology Inc.","sponsor_type":"Industry","conditions":"Gastric Cancer|Gastroesophageal Junction Adenocarcinoma|Gastric Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Evorpacept (ALX148)","description":"IV Q2W"},{"intervention_type":"Drug","name":"Drug: Trastuzumab","description":"IV Q2W"},{"intervention_type":"Drug","name":"Drug: Ramucirumab","description":"IV Q2W"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"IV Days 1, 8, and 15 of a 28-day cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Phase 2","time_frame":"Last randomized patient on study at least 16 weeks","description":"Percentage of patients with objective response per RECIST 1.1"},{"outcome_type":"primary","measure":"Phase 3","time_frame":"From the date of randomization to the date of death (due to any cause), up to 36 months postdose","description":"Overall Survival"}]}
{"nct_id":"NCT04985136","start_date":"2021-08-31","phase":"Phase 3","enrollment":482,"brief_title":"A Study of Camrelizumab Combined With Rivoceranib Mesylate Versus Investigator's Choice of Regimen in Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)","official_title":"A Randomized, Open-Label, Controlled, International Multi-Center Phase III Clinical Study of Camrelizumab Combined With Rivoceranib (Apatinib) Mesylate Versus Investigator's Choice of Regimen in Treatment of Patients With Hepatocellular Carcinoma (HCC) Who Have Been Treated With Immune Checkpoint Inhibitors (ICIs)","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-03-30","last_update":"2021-08-02","description":"This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of Camrelizumab Combined with Rivoceranib Mesylate versus Investigator's Choice of Regimen in Treatment of Patients with Hepatocellular Carcinoma (HCC)","other_id":"SHR-1210-III-330","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"RandomizedOpenControlled, International Multi-Center","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Subject must participate voluntarily and sign the informed consent form;\r\n\r\n          2. Aged  18 years old, male or female;\r\n\r\n          3. Histopathologically confirmed hepatocellular carcinoma;\r\n\r\n          4. Has PD on treatment with prior anti-PD-1/PD-L1/CTLA-4 monoclonal antibody (mAb)\r\n             administered either as monotherapy or as combination therapy.\r\n\r\n          5. No more than 2 lines of previous system treatment;\r\n\r\n          6. Be able to provide fresh or archived tumor tissue samples;\r\n\r\n          7. Patient with at least one measurable lesion (for Stage I);\r\n\r\n          8. Barcelona clinic liver cancer: Stage B or C;\r\n\r\n          9. Child-Pugh score:  7;\r\n\r\n         10. ECOG PS score of 0-1;\r\n\r\n         11. Life expectancy of  12 weeks;\r\n\r\n         12. Adequate organ function\r\n\r\n         13. Must take one medically approved contraceptive measure\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Patients with any active, known or suspected autoimmune disorder;\r\n\r\n          2. Patients who have used corticosteroids or other immunosuppressive agents for systemic\r\n             treatment within 1 month prior to randomization;\r\n\r\n          3. With known severe allergic reactions to any other monoclonal antibodies;\r\n\r\n          4. Received previous camrelizumab or rivoceranib mesylate treatment;\r\n\r\n          5. Patients who discontinued ICIs treatment due to immune-related toxicity;\r\n\r\n          6. Patients with known CNS metastasis or hepatic encephalopathy;\r\n\r\n          7. Patients with liver tumor burden greater than 50% of total liver in volume, or\r\n             patients who have previously undergone liver transplantation;;\r\n\r\n          8. Patients with symptomatic ascites or pleural effusion requiring paracentesis and\r\n             drainage, or patients who have undergone ascites or pleural effusion drainage within 2\r\n             weeks before randomization;\r\n\r\n          9. Patients with other malignancies currently or within the past 5 years;\r\n\r\n         10. Patients with hypertension which cannot be well controlled by antihypertensives;\r\n             history of hypertensive crisis or hypertensive encephalopathy;\r\n\r\n         11. Uncontrolled cardiac diseases or symptoms\r\n\r\n         12. Known hereditary or acquired bleeding disorders;\r\n\r\n         13. Clinically significant bleeding symptoms or clear bleeding tendency;\r\n\r\n         14. Patients with gastrointestinal perforation or gastrointestinal fistula;\r\n\r\n         15. Patients with significant vascular invasions with a high possibility of fatal\r\n             bleeding;\r\n\r\n         16. Patients with important arterial/venous thrombosis;\r\n\r\n         17. Patients experiencing toxicity caused by previous anti-tumor therapy that has not\r\n             recovered to Grade  1;\r\n\r\n         18. Patients with active infection;\r\n\r\n         19. Patients with congenital or acquired immune deficiency;\r\n\r\n         20. Patients who received live vaccines within 28 days prior to randomization, or are\r\n             expect to be vaccinated during the treatment period;\r\n\r\n         21. Patients with other potential factors that may affect the study results.\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Hepatocellular Carcinoma (HCC)","interventions":[{"intervention_type":"Drug","name":"Drug: camrelizumabRivoceranib","description":"Camrelizumab at 200 mg via intravenous administration (IV), once every 2 weeks (Q2W), in combination with 250 mg of rivoceranib mesylate, oral administration, once a day (QD)"},{"intervention_type":"Drug","name":"Drug: Rivoceranib","description":"Rivoceranib mesylate (750 mg, QD, po)"},{"intervention_type":"Drug","name":"Drug: Sorafenib","description":"Sorafenib tosylate (400 mg, twice a day (BID), po)"},{"intervention_type":"Drug","name":"Drug: Regorafenib","description":"Regorafenib (160 mg, administer for 21 days then stop for 7 days, po)"}],"outcomes":[{"outcome_type":"primary","measure":"Stage I：Objective Response Rate（ORR）","time_frame":"2.5 years"},{"outcome_type":"primary","measure":"Stage II：Overall survival （OS）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Stage I：Overall survival （OS）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Adverse Events（AEs）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Stage II：Objective Response Rate（ORR）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Disease Control Rate（DCR）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Duration of Response（DoR）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Progression-Free-Survival （PFS）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"time to progression （TTP）","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) Ctrough of camrelizumab","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) Ctrough of Apatinib","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Proportion of anti- camrelizumab antibody (ADA)","time_frame":"2.5 years"},{"outcome_type":"secondary","measure":"Proportion of neutralizing antibody (Nab)","time_frame":"2.5 years"}]}
{"nct_id":"NCT04984668","start_date":"2021-08-31","phase":"Phase 1/Phase 2","enrollment":216,"brief_title":"A Phase Ib/II Study of GT90001 Combined With KN046 in Solid Tumors","official_title":"A Phase Ib/II, Multicenter Study of GT90001 in Combination With KN046 in Patients With Advanced or Refractory Solid Tumors","primary_completion_date":"2024-09-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-09-30","last_update":"2021-07-30","description":"Phase Ib is a dose De-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of GT90001 in combination with KN046 in subjects with advanced or refractory hepatocellular carcinoma (HCC), gastric carcinoma (GC) and gastroesophageal junction (GEJ) adenocarcinoma, urothelial carcinoma (UC) and esophageal square cell carcinoma (ESCC). Phase II is to investigate anti-tumor efficacy of GT90001 in combination with KN046 at RP2D in subjects with specific types of tumors. A Simon two-stage design is planned for each indication in order to minimize the number of treated participants if there is minimal efficacy activity in that indication.","other_id":"GT90001-TW-2001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion criteria:\r\n\r\n        General\r\n\r\n          1. Age 18 years, or  minimum legal age to attend a clinical study.\r\n\r\n          2. Be willing and able to provide written informed consent/assent for the trial.\r\n\r\n          3. Ability to comply with requirements of the protocol, as assessed by the investigator.\r\n\r\n          4. Disease-Specific Inclusion Criteria All subjects must have unresectable locally\r\n             advanced or metastatic tumors that have histologic or cytological documentation\r\n             confirmed.\r\n\r\n               -  Phase Ib: subjects with advanced HCC, GC or GEJ adenocarcinoma, Urothelial\r\n                  transitional cell Carcinoma and Esophagus Carcinoma who have progressed despite\r\n                  standard therapies, are intolerant of standard therapy, or for whom no standard\r\n                  therapy exists;\r\n\r\n               -  Phase II: subjects with tumor of specific types:\r\n\r\n        Cohort# Indication Inclusion criteria\r\n\r\n          1. HCC, 2L Unresectable histologic confirmed primary hepatocellular carcinoma. Subjects\r\n             with radiological diagnosis may also be enrolled in the study.\r\n\r\n             Documented radiographic or clinical disease progression during or after 1st line\r\n             therapy, including Sorafenib, Lenvatinib and Atezolizumab plus Bevacizumab and other\r\n             1st line standard care per local clinical practice.\r\n\r\n             Patient has a Child-Pugh score of 5 or 6 points and no encephalopathy and/or\r\n             clinically apparent ascites. (Note: Child-Pugh score should be evaluated within 7 days\r\n             of first dose of study drug)\r\n\r\n          2. GC or GEJ adenocarcinoma, 3L Unresectable locally advanced or metastatic GC or GEJ\r\n             carcinoma and have histologically confirmed adenocarcinoma.\r\n\r\n             At least 50% subjects with PD-L1 expression (CPS) on  1% will be enrolled in this\r\n             cohort.\r\n\r\n             Has experienced documented objective radiographic or clinical disease progression\r\n             during or after standard first line Platinum- and fluoropyrimidine-based two or three\r\n             cytotoxic drug chemotherapy and second line NCCN recommended treatment regimen therapy\r\n             or other 1st and 2nd line standard care per local clinical practice. (Note: subjects\r\n             with discontinuation due to AEs prior to disease progression are not considered as\r\n             treatment failure unless disease progression is confirmed by documentation.) Disease\r\n             progression during or within 6 months following the last dose of adjuvant or\r\n             neo-adjuvant therapy will be considered as 1st line failure.\r\n\r\n          3. UC, 2L Histologically or cytologically confirmed urothelial carcinoma of the renal\r\n             pelvis, ureter, bladder, or urethra that showed predominantly transitional-cell\r\n             features Has experienced documented progression or recurrence after at least the 1st\r\n             line platinum-based chemotherapy or recurrence within 12 months after the receipt of\r\n             platinum-based adjuvant or neoadjuvant therapy for localized muscle-invasive disease.\r\n\r\n        Note: Primary chemoradiation for unresectable muscle-invasive bladder cancer with the aim\r\n        of bladder preservation will not be considered a prior line of systemic therapy for the\r\n        purposes of determining study eligibility.\r\n\r\n        4 ESCC 2L Histologically confirmed, unresectable squamous cell carcinoma of the esophagus.\r\n\r\n        The primary tumor must originate in the esophagus. Tumors that involve the GE junction must\r\n        meet Sievert Type 1 criteria, 1-5 cm above the EGJ. For the purposes of this protocol, this\r\n        will be interpreted as: greater than 50% of the tumor must be above the GE junction.\r\n\r\n        Patients must have received at least one prior therapy for unresectable disease. Patients\r\n        with recurrence within 6 months of completion of neoadjuvant or adjuvant therapy may be\r\n        considered as having received one prior therapy for unresectable disease.\r\n\r\n        5. Patient must have at least one measurable lesion by CT or MRI per RECIST 1.1. Tumor\r\n        lesions situated in a previously irradiated area are considered measurable if progression\r\n        has been demonstrated in such lesions. Loco-regional treated lesion cannot be selected as a\r\n        target lesion.\r\n\r\n        6. ECOG performance status score of 0 or 1. 7. Life expectancy  12 weeks. 8. At screening,\r\n        patients in Phase II part must agree to provide archival tumor tissue, if available, for\r\n        biomarker testing. When archival tissue is not available, it is optional for patients to\r\n        undergo fresh biopsy judged medically safe by the investigator.\r\n\r\n          1. Archival tumor tissue can be formalin-fixed paraffin embedded (FFPE) tissue block\r\n             (preferably collected within 12 months before the first dose) or at least 5 freshly\r\n             sectioned unstained slides. Tissue block is preferred over unstained slides.\r\n\r\n          2. Acceptable tissue sample include core needle punctured, resected or incisional biopsy,\r\n             or surgical sample. (Note: Fine needle aspirational cytology (FNAC) sample is not\r\n             acceptable. Tumor tissue from bone metastases is not evaluable for determination of\r\n             PD-L1 expression and is therefore also not acceptable.) 9. Any toxic effects of prior\r\n             anti-cancer therapy or surgical procedures resolved to baseline severity or NCI-CTCAE\r\n             version 5 Grade  1 (except alopecia or other toxicities not considered a safety risk\r\n             for the patient at investigator's discretion).\r\n\r\n        Clinical Laboratory Inclusion Criteria\r\n\r\n        10. Subject must have adequate organ function as indicated by the following laboratory\r\n        values [had not received blood transfusion, erythropoietin (EPO), granulocyte colony\r\n        stimulating factor (G-CSF) or other relevant medical support within 14 days before the\r\n        administration of the investigational product]:\r\n\r\n        Absolute neutrophil count (ANC)  1.5109/L Platelets  100 109/L ( 60 109/L for HCC\r\n        subjects) Hemoglobin  9 g/dL or  5.6 mmol/L Serum creatinine  1.5  upper limit of\r\n        normal (ULN); AND calculated creatinine clearance (CrCL) > 50 mL/min (Cockcroft-Gault\r\n        formula) Total bilirubin  1.5  ULN OR 2.5  ULN for HCC OR  2  ULN in case of known\r\n        Gilbert disease AST (SGOT) and ALT (SGPT)  2.5  ULN OR  5  ULN for HCC patients or\r\n        patients with liver metastases Serum albumin  28 g/L (no albumin transfusion within 14\r\n        days) International Normalized Ratio (INR) or Prothrombin Time (PT)  1.5  ULN Activated\r\n        Partial Thromboplastin Time (aPTT)  1.5  ULN\r\n\r\n        11. Subjects with hepatitis B virus (HBV) infection must have HBV DNA < 2000 IU/mL at\r\n        screening.\r\n\r\n        Subjects with positive HBsAg and/or positive HBV DNA that requires anti-HBV treatment for\r\n        at least 2 weeks prior to the first dose of study drugs and are willing to continue\r\n        receiving antiviral treatment.\r\n\r\n        12. Women of childbearing potential (WOCBP) must have a negative pregnancy test result.\r\n        Either Female or male patients must agree to use adequate contraceptive measures from\r\n        signing informed consent and for 180 days after last investigational product\r\n        administration, except for a patient with documented surgical sterilization or a\r\n        postmenopausal female.\r\n\r\n        Exclusion criteria:\r\n\r\n        Target Disease Exceptions 1. For phase II expansion study, patients with specific types of\r\n        tumors are also required to be excluded by following criteria: Cohort # Indication\r\n        Exclusion criteria\r\n\r\n          1. HCC, 2L Fibrolamellar, sarcomatoid and mixed hepatocellular/ cholangiocarcinoma\r\n             histology Any history of hepatic encephalopathy Active coinfection with both hepatitis\r\n             B and C, as evidenced by positivity of both HBV DNA and HCV RNA.\r\n\r\n          2. GC or GEJ adenocarcinoma, 3L Has squamous cell, undifferentiated, mixed or other\r\n             histology other than gastric adenocarcinoma.\r\n\r\n          3. UC, 2L Has locally advanced UC is suitable for local therapy administration with\r\n             curative intention (as determined by local investigators)\r\n\r\n          4. ESCC 2L Has locally advanced esophageal carcinoma that is resectable or potentially\r\n             curable with radiation therapy (as determined by local investigator) Histologically\r\n             confirmed, unresectable adenocarcinoma, undifferentiated carcinomas or adenosquamous\r\n             carcinomas of the esophagus.\r\n\r\n        Tumors that involve the GE junction Sievert Type 2 and Sievert Type 3, or greater than 50%\r\n        of the tumor below the GE junction as determined by endoscopy.\r\n\r\n        Medical History and Concurrent Diseases\r\n\r\n        2. Prior malignancy active within the previous 3 years except for locally curable cancers\r\n        that have been apparently cured, such as basal or squamous cell skin cancer, superficial\r\n        bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.\r\n\r\n          1. Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis. Patients with previously treated brain metastases may participate provided\r\n             they are stable (without evidence of progression by imaging for at least 4 weeks prior\r\n             to the first dose of investigational product and any neurologic symptoms have returned\r\n             to baseline), have no evidence of new or enlarging brain metastases, and are not using\r\n             steroids for at least 7 days prior to study treatment.\r\n\r\n          2. Any prior (within 1 year) or current clinically significant ascites as measured by\r\n             physical examination and that requires active paracentesis for control.\r\n\r\n          3. Patients with active, known, or suspected autoimmune disease. Patients with Type I\r\n             diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only\r\n             requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or\r\n             alopecia) not requiring systemic treatment are permitted to enroll. For any cases of\r\n             uncertainty, it is recommended to discuss with sponsor prior to signing informed\r\n             consent.\r\n\r\n          4. Significant history of cardiac disease (i.e., unstable angina, congestive heart\r\n             failure, as defined by the New York Heart Association [NYHA] as Class II, III, or IV)\r\n             within 6 months prior to Day 1 of Cycle 1, myocardial infarction within the previous\r\n             year, or current cardiac ventricular arrhythmias requiring medication., or left\r\n             ventricular ejection fraction (LVEF) is below 50%.\r\n\r\n          5. Arterial or venous thrombotic or embolic events such as cerebrovascular accident\r\n             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism\r\n             within 6 months before the start of study treatment.\r\n\r\n          6. Any hemorrhage or bleeding event CTCAE Grade 3 within 28 days prior to the start of\r\n             study treatment.\r\n\r\n          7. Has a history of (non-infectious) pneumonitis that required steroids or current\r\n             pneumonitis.\r\n\r\n          8. Patients with active tuberculosis or history of tuberculosis.\r\n\r\n          9. Any serious or uncontrolled medical disorder or active infection that, in the opinion\r\n             of the investigator, may increase the risk associated with study participation, study\r\n             drug administration, or would impair the ability of the patient to receive study drug.\r\n\r\n         10. Patients with any active infections requiring systemic therapy within 2 weeks prior to\r\n             the initiation of the study treatment.\r\n\r\n         11. Known history of positive test for human immunodeficiency virus (HIV) or known\r\n             acquired immunodeficiency syndrome (AIDS).\r\n\r\n         12. Subjects who are hepatitis C virus (HCV) antibody positive at screening, must not be\r\n             enrolled until further definite testing with HCV RNA tests can conclusively rule out\r\n             the presence of active infection (HCV RNA exceeding the lower detection limit)\r\n             requiring antiviral therapy for Hepatitis C.\r\n\r\n         13. History of organ transplantation requiring the use of immunosuppressive treatment.\r\n\r\n             Prior treatments\r\n\r\n             3. Patients who have received systemic anti-tumor treatments 21 days prior to the\r\n             initiation of the study treatment, including chemotherapy, immunotherapy, biological\r\n             therapy (tumor vaccine, cytokines, or growth factors controlling the progression of\r\n             cancers).\r\n\r\n             4. Patients who received radiotherapy within 4 weeks prior to start of study drug.\r\n             Palliative radiotherapy for symptomatic control is acceptable (if completed at least 2\r\n             weeks prior to study drug administration) and no additional radiotherapy for the same\r\n             lesion is planned.\r\n\r\n             5. Major surgical procedure, open biopsy, or significant traumatic injury within 28\r\n             days prior to initiation of study treatment, or anticipation of need for major\r\n             surgical procedure during the course of the study.\r\n\r\n             6. Has had a minor surgery (i.e. simple excision, tooth extraction)  7 days prior to\r\n             the first dose of study treatment is permitted; 7. Patients who have received\r\n             treatment with NMPA approved anti-tumor Chinese herbal medicine or Chinese prepared\r\n             medicine within 14 days prior to the initiation of the study treatment.\r\n\r\n             8. Has received locoregional therapy to liver (transchetheter chemoembolization\r\n             (TACE), transchetheter embolization (TAE), hepatic arterial infusion(HAI), radiation,\r\n             radioemboliztion or ablation) within 4 weeks of start of study treatment. Has received\r\n             Y90-selective internal radiation therapy (SIRT) within 90 days or 5 half-lives\r\n             (whichever is longer) prior to the first dosing.\r\n\r\n             9. Patients with a condition requiring systemic treatment with either corticosteroids\r\n             (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within\r\n             14 days of study drug administration. Inhaled or topical steroids, and adrenal\r\n             replacement doses  10 mg daily prednisone equivalents are permitted in the absence of\r\n             active autoimmune disease. A brief course of corticosteroids for the prophylaxis\r\n             (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g.,\r\n             delayed-type hypersensitivity reaction caused by contact allergen) is permitted.\r\n\r\n             10. Subjects with history of life-threatening toxicity related to prior immune therapy\r\n             (e.g., anti-PD-1/PD-L1 treatment) except those that are unlikely to re-occur with\r\n             standard countermeasures (e.g., Hormone replacement after adrenal crisis); 11. Only\r\n             patients in Phase II (except cohort 1, HCC): Prior treatment with an anti-PD-1,\r\n             anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137, anti-TIM-3, anti-LAG-3 antibody, or\r\n             any other antibody or drug specifically targeting T-cell co stimulation or checkpoint\r\n             pathways.\r\n\r\n             12. Administration of a live or attenuated vaccine within 28 days prior to initiation\r\n             of study treatments.\r\n\r\n             Allergies and Adverse Drug Reaction 13. History of allergy or hypersensitivity, or any\r\n             contraindications to study drug components.\r\n\r\n             Other Exclusion Criteria\r\n\r\n             14. Patients with a known history of alcoholism or drug abuse. 15. Female patients who\r\n             are pregnant or breast-feeding. 16. Patients with a history of mental illness, or who\r\n             are incapacitated or have limited capacity.\r\n\r\n             17. Other conditions that, in the investigators' opinion, would make patients\r\n             inappropriate to participate in this study.\r\n\r\n             18. Patients who are anticipating in other clinical studies or the planned first dose\r\n             of study treatment is less than 4 weeks after the last dose of treatment in previous\r\n             clinical study.\r\n      ","sponsor":"Suzhou Kintor Pharmaceutical Inc,","sponsor_type":"Industry","conditions":"Solid Tumor","interventions":[{"intervention_type":"Drug","name":"Drug: GT90001+KN046","description":"GT90001 7.0mg/Kg KN046 5mg/Kg"},{"intervention_type":"Drug","name":"Drug: GT90001+KN046","description":"GT90001 7.0mg/Kg  KN046 3mg/Kg"},{"intervention_type":"Drug","name":"Drug: GT90001/KN046","description":"GT90001 4.5mg/Kg / KN046 5mg/Kg"},{"intervention_type":"Drug","name":"Drug: GT90001+KN046","description":"GT90001 4.5mg/Kg KN046 3mg/Kg"},{"intervention_type":"Drug","name":"Drug: GT90001+KN046","description":"GT90001 3mg/Kg  KN046 3mg/Kg"}],"outcomes":[{"outcome_type":"primary","measure":"Treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs), serious adverse events (SAEs), Dose Limiting Toxicities (DLTs)","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"safety"},{"outcome_type":"primary","measure":"Phase 2 dose (RP2D) of GT90001 in combination with KN046","time_frame":"after completion of the DLT evaluation of the last subject of Phase Ib, up to 28 days","description":"RP2D"},{"outcome_type":"primary","measure":"Objective response rate","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"Efficacy"},{"outcome_type":"secondary","measure":"ORR (Phase Ib) in %, disease control rate (DCR) in %, progression-free survival (PFS)in months, and duration of response (DoR) in %","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"Efficacy"},{"outcome_type":"secondary","measure":"AUC0-t, Cmax, Tmax, t½ , CLss for GT90001 , Ctroug for KN046 (only Phase Ib)","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"Pharmacokinetic evaluations"},{"outcome_type":"secondary","measure":"occurrence of anti-GT90001 and anti-KN046 antibody","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"immunogenecity"},{"outcome_type":"secondary","measure":"TEAEs, severity of TEAEs, TRAEs, SAEs","time_frame":"until progression or death,whichever came first, assessed up to 2 years","description":"safety"}]}
{"nct_id":"NCT04964284","start_date":"2021-08-31","phase":"Phase 3","enrollment":328,"brief_title":"Efficacy and Safety Study of rhTSH for Adjuvant Radioiodine Ablation Therapy in Patients With Differentiated Thyroid Cancer","official_title":"A Randomized, Open-label, Multi-center, Controlled Phase  Study to Evaluate the Safety and Efficacy of Recombinant Human Thryoid Stimulating HormonerhTSH for Adjuvant Radioiodine Ablation Therapy in Postoperative Patients With Differentiated Thyroid Cancer","primary_completion_date":"2022-09-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2022-12-31","last_update":"2021-07-16","description":"This study was conducted in patients with differentiated thyroid cancer who had undergone total/near-total thyroidectomy. After surgery patients were randomized to one of two methods of performing thyroid remnant ablation. One group of patients who took thyroid hormone medicine and were euthyroid [i.e. their thyroid stimulating hormone (TSH) levels are normal], and received injections of rhTSH (0.9 mg daily on two consecutive days) followed by oral radioiodine. The second group of patients did not take thyroid hormone medicine so that they were hypothyroid (i.e. their TSH levels were high), and were given oral radioiodine.","other_id":"ZGTSH003","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Subjects voluntarily sign the informed consent form (ICF).\r\n\r\n          -  Age  18 years old, either male or female.\r\n\r\n          -  Patients with diagnosed differentiated papillary or follicular thyroid carcinoma,\r\n             including papillary-follicular variant, characterized as pT 1-3, N 0-1or Nx, and M0.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) score of 0-2;\r\n\r\n          -  Expected life expectancy is greater than 12 weeks;\r\n\r\n          -  Patients with a total or near-total thyroidectomy within 12 months prior to\r\n             randomized.\r\n\r\n          -  Low iodine diet for two weeks prior to randomized.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  patients with recent history of 131I whole body scan within 2 weeks prior to\r\n             randomized.\r\n\r\n          -  Pregnant or breast feeding women.\r\n\r\n          -  patients with other malignancies (exception for in situ cervix uterine cancer, baso\r\n             cellular skin cancer or breast cancer in remission)\r\n\r\n          -  Subjects who are unsuitable to the trial in combination with other serious diseases,\r\n             as identified by the investigator.\r\n\r\n          -  Subjects who have participated in another clinical trial of a new drug or medical\r\n             instrument within 1 months before screening.\r\n      ","sponsor":"Suzhou Zelgen Biopharmaceuticals Co.,Ltd","sponsor_type":"Industry","conditions":"Differentiated Thyroid Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: rhTSH","description":"rhTSH (0.9 mg) was administered intramuscularly (IM) once daily (qd) for 2 days. Twenty-four hours following the second dose of rhTSH"},{"intervention_type":"Radiation","name":"Radiation: Radioiodine (131I)","description":"Patients were given an ablative dose of 131I (30 mCi1.5 mCi)."}],"outcomes":[{"outcome_type":"primary","measure":"The rate of successful postoperative thyroid ablation","time_frame":"8 months later by a rhTSH stimulated radioiodine scan","description":"Patients were considered successfully ablated if there was no visible thyroid bed uptake on the scan"}]}
{"nct_id":"NCT04916002","start_date":"2021-08-31","phase":"Phase 2","enrollment":268,"brief_title":"CMP-001 in Combination With IV PD-1-Blocking Antibody in Subjects With Certain Types of Advanced or Metastatic Cancer","official_title":"A Multicenter, Open-label, Phase 2 Study of Intratumoral CMP-001 in Combination With an Intravenous PD-1-Blocking Antibody in Subjects With Selected Types of Advanced or Metastatic Cancer","primary_completion_date":"2022-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-31","last_update":"2021-08-12","description":"CMP-001-009 is a Phase 2 study of intratumoral CMP-001 in combination with an intravenous PD-1-blocking antibody administered to participants with certain types of advanced or metatastic cancer. The primary objective of the study is to determine the Investigator-assessed confirmed objective response with CMP-001 in combination with a programmed cell death protein (PD-1)-blocking antibody in subjects with certain types of advanced or metatastic cancer. The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with a PD-1-blocking antibody in study subjects. - To evaluate the efficacy of CMP-001 in combination with a PD-1-blocking antibody in study subjects. Participants will continue to receive treatment of CMP-001 in combination with a PD-1-blocking antibody according to the treatment schedule until a reason for treatment discontinuation is reached.","other_id":"CMP-001-009","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"3 cohorts each with 2 sub cohorts","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Subjects enrolled in the study must meet all of the following inclusion criteria to be\r\n        eligible.\r\n\r\n          1. Histopathologically-confirmed diagnosis of cancer that is metastatic or unresectable\r\n             at Screening.\r\n\r\n               1. Subjects with metastatic or locally and/or regionally advanced unresectable CSCC.\r\n\r\n                  Note 1: CSCC subjects without radiographically measurable disease are not\r\n                  excluded if there is at least 1 lesion  10 mm in at least 1 dimension documented\r\n                  by color photography. Note 2: Subjects with tumors that arise in the setting of\r\n                  chronic inflammation (Marjolin's ulcer) such as chronic wounds and/or scars are\r\n                  excluded. Cohort A1: Subjects who have not received prior systemic therapy for\r\n                  CSCC. Cohort A2: Subjects who have progressed while receiving PD-1-blocking\r\n                  antibody(ies) or within 3 months of discontinuation. PD-1-blocking antibody\r\n                  treatment may have been administered in the adjuvant and/or neoadjuvant and/or\r\n                  metastatic setting. The PD-1-blocking antibody must have been the most recent\r\n                  therapy received.\r\n\r\n               2. Subjects with metastatic or locally and/or regionally advanced unresectable MCC.\r\n\r\n                  Note: MCC subjects without radiographically measurable disease are not excluded\r\n                  if there is at least 1 lesion  10 mm in at least 1 dimension documented by color\r\n                  photography. Cohort B1: Subjects who had not received prior systemic therapy for\r\n                  MCC. Cohort B2: Subjects who have progressed while receiving PD-1-blocking\r\n                  antibody(ies) or within 3 months of discontinuation. PD-1-blocking antibody\r\n                  treatment may have been administered in the adjuvant and/or neoadjuvant and/or\r\n                  metastatic setting. The PD-1-blocking antibody must have been the most recent\r\n                  therapy received.\r\n\r\n               3. Previously treated subjects with advanced or metastatic TNBC must have disease\r\n                  that is HER2-negative, estrogen and progesterone receptor-negative, or < 5%\r\n                  expression based on American Society of Clinical Oncology/College of American\r\n                  Pathologists guidelines.\r\n\r\n                  Patients with disease recurrence or progression following neoadjuvant or adjuvant\r\n                  therapy are eligible. Patients with advanced or metastatic disease may have up to\r\n                  5 lines of systemic therapy. Cohort C1: Subjects who had not received prior\r\n                  therapy with iCPIs. Cohort C2: Subjects who had received prior treatment with\r\n                  PD-1-blocking antibody(ies).\r\n\r\n               4. Subjects enrolled in Cohorts A2, B2, and C2 must have PD on or within 3 months of\r\n                  discontinuation of prior PD-1-blocking antibody therapy, either as a single agent\r\n                  or in combination with a standard or an investigational therapy.\r\n\r\n               5. Subjects who progressed on/within 3 months of adjuvant or neoadjuvant therapy\r\n                  with iCPI will be allowed in Cohorts A2, B2, and C2.\r\n\r\n          2. Measurable disease, as defined by RECIST v1.1 and all of the following:\r\n\r\n               1. At least 1 accessible lesion amenable to repeated IT injection.\r\n\r\n               2. A previously irradiated lesion may be used as a target lesion if subsequent\r\n                  disease progression in that lesion was documented.\r\n\r\n          3. Able to provide tissue from a core or excisional/incisional biopsy (fine needle\r\n             aspirate is not sufficient). A newly obtained biopsy (within 90 days before the start\r\n             of study treatment) is preferred but an archival sample is acceptable if no\r\n             intervening therapy was received.\r\n\r\n          4. Adequate organ function based on most recent laboratory values within 3 weeks before\r\n             first dose of study treatment on Week 1 Day 1 (W1D1):\r\n\r\n               1. Bone marrow function:\r\n\r\n                    -  neutrophil count  1500/mm3\r\n\r\n                    -  platelet count  100,000/mm3\r\n\r\n                    -  hemoglobin concentration  9 g/dL\r\n\r\n               2. Liver function:\r\n\r\n                    -  total bilirubin  1.5 times the upper limit of normal (ULN) with the\r\n                       following exception: subjects with Gilbert Disease total serum bilirubin  3\r\n                       times ULN\r\n\r\n                    -  aspartate aminotransferase and alanine aminotransferase  3 times the ULN\r\n\r\n               3. Renal function: estimated (Cockcroft-Gault) or measured creatinine clearance\r\n\r\n                   30 mL/min\r\n\r\n               4. Coagulation:\r\n\r\n                    -  International normalized ratio or prothrombin time (PT)  1.5 times ULN\r\n                       unless subject is receiving anticoagulant therapy, as long as PT or partial\r\n                       thromboplastin time (PTT) is within therapeutic range of intended use of\r\n                       anticoagulants.\r\n\r\n                    -  Activated partial thromboplastin time or PTT  1.5 times ULN unless subject\r\n                       is receiving anticoagulant therapy, as long as PT or PTT is within\r\n                       therapeutic range of intended use of anticoagulants.\r\n\r\n          5. Age  18 years at time of consent.\r\n\r\n          6. Eastern Cooperative Oncology Group Performance Status of 0 to 1 at Screening.\r\n\r\n          7. Capable of understanding and complying with protocol requirements.\r\n\r\n          8. Women of childbearing potential must have negative serum pregnancy test during\r\n             Screening and be willing to use an adequate method of contraception from the time of\r\n             consent until at least 150 days after last dose of study treatment.\r\n\r\n          9. Able and willing to provide written informed consent and to follow study instructions.\r\n\r\n        Subjects unable to provide written informed consent on their own behalf will not be\r\n        eligible for the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Subjects presenting with any of the following will not qualify for entry into the study:\r\n\r\n          1. Received radiation therapy (or other nonsystemic therapy) within 2 weeks before first\r\n             dose of study treatment on W1D1. Subjects should have recovered (ie, Grade  1 or at\r\n             baseline) from radiation-related toxicities.\r\n\r\n          2. Treatment with complementary medications (eg, herbal supplements or traditional\r\n             Chinese medicines) to treat the disease under study within 2 weeks prior to start of\r\n             study treatment or at any time during the treatment phase of the study.\r\n\r\n          3. Received systemic pharmacologic doses of corticosteroids > 10 mg/day prednisone within\r\n             30 days before first dose of study treatment on W1D1.\r\n\r\n               1. Subjects who are currently receiving steroids at a prednisone-equivalent dose of\r\n\r\n                   10 mg/day do not need to discontinue steroids prior to enrollment.\r\n\r\n               2. Replacement doses, topical, ophthalmologic, and inhalational steroids are\r\n                  permitted.\r\n\r\n               3. Stress-dose corticosteroids will be required in subjects with adrenal\r\n                  insufficiency.\r\n\r\n          4. History of immune-mediated AE leading to permanent discontinuation due to prior\r\n             PD-1-blocking antibody.\r\n\r\n          5. Not fully recovered from AEs due to prior treatment (to Grade 1 or less, per CTCAE),\r\n             with the exception of persistent alopecia, hypothyroidism, or adrenal insufficiency.\r\n             Note: Subjects previously treated with a CTLA-4-blocking antibody, subjects receiving\r\n             corticosteroids with daily doses >5mg and 10mg of prednisone equivalent for >2 weeks,\r\n             and subjects with clinical symptoms and/or laboratory findings suggesting risk for\r\n             adrenal insufficiency should undergo diagnostic tests for adrenal insufficiency via\r\n             local laboratory.\r\n\r\n          6. Active pneumonitis, history of noninfectious pneumonitis that required steroids, or\r\n             history of interstitial lung disease.\r\n\r\n          7. Severe uncontrolled cardiac disease within 6 months of Screening, including but not\r\n             limited to poorly controlled hypertension, unstable angina, myocardial infarction,\r\n             congestive heart failure (New York Heart Association Class II or greater),\r\n             pericarditis within the previous 6 months, cerebrovascular accident, or implanted or\r\n             continuous use of a pacemaker or defibrillator.\r\n\r\n          8. Known history of immunodeficiency.\r\n\r\n          9. Known additional malignancy that is progressing or required active treatment within\r\n             the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell\r\n             carcinoma of the skin that has undergone potentially curative therapy, curatively\r\n             treated localized prostate cancer with prostate-specific antigen level below 4.0\r\n             ng/mL, in situ cervical cancer on biopsy or a squamous intraepithelial lesion on\r\n             Papanicolaou smear, and thyroid cancer (except anaplastic), and adjuvant hormonal\r\n             therapy for breast cancer > 3 years from curative-intent surgical resection.\r\n\r\n         10. Active autoimmune disease that required systemic treatment in past 2 years;\r\n             replacement therapy is not considered a form of systemic treatment.\r\n\r\n         11. Untreated, symptomatic, or enlarging central nervous system metastases or\r\n             carcinomatous meningitis (including leptomeningeal metastases from solid tumors).\r\n\r\n         12. Prior allogenic tissue/solid organ transplant.\r\n\r\n         13. Active infection requiring systemic therapy.\r\n\r\n         14. Known or suspected active infection with severe acute respiratory syndrome coronavirus\r\n             2 (SARS-CoV-2).\r\n\r\n         15. Known or suspected infection with human immunodeficiency virus, hepatitis B virus, or\r\n             hepatitis C virus (testing is not required unless suspected).\r\n\r\n         16. Received a live virus/attenuated vaccination within 30 days before first dose of study\r\n             treatment on W1D1.\r\n\r\n         17. Received blood products (including platelets or red blood cells) or colony stimulating\r\n             factors (including granulocyte colony stimulating factor, granulocyte/macrophage\r\n             colony stimulating factor, or recombinant erythropoietin) within 3 weeks before the\r\n             W1D1 visit.\r\n\r\n         18. History of permanent discontinuation of cemiplimab-rwlc due to infusion reactions.\r\n\r\n         19. Any concurrent uncontrolled illness, including mental illness or substance abuse,\r\n             which in the opinion of the Investigator would make the subject unable to cooperate or\r\n             participate in the study.\r\n\r\n         20. Participation in another clinical study of an investigational anticancer therapy or\r\n             device within 30 days before first dose of study treatment on W1D1. Note:\r\n             Participation in the follow-up phase (receiving no study treatment) of a prior study\r\n             is allowed.\r\n\r\n         21. Requires prohibited treatment (ie, non-protocol specified anticancer pharmacotherapy,\r\n             surgery, or conventional radiotherapy) for treatment of malignant tumor.\r\n\r\n         22. Has a life expectancy of less than 3 months and/or has rapidly progressing disease\r\n             (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating\r\n             Investigator.\r\n\r\n         23. Received previous CMP-001 treatment.\r\n\r\n         24. Pregnant or breastfeeding or expecting to conceive children within the projected\r\n             duration of the study, from the time of consent until at least 150 days after last\r\n             dose of study treatment.\r\n      ","sponsor":"Checkmate Pharmaceuticals","sponsor_type":"Industry","conditions":"Advanced Cancer|Metastatic Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: CMP-001","description":"Subjects will receive CMP-001 10mg IT weekly for 7 doses after which CMP-001 will be administered every 3 weeks (Q3W). The first dose of CMP-001 may be administered subcutaneously (SC) or IT at the discretion of Investigator. All subsequent doses will be IT. The initial 7 doses of CMP-001, delivered on a weekly dosing schedule, must be completed before starting the Q3W CMP-001 dosing schedule."},{"intervention_type":"Drug","name":"Drug: cemiplimab-rwlc","description":"Subjects will receive cemiplimab-rwlc 350 mg IV over 30 minutes at W1D1 and Q3W thereafter."}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate (ORR) with CMP-001 in combination with a programmed cell death protein 1 (PD-1)-blocking antibody (cemiplimab-rwlc) in study subjects with metastatic or advanced/unresectable CSCC, MCC, or TNBC","time_frame":"From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)","description":"CSCC is defined as cutaneous squamous cell carcinoma, MCC is defined as Merkel cell carcinoma, and TNBC is defined as triple negative breast cancer. ORR is further defined as the proportion of subjects with a confirmed objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)."},{"outcome_type":"secondary","measure":"Safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with a PD-1-blocking antibody (cemiplimab-rwlc) in the study subjects","time_frame":"From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)","description":"Safety and tolerability is defined as the presence of Adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death, and severity of AEs as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)"},{"outcome_type":"secondary","measure":"Efficacy of CMP-001 in combination with a PD-1-blocking antibody (cemiplimab-rwlc) in the study subjects","time_frame":"From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)","description":"Efficacy is measured by: Duration of response (DOR), defined as the time from date of first documented response (CR or PR) to date of documented progressive disease (PD), based on RECIST v1.1 Immune ORR, DOR, and progression-free survival (iORR, iDOR, and iPFS) based on immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) treatment response in noninjected target lesions based on RECIST v1.1. Response in injected and noninjected target lesions per RECIST v1.1. Progression-free survival (PFS), defined as the time from date of first dose of study treatment to date of documented PD based on RECIST v1.1 or death, whichever occurs first. Overall survival (OS), defined as the time from date of first dose of study treatment to date of death"}]}
{"nct_id":"NCT04892446","start_date":"2021-08-31","phase":"Phase 2","enrollment":153,"brief_title":"Study of Magrolimab Combinations in Participants With Relapsed/Refractory Multiple Myeloma","official_title":"A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma","primary_completion_date":"2023-09-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-09-30","last_update":"2021-08-25","description":"The primary objective of this study for the Safety Run-in Cohorts is to evaluate the safety and tolerability of magrolimab in combination with other anticancer therapies and to determine the recommended Phase 2 dose (RP2D) of magrolimab in participants with relapsed/refractory multiple myeloma (MM) for the following combinations: magrolimab + daratumumab, magrolimab + pomalidomide + dexamethasone, and magrolimab + bortezomib + dexamethasone. The primary objective of this study for the Dose Expansion Cohorts is to evaluate the efficacy of magrolimab in combination with other anticancer therapies in participants with relapsed/refractory multiple myeloma as determined by objective response rate (ORR).","other_id":"GS-US-558-5915","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n        All Individuals:\r\n\r\n          -  Individual has been previously diagnosed with MM based on the IMWG 2016 criteria and\r\n             currently requires treatment.\r\n\r\n          -  Individuals must have measurable disease as defined by 1 or more of the following:\r\n\r\n               -  Serum monoclonal protein (M-protein)  0.5 grams per deciliter (g/dL) (greater\r\n                  than or equal to [] 5 grams per liter [g/L]).\r\n\r\n               -  Urine M-protein  200 mg/24 hours (h).\r\n\r\n               -  Serum free light chain (SFLC) assay: involved SFLC level  10 mg/dL (100 mg/L)\r\n                  with abnormal SFLC ratio.\r\n\r\n          -  Individuals must have received at least 3 previous lines of therapy for MM including\r\n             an IMiD such as lenalidomide and a PI such as bortezomib.\r\n\r\n          -  Individual has provided informed consent.\r\n\r\n          -  Individual is willing and able to comply with clinic visits and procedure outlined in\r\n             the study protocol.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status  2.\r\n\r\n          -  Life expectancy  3 months.\r\n\r\n          -  Absolute neutrophil count (ANC)  1000 cells/dL (1.0 x 10^9/L); granulocyte\r\n             colony-stimulating factor (G-CSF) is not permitted within 1 week of screening to meet\r\n             eligibility criteria.\r\n\r\n          -  Platelet count  75,000 cells/dL (75 x 10^9/L); platelet transfusion is not permitted\r\n             within 1 week of screening to meet eligibility criteria.\r\n\r\n          -  Hemoglobin  9.0 g/dL; no more than 4 units of packed Red blood cells (RBCs) are\r\n             allowed in the 30 days prior to screening.\r\n\r\n          -  For Individuals with prior cardiac history such as ischemic heart disease, left\r\n             ventricular ejection fraction  45%, symptomatic congestive heart failure, New York\r\n             Heart Association (NYHA) Class III or IV heart failure, or other conditions that may\r\n             be sensitive to demand ischemia, the hemoglobin must be  9.5 g/dL prior to initial\r\n             dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility\r\n             criterion.\r\n\r\n          -  Adequate liver function as demonstrated by the following:\r\n\r\n               -  Aspartate aminotransferase (AST)  3.0 x upper limit of normal (ULN).\r\n\r\n               -  Alanine aminotransferase (ALT)  3.0 x ULN.\r\n\r\n               -  Total bilirubin  1.5 x ULN (or  3.0 x ULN and primarily unconjugated if\r\n                  individual has a documented history of Gilbert's syndrome or genetic equivalent).\r\n\r\n          -  Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin\r\n             time  1.2; Individuals receiving anticoagulation treatment may be allowed to\r\n             participate if INR is within the therapeutic range prior to alternate assignment.\r\n\r\n          -  Individuals must have adequate renal function as demonstrated by a creatinine\r\n             clearance  30 mL/min calculated by the Cockcroft-Gault formula or measured by 24\r\n             hours urine collection.\r\n\r\n          -  Corrected serum calcium  2.9 millimoles per liter (mmol/L) (11.5 mg/dL); measures to\r\n             reduce calcium to acceptable levels, such as a short course of steroids,\r\n             bisphosphonates, hydration, or calcitonin are acceptable.\r\n\r\n          -  Pretreatment blood cross-match completed.\r\n\r\n          -  Male and female individuals of childbearing potential who engage in heterosexual\r\n             intercourse must agree to use protocol-specified method(s) of contraception.\r\n\r\n          -  Individuals must be willing to consent to mandatory pretreatment and on-treatment bone\r\n             marrow biopsies (trephines).\r\n\r\n          -  Magrolimab in Combination with Daratumumab: In addition to fulfilling the inclusion\r\n             criteria for all individuals, individuals who are assigned to receive magrolimab in\r\n             combination with daratumumab should fulfill the following:\r\n\r\n               -  Individuals must have CD38-positive myeloma and have not had prior anti-CD38\r\n                  antibody therapy for at least 6 months prior to enrollment.\r\n\r\n               -  No prior history of discontinuation of daratumumab due to toxicity.\r\n\r\n          -  Magrolimab in Combination with Pomalidomide and Dexamethasone: In addition to\r\n             fulfilling the inclusion criteria for all Individuals, Individuals who are assigned to\r\n             receive magrolimab in combination with pomalidomide and dexamethasone should fulfill\r\n             the following:\r\n\r\n               -  Prior treatment with pomalidomide is allowed if the Individual achieved at least\r\n                  a PR to the most recent pomalidomide therapy and will have had at least a 6-month\r\n                  treatment-free interval from the last dose of pomalidomide until first study\r\n                  treatment.\r\n\r\n               -  No prior history of discontinuation of pomalidomide due to toxicity.\r\n\r\n               -  No contraindication to dexamethasone.\r\n\r\n          -  Magrolimab in Combination with Bortezomib and Dexamethasone: In addition to fulfilling\r\n             the inclusion criteria for all individuals, individuals who are assigned to receive\r\n             magrolimab in combination with bortezomib and dexamethasone should fulfill the\r\n             following:\r\n\r\n               -  Prior treatment with a PI, including bortezomib, is allowed if the Individual\r\n                  achieved at least a PR to the most recent prior PI therapy, and will have had at\r\n                  least a 6-month PI treatment-free interval from the last dose until first study\r\n                  treatment.\r\n\r\n               -  No prior history of discontinuation of bortezomib due to toxicity.\r\n\r\n               -  No contraindication to dexamethasone.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Individuals with known amyloidosis including myeloma complicated by amyloidosis.\r\n\r\n          -  Multiple myeloma of immunoglobulin M subtype.\r\n\r\n          -  Individuals with Waldenstrom's macroglobulinemia.\r\n\r\n          -  Individuals with myelodysplastic syndrome (MDS).\r\n\r\n          -  Plasma cell leukemia (defined as either 20% of peripheral blood white blood cell (WBC)\r\n             count comprised of plasma/CD138-positive cells) or circulating plasma cells  2 x\r\n             10^9/L.\r\n\r\n          -  Individuals with solitary bone or extramedullary plasmacytoma as the only evidence of\r\n             plasma cell dyscrasia.\r\n\r\n          -  Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS)\r\n             syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,\r\n             M-protein, and skin changes).\r\n\r\n          -  Glucocorticoid therapy (prednisone > 40 mg/day or equivalent) within 14 days prior to\r\n             enrollment; corticosteroid therapy for hypercalcemia is allowed.\r\n\r\n          -  Chemotherapy with approved or investigational anticancer therapeutics within 28 days\r\n             prior to enrollment.\r\n\r\n          -  Focal radiation therapy within 7 days prior to enrollment; radiation therapy to an\r\n             extended field involving a significant volume of bone marrow within 21 days prior to\r\n             enrollment (ie, prior radiation must have been to less than 30% of the bone marrow).\r\n\r\n          -  Immunotherapy within 28 days prior to enrollment.\r\n\r\n          -  Major surgery (excluding procedures to stabilize the vertebrae) within 28 days prior\r\n             to enrollment.\r\n\r\n          -  Positive serum pregnancy test.\r\n\r\n          -  Breastfeeding female.\r\n\r\n          -  Known hypersensitivity to any of the study drugs, the metabolites, or formulation\r\n             excipient.\r\n\r\n          -  Prior treatment with CD47 or signal regulatory protein alpha (SIRP)-targeting agents.\r\n\r\n          -  Current participation in another interventional clinical trial.\r\n\r\n          -  Autologous stem cell transplant < 100 days prior to enrollment.\r\n\r\n          -  Considered eligible to receive autologous or allogeneic stem cell transplant (SCT) at\r\n             the time of enrollment.\r\n\r\n          -  Allogeneic SCT for the treatment of MM within 6 months of enrollment or active\r\n             graft-versus-host disease requiring immunosuppression.\r\n\r\n          -  Significant neuropathy (Grade 3 to 4, or Grade 2 with pain) within 14 days prior to\r\n             enrollment.\r\n\r\n          -  Known inherited or acquired bleeding disorders.\r\n\r\n          -  Known cirrhosis.\r\n\r\n          -  Clinical suspicion or documentation of central nervous system (CNS) disease.\r\n\r\n          -  Significant disease or medical conditions, as assessed by the investigator and\r\n             sponsor, that would substantially increase the risk-benefit ratio of participating in\r\n             the study. This includes, but is not limited to, acute myocardial infarction within\r\n             the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active\r\n             infections, congestive heart failure, or New York Heart Association (NYHA) Class III\r\n             or IV heart failure.\r\n\r\n          -  Acute active infection requiring systemic antibiotics, antiviral (except antiviral\r\n             therapy directed against reactivation) or antifungal agents within 14 days prior to\r\n             enrollment.\r\n\r\n          -  Second malignancy, except treated basal cell or localized squamous skin carcinomas,\r\n             localized prostate cancer, or other malignancies for which patients are not on active\r\n             anticancer therapies and have had no evidence of active malignancy for at least 1\r\n             year. Other exceptions may be considered with sponsor approval. Previous hormonal\r\n             therapy with luteinizing hormone-releasing hormone agonists for prostate cancer and\r\n             treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand\r\n             (RANKL) inhibitors are not criteria for exclusion.\r\n\r\n          -  Known active or chronic hepatitis B or C infection or human immunodeficiency virus\r\n             (HIV) infection in medical history.\r\n\r\n          -  Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV\r\n             infection following testing at screening:\r\n\r\n               -  Individuals who test positive for hepatitis B surface antigen (HBsAg). Patients\r\n                  who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA\r\n                  by quantitative polymerase chain reaction (PCR) for confirmation of active\r\n                  disease.\r\n\r\n               -  Individuals who test positive for HCV antibody. Patients who test positive for\r\n                  HCV antibody will require HCV ribonucleic acid (RNA) by quantitative PCR for\r\n                  confirmation of active disease.\r\n\r\n               -  Individuals who test positive for HIV.\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"Gilead Sciences","sponsor_type":"Industry","conditions":"Multiple Myeloma","interventions":[{"intervention_type":"Biological","name":"Biological: Magrolimab","description":"Administered IV"},{"intervention_type":"Drug","name":"Drug: Daratumumab","description":"Administered either SC or IV"},{"intervention_type":"Drug","name":"Drug: Pomalidomide","description":"Administered orally"},{"intervention_type":"Drug","name":"Drug: Dexamethasone","description":"Administered orally"},{"intervention_type":"Drug","name":"Drug: Bortezomib","description":"Administered either SC or IV"}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Safety Run-in Cohorts)","time_frame":"First dose date up to the end of the first dosing cycle (Cycle 1=35 days)","description":"A DLT is defined as any Grade 3 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (with some pre-specified exceptions), that has worsened in severity from pretreatment baseline during the DLT assessment period and, in the opinion of the investigator, the adverse event (AE) is at least possibly related to magrolimab."},{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts)","time_frame":"From date of first dose of any study drug up to the date of last dose of any study drug plus 30 days (Up to 2.5 years)","description":"A treatment-emergent AE will be defined as any AE that begins on or after the date of first dose of any study drug up to the date of last dose of any study drug plus 30 days."},{"outcome_type":"primary","measure":"Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts)","time_frame":"From baseline to the date of last dose of any study drug plus 30 days (Up to 2.5 years)","description":"Treatment-emergent laboratory abnormalities will be defined as values that increase at least 1 toxicity grade from baseline to the date of last dose of any study drug plus 30 days. If baseline data are missing, then any graded abnormality (ie, at least Grade 1) will be considered a treatment-emergent abnormality."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) (Dose Expansion Cohorts)","time_frame":"Up to 2.5 years","description":"Objective response rate is defined as the percentage of participants who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Myeloma Working Group (IMWG) 2016 criteria."},{"outcome_type":"secondary","measure":"Percentage of Participants Experiencing TEAE's According to the NCI CTCAE Version 5.0 (Dose Expansion Cohorts)","time_frame":"From date of first dose of any study drug up to the date of last dose of any study drug plus 30 days. (Up to 2.5 years)","description":"A treatment-emergent AE will be defined as any AE that begins on or after the date of first dose of any study drug up to the date of last dose of any study drug plus 30 days."},{"outcome_type":"secondary","measure":"Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Dose Expansion Cohorts)","time_frame":"From baseline to the date of last dose of any study drug plus 30 days (Up to 2.5 years)","description":"Treatment-emergent laboratory abnormalities will be defined as values that increase at least 1 toxicity grade from baseline to the date of last dose of any study drug plus 30 days. If baseline data are missing, then any graded abnormality (ie, at least Grade 1) will be considered a treatment-emergent abnormality."},{"outcome_type":"secondary","measure":"Duration of Response (Dose Expansion Cohorts)","time_frame":"Up to 2.5 years","description":"Duration of response is measured from the earliest date of sCR, CR, VGPR, or PR, whichever is first recorded, until the earliest date of documented progression disease (PD), documented relapse, or death from any cause, whichever occurs first. Those who are not observed to have documented relapse, documented PD, or death will be censored at the date of their last response assessment per International Myeloma Working Group (IMWG) 2016 criteria."},{"outcome_type":"secondary","measure":"Progression-free Survival (Dose Expansion Cohorts)","time_frame":"Up to 2.5 years","description":"Progression-free survival is defined as the duration from the date of the first dose of study treatment to the earliest date of documented relapse, documented PD, or death from any cause, whichever occurs first. Those who are not observed to have documented relapse, documented PD, or death from any cause during the study will be censored at the date of their last response assessment during the study per IMWG 2016 criteria."},{"outcome_type":"secondary","measure":"Overall Survival (Dose Expansion Cohorts)","time_frame":"Up to 2.5 years","description":"Overall survival is measured from the date of the first dose of study treatment to the date of death from any cause. Those who are not observed to die during the study will be censored at last date they are known to be alive."},{"outcome_type":"secondary","measure":"Serum Concentrations of Magrolimab (Dose Expansion Cohorts)","time_frame":"Up to end of treatment (approximately 2.5 years)"},{"outcome_type":"secondary","measure":"Antidrug Antibody (ADA) Against Magrolimab (Dose Expansion Cohorts)","time_frame":"Up to end of treatment (approximately 2.5 years)"}]}
{"nct_id":"NCT04826107","start_date":"2021-08-31","phase":"Phase 2","enrollment":196,"brief_title":"Study of DP303c Injection in Patients With Advanced or Metastatic Gastric Cancer","official_title":"An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Gastric Cancer With HER2 Expression","primary_completion_date":"2024-08-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-12-31","last_update":"2021-04-01","description":"This study is an open-label, multicenter, phase II study to evaluate the efficacy and safety of DP303c injection in patients with HER2-positive advanced or metastatic gastric cancer.","other_id":"SYSA1501-CSP-003","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Volunteer to participate in this study and sign the informed consent form.\r\n\r\n          2. Age 18 and 75 years, regardless of gender.\r\n\r\n          3. Unresectable locally advanced, recurrent or metastatic gastric cancer (including\r\n             gastric-esophageal junction adenocarcinoma) confirmed by histopathology and/or\r\n             cytology; patients have received at least the first-line platinum or taxane based\r\n             treatment (Patients who have progressed or recurred during neoadjuvant/adjuvant\r\n             therapy or within 6 months after completion of treatment can participate. In this\r\n             case, neoadjuvant/adjuvant therapy can be counted as one previous (1st-line) therapy);\r\n             for each cohort in part 2, HER2-positive patients must also include trastuzumab or\r\n             trastuzumab analog in the previous 1st-line therapy.\r\n\r\n             Part 1 Progression on or after  1st-line treatment, HER2 positive. Part 2 Cohort A:\r\n             Progression on or after 1st-line treatment, HER2 positive; Cohort B: Progression on or\r\n             after  2nd-line of treatment, HER2 positive; Cohort C: Progression on or after \r\n             1st-line treatment, low expression of HER2; Cohort D: Progression on or after \r\n             1st-line treatment, HER2 low expression or HER2 positive.\r\n\r\n             HER2 positive expression is defined as IHC 3+ or IHC 2+ with ISH test positive; HER2\r\n             low expression is defined as IHC 1+ or IHC 2+ with ISH test negative.\r\n\r\n          4. Eastern Cooperative Oncology Group (ECOG) score of 0-1, and life expectancy  3\r\n             months.\r\n\r\n          5. The function of major organs must meet the following criteria within 7 days before\r\n             enrollment (Have not received blood transfusion, EPO, G-CSF or other medical\r\n             supportive treatment within 14 days before the first dose of study drug):\r\n\r\n             Absolute neutrophil count (ANC) 1.5109 /L, Platelet 100109 /L; Hemoglobin 90 g/L\r\n             or 5.6 mmol/L; International normalized ratio (INR) or prothrombin time (PT)\r\n             1.5ULN; Activated Partial Thromboplastin Time (APTT) 1.5ULN; Creatinine clearance\r\n             rate 30 mL/min (Calculated by Cockcroft-Gualt formula); Total bilirubin 1.5ULN, or\r\n             3ULN for patients with Gilbert's syndrome or liver metastasis; Aspartate\r\n             aminotransferase (AST) and Alanine aminotransferase (ALT) 2.5ULN, or 5ULN for\r\n             patient.\r\n\r\n          6. At least one measurable lesion at baseline per RECIST v1.1.\r\n\r\n          7. Women of childbearing age must have a negative pregnancy test prior to study entry.\r\n\r\n          8. Female and male patient of childbearing age must agree to take adequate contraceptive\r\n             measures during the entire study period and through at least 6 months after the last\r\n             dose of study drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Pregnant or breastfeeding women.\r\n\r\n          2. Has not recovered from adverse reactions caused by previous anti-tumor treatments to \r\n             grade 1 or baseline (refer to NCI CTCAE 5.0), except for alopecia, pigmentation and\r\n             other toxicity judged no safety risk by the investigator.\r\n\r\n          3. Patients who have previously received trastuzumab or trastuzumab analogues and have\r\n             related toxicity, resulting in permanent discontinuation.\r\n\r\n          4. Patients with history of allergy to any components (trastuzumab analogues, MMAE,\r\n             sodium citrate dihydrate, citric acid monohydrate, polysorbate 20, sucrose, etc.) of\r\n             DP303c.\r\n\r\n          5. Patients with brain or pia mater metastasis; except for patients with central nervous\r\n             system (CNS) metastases in the following conditions: untreated but asymptomatic, or\r\n             progression-free status in imaging evidence for at least 4 weeks after treatment and\r\n             not requiring hormone therapy for at least 4 weeks.\r\n\r\n          6. Patients with pleural effusions or ascites that are difficult to control (the\r\n             frequency of percutaneous drainage is more than once a week, or continuous drainage\r\n             daily volume is 500 mL).\r\n\r\n          7. The patient had acute and chronic gastrointestinal bleeding with hematemesis or melena\r\n             within 4 weeks before the first administration of study drug (except for patients with\r\n             only the fecal occult blood test positive, but without visible bleeding such as melena\r\n             or hematemesis).\r\n\r\n          8. Patients with gastrointestinal obstruction.\r\n\r\n          9. Patients with dyspnea at rest induced by complications of advanced malignant tumors or\r\n             need for continuous oxygen therapy.\r\n\r\n         10. History of any other malignant tumors within five years (except for skin basal cell\r\n             carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate\r\n             cancer, cervical cancer in situ and other malignant tumors that have been radically\r\n             removed and have not recurred).\r\n\r\n         11. History of (non-infectious) interstitial pneumonia/pulmonary disease that requires\r\n             steroid treatment, or current interstitial pneumonia/pulmonary disease, or suspected\r\n             interstitial pneumonia/pulmonary disease that cannot be excluded by imaging\r\n             examination; except for patients with radiation pneumonitis without clinical symptoms\r\n             after 3 months of radiotherapy.\r\n\r\n         12. Patients who currently have corneal diseases that require medication or surgical\r\n             intervention, or have a history of serious corneal diseases, or are unwilling to stop\r\n             wearing contact lenses during the study.\r\n\r\n         13. History of congestive heart failure, unstable angina pectoris, arrhythmia.\r\n\r\n             Patients with the following cardiac function defects at the time of enrollment:\r\n\r\n               -  New York Heart Association (NYHA) heart function classification is level III or\r\n                  IV;\r\n\r\n               -  Uncontrolled angina, congestive heart failure or myocardial infarction within 6\r\n                  months before enrollment;\r\n\r\n               -  Left ventricular ejection fraction (LVEF) <50% or lower limit of normal in\r\n                  echocardiogram (ECHO) or multi-gate detection scan (MUGA);\r\n\r\n               -  Average adjusted QT interval prolongation (male>450 ms, female>470 ms), QT\r\n                  interval corrected by Fridericia's formula (QTcF).\r\n\r\n         14. The cumulative amount of previous exposure to anthracyclines has reached the following\r\n             doses: doxorubicin or liposomal doxorubicin>500 mg/m2; epirubicin>900 mg/m2;\r\n             mitoxantrone>120 mg/m2.\r\n\r\n         15. Peripheral neuropathy  grade 2 before entry (refer to NCI CTCAE 5.0).\r\n\r\n         16. Uncontrollable electrolyte imbalances include hypokalemia, hypocalcemia or\r\n             hypomagnesemia (refer to NCI CTCAE 5.0, 2 grade).\r\n\r\n         17. Patients with active hepatitis B or C (HBsAg positive, with HBV DNA positive, and the\r\n             ALT continues to be higher than the upper limit of normal, without other causes of ALT\r\n             elevation; HCVAb positive with HCV RNA higher than the upper limit of normal).\r\n\r\n         18. Test positive for HIV or syphilis.\r\n\r\n         19. Patients have used strong CYP3A4 inhibitors (drugs that increase the AUC of specific\r\n             CYP substrates  5 times, or CYP3A4 strong inducers with a washout period less than 5\r\n             half-lives before the first dose of study drug.\r\n\r\n         20. Patients underwent major surgery within 4 weeks and did not fully recover before the\r\n             first dose of study drug.\r\n\r\n         21. Chemotherapy, radiotherapy, immunotherapy and other anti-tumor treatments within 4\r\n             weeks before the first dose of study drug, within 2 weeks for Chinese medicine\r\n             treatment with anti-tumor indications or local palliative radiotherapy for bone\r\n             metastasis and pain relief; or within 5 half-lives for oral fluorouracil and small\r\n             molecule targeted drugs.\r\n\r\n         22. Patients have received other clinical trial drugs within 4 weeks before the first dose\r\n             of study drug.\r\n\r\n         23. Have previously received antibody drug conjugate targeting HER2.\r\n\r\n         24. Other serious or uncontrollable diseases or conditions that may affect the evaluation\r\n             of the primary endpoint or the investigator believes that participation in this study\r\n             may bring risks to the patient.\r\n      ","sponsor":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd.","sponsor_type":"Industry","conditions":"Gastric Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: DP303c treatment","description":"DP303c injection, every 3 weeks."},{"intervention_type":"Drug","name":"Drug: DP303c treatmentsecond-line of HER2-positive","description":"DP303c injection, every 3 weeks."},{"intervention_type":"Drug","name":"Drug: DP303c treatment third-line of HER2-positive","description":"DP303c injection, every 3 weeks."},{"intervention_type":"Drug","name":"Drug: DP303c treatmentsecond-line of HER2 low expressing","description":"DP303c injection, every 3 weeks."},{"intervention_type":"Drug","name":"Drug: DP303c + PD-1/PD-L1 treatment","description":"DP303c injection + PD-1/PD-L1 injection, dose and frequency to be determined."}],"outcomes":[{"outcome_type":"primary","measure":"ORR(Objective Response Rate)","time_frame":"Up to 2.5 years","description":"The percentage of patients with a complete response (CR) or partial response (PR)."},{"outcome_type":"secondary","measure":"PFS(Progression Free Survival)","time_frame":"Up to 2.5 years","description":"The time from the first dose of study treatment to the date of documented disease progression, clinical progression, or death from any cause."},{"outcome_type":"secondary","measure":"OS(Overall Survival)","time_frame":"Up to 2.5 years","description":"The time from the first dose of study treatment until the date of death from any cause."},{"outcome_type":"secondary","measure":"DCR(Disease Control Rate)","time_frame":"Up to 2.5 years","description":"Number of subjects who achieved a best response of CR, PR, or SD during treatment."},{"outcome_type":"secondary","measure":"DOR(Duration of Response)","time_frame":"Up to 2.5 years","description":"The time from the first objective response (CR or PR) to documented PD, clinical progression, or death from any cause."},{"outcome_type":"secondary","measure":"AEs and SAEs","time_frame":"Up to 2.5 years","description":"Incidence of adverse events and serious adverse events."}]}
{"nct_id":"NCT04690699","start_date":"2021-08-31","phase":"Phase 1/Phase 2","enrollment":155,"brief_title":"LUMINOS-103: A Basket Trial Evaluating the Safety and Efficacy of PVSRIPO and PVSRIPO in Combination With Anti-PD-1/L1 Checkpoint Inhibitors in Patients With Advanced Solid Tumors","official_title":"LUMINOS-103: A Basket Trial Evaluating the Safety and Efficacy of PVSRIPO and PVSRIPO in Combination With Anti-PD-1/L1 Checkpoint Inhibitors in Patients With Advanced Solid Tumors","primary_completion_date":"2025-05-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-05-31","last_update":"2021-08-20","description":"This is a Phase 1/2, open-label, multi-center, single arm basket study evaluating the administration of PVSRIPO  anti programmed cell death protein 1 (PD 1)/programmed death-ligand 1 (PD L1) monoclonal antibody (mAb) (which will be referred to throughout this protocol as \"anti-PD-1/L1 therapy\") therapy in adult patients with solid tumor cancers. Bladder Cancer and Head and Neck Squamous Cell Carcinoma have been selected as the first tumor specific cancers of interest for enrollment.","other_id":"LUMINOS-103","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Master Protocol Inclusion Criteria:\r\n\r\n          1. Capable of giving signed informed consent which includes compliance with the\r\n             requirements and restrictions listed in the informed consent form (ICF) and in this\r\n             protocol.\r\n\r\n          2. Age  18 years of age at the time of signing the informed consent.\r\n\r\n          3. Prior CDC-recommended vaccination series against PV and has received a boost\r\n             immunization with trivalent Poliovirus Vaccine Inactivated (IPOL) (Sanofi-Pasteur SA)\r\n             at least 1 week, but less than 6 weeks, prior to Cycle 1 Day 1.\r\n\r\n             * Note: Patients who are unsure of their vaccination status must provide evidence of\r\n             anti-PV immunity prior to enrollment, as applicable.\r\n\r\n          4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.\r\n\r\n          5. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh\r\n             biopsy) with an associated pathology report documenting the histology of the tumor\r\n             type of interest must be confirmed to be available to send to the Sponsor.\r\n\r\n             * Note: additional details can be found in the tumor specific appendix.\r\n\r\n          6. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.\r\n\r\n          7. Adequate bone marrow and liver function as assessed by the following:\r\n\r\n               -  Hemoglobin 9.0 g/dl (patients may be transfused)\r\n\r\n               -  Lymphocyte count  0.5 x 109/L (500/L)\r\n\r\n               -  Absolute neutrophil count (ANC) 1.5 x 109/L (1500/L)\r\n\r\n               -  Platelet count 100 x 109/L (100,000/L) without transfusion\r\n\r\n               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)  2.5 x upper\r\n                  limit of normal (ULN)\r\n\r\n                    -  Subjects with documented liver metastases: AST and ALT 5 x ULN\r\n\r\n               -  Serum total bilirubin 1.5 x ULN OR direct bilirubin <ULN for patients with total\r\n                  bilirubin > 1.5 x ULN\r\n\r\n               -  For patients not receiving therapeutic anticoagulation: international normalized\r\n                  ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT) (or\r\n                  activated partial thromboplastin time [aPTT])  1.5 x ULN\r\n\r\n          8. Resolution of nonhematologic toxicities from prior therapy or surgical procedures to\r\n\r\n              Grade 1 or baseline (except alopecia).\r\n\r\n          9. Contraceptive use by men or women of childbearing potential should be consistent with\r\n             local regulations regarding the methods of contraception for those participating in\r\n             clinical studies.\r\n\r\n        Master Protocol Exclusion Criteria:\r\n\r\n          1. Any radiotherapy, chemotherapy, immunotherapy, biological, investigational, or\r\n             hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast\r\n             cancer or prostate cancer defined as M0 disease or prostate-specific antigen\r\n             persistence/recurrence without metastatic disease) within 21 days of Cycle 1 Day 1.\r\n\r\n          2. Patients requiring anticoagulation with warfarin are excluded. Additional eligibility\r\n             criteria for anticoagulation requirements for each solid tumor cancer of interest will\r\n             be provided in the tumor specific appendix.\r\n\r\n          3. Presence of central nervous system (CNS) metastases requiring immediate treatment with\r\n             radiation therapy or steroids (ie, patient must be off steroids administered for brain\r\n             metastases for  14 days prior to Cycle Day 1). Leptomeningeal disease is excluded\r\n             regardless of clinical stability or treatment status.\r\n\r\n          4. Clinically significant (ie, active) cardiovascular disease at the time of signing the\r\n             informed consent; for example, cerebrovascular accidents ( 6 months before the first\r\n             dose of PVSRIPO), myocardial infarction ( 6 months before the first dose of PVSRIPO),\r\n             unstable angina, serious cardiac arrythmia requiring medication, or uncontrolled\r\n             symptomatic congestive heart failure [Class II or higher as defined by the New York\r\n             Heart Association [NYHA] functional classification system; see Appendix 4]).\r\n\r\n          5. QTcF interval > 450 msec (males) or > 470 msec (females) at Screening (confirmed in\r\n             triplicate). For patients with ventricular pacemakers or bundle branch block, QTcF\r\n             >500 msec.\r\n\r\n          6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days\r\n             prior to Cycle Day 1, or anticipation of the need for major surgical procedure during\r\n             the course of the study.\r\n\r\n          7. Active or history of autoimmune disease or immune deficiency within previous 2 years,\r\n             with the following exceptions:\r\n\r\n               -  History of autoimmune-related hypothyroidism that is managed by thyroid\r\n                  replacement hormone\r\n\r\n               -  Type 1 diabetes mellitus that is well-controlled (as determined by the\r\n                  Investigator) by an established insulin regimen\r\n\r\n               -  Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations\r\n                  only (eg, patients with psoriatic arthritis are excluded), provided all of the\r\n                  following conditions are met:\r\n\r\n                    -  Rash must cover < 10% of body surface area\r\n\r\n                    -  Disease is well-controlled (as determined by the Investigator) at baseline\r\n                       and requires only low-potency topical corticosteroids\r\n\r\n                    -  No occurrence of acute exacerbations of the underlying condition requiring\r\n                       psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic\r\n                       agents, oral calcineurin inhibitors, or high potency or oral corticosteroids\r\n                       within 12 months of Cycle 1 Day 1\r\n\r\n          8. History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis\r\n             obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis\r\n             on screening chest computed tomography (CT) scan.\r\n\r\n               -  History of radiation pneumonitis in the radiation field (fibrosis) is allowed.\r\n\r\n          9. Uncontrolled pleural effusion, pericardial effusion, or ascites; patients with\r\n             indwelling catheters (eg, PleurX) are allowed.\r\n\r\n         10. Known serious active infection (eg, human immunodeficiency virus [HIV], hepatitis B or\r\n             C, tuberculosis, etc.).\r\n\r\n               -  Participants with a negative hepatitis B surface antigen (HBsAg) test and a\r\n                  positive total hepatitis B core antibody (HBcAb) test are allowed.\r\n\r\n               -  History of positive hepatitis C virus (HCV) antibody test, but negative HCV RNA\r\n                  test is allowed.\r\n\r\n               -  Participants with a historical positive HIV test are not allowed.\r\n\r\n         11. Treatment with systemic immunosuppressive medication within 28 days of Cycle 1 Day 1,\r\n             with the following exceptions:\r\n\r\n               -  Patients who received acute, low-dose systemic immunosuppressant medication or a\r\n                  one-time pulse dose of systemic immunosuppressant medication (eg, 48 hours of\r\n                  corticosteroids for a contrast allergy) are eligible.\r\n\r\n               -  Patients receiving mineralocorticoids (eg, fludrocortisone), or systemic\r\n                  prednisone equivalent corticosteroid doses of < 10 mg per day are eligible for\r\n                  the study.\r\n\r\n         12. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.\r\n\r\n         13. Receipt of any live, attenuated vaccines within 28 days of Cycle 1 Day 1. Vaccination\r\n             to prevent symptomatic SARS-CoV-2 infection is allowed as long as the vaccine is NOT a\r\n             live attenuated vaccine (e.g. adenovirus-based constructs); however, the vaccine\r\n             should be administered  1 week before or after a PVSRIPO injection.\r\n\r\n         14. Known hypersensitivity to any of the drugs used in this study.\r\n\r\n         15. Pregnant or lactating women.\r\n\r\n         16. History of human serum albumin allergy.\r\n\r\n         17. History of neurological complications due to PV infection.\r\n\r\n         18. History of agammaglobulinemia.\r\n\r\n         19. Legal incapacity or limited legal capacity.\r\n\r\n         20. Other uncontrolled serious chronic disease or psychiatric condition that in the\r\n             Investigator's opinion could affect the patient's safety, compliance, or follow-up in\r\n             the protocol.\r\n\r\n        Bladder Cancer Specific Inclusion Criteria:\r\n\r\n        Both Cohorts:\r\n\r\n          1. Histologically or cytologically confirmed urothelial carcinoma arising from the lower\r\n             urinary tract and amenable to intratumoral injection. Both urothelial carcinoma and\r\n             mixed urothelial/non-urothelial cell histologies are allowed. Patients with pure\r\n             non-urothelial histologies are excluded.\r\n\r\n          2. Measured or calculated (per institutional standard) creatinine clearance  45 ml/min\r\n             (GFR can also be used in place of creatinine clearance).\r\n\r\n          3. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh\r\n             biopsy if collection date of archival specimen > 6 months prior to Cycle 1 Day 1) with\r\n             an associated pathology report documenting the histology of the tumor type of interest\r\n             must be confirmed to be available to send to the Sponsor.\r\n\r\n        Cohort A:\r\n\r\n          1. Clinical stage T2-T4a, N0-1, M0 by computed tomography (CT) abdomen/pelvis urogram or\r\n             magnetic resonance imaging (MRI) abdomen/pelvis urogram.\r\n\r\n          2. Have refused or are ineligible for cisplatin-based therapy, defined as meeting one of\r\n             the following criteria. Note: the master protocol excludes patients with Eastern\r\n             Cooperative Oncology Group (ECOG)  2 or congestive heart failure New York Heart\r\n             Association (NYHA) class  II.\r\n\r\n               1. Glomerular filtration rate (GFR) < 60 mL/min calculated per institutional\r\n                  standard\r\n\r\n               2. Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 Grade  2 hearing\r\n                  loss\r\n\r\n               3. CTCAE v 5.0 Grade  2 peripheral neuropathy NOTE: the hearing loss and peripheral\r\n                  neuropathy criteria are exceptions to the criterion in the master protocol\r\n                  stating all nonhematologic toxicities from prior therapy or surgical procedures\r\n                  be  Grade 1 or baseline.\r\n\r\n          3. Fit and planned for cystectomy (according to local guidelines).\r\n\r\n          4. Have received no prior systemic therapy for MIBC.\r\n\r\n          5. Must have post-TURBT site/lesion amenable for injection via cystoscopy (determined by\r\n             the Investigator).\r\n\r\n          6. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is\r\n             NOT required. This is an exception to the inclusion criterion outlined in the master\r\n             protocol.\r\n\r\n        Cohort B:\r\n\r\n          1. Unresectable locally advanced or metastatic bladder cancer\r\n\r\n               1. T4b, any N\r\n\r\n               2. Any T, N 2-3\r\n\r\n               3. Any T, any N, M1\r\n\r\n          2. Have received no more than one prior line of systemic therapy in the\r\n             unresectable/metastatic setting; systemic therapy given in the neoadjuvant or adjuvant\r\n             setting, where the last date of administration is  12 months prior to the date of\r\n             recurrence will be considered a line of therapy in the unresectable/metastatic\r\n             setting.\r\n\r\n          3. Must have lesion that is amenable to injection via cystoscopy of intact bladder (per\r\n             the Investigator) and at least one measured dimension  1 cm.\r\n\r\n          4. Must have at least 1 lesion amenable to biopsy a. The lesion must be safely accessible\r\n             as determined by the investigator and should not be located at sites that require\r\n             significant risk procedures to biopsy. Examples of sites considered to be of\r\n             significant risk include but are not limited to: biopsies of the brain, lung,\r\n             mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus,\r\n             stomach, or bowel wall.\r\n\r\n        Bladder Cancer Specific Exclusion Criteria:\r\n\r\n        Both Cohorts:\r\n\r\n          1. Warfarin is prohibited. Anticoagulant and antiplatelet medications will be managed by\r\n             the treating physician, per local institutional guidelines, to optimize the safety of\r\n             intratumoral injection of PVSRIPO.\r\n\r\n          2. Received prior treatment with a PD-1/L1 inhibitor for any malignancy including\r\n             early-stage bladder cancer.\r\n\r\n          3. Received prior treatment with an agent directed to another stimulatory or\r\n             co-inhibitory T-cell receptor.\r\n\r\n        Cohort A:\r\n\r\n        1. TURBT does not qualify as a major surgery/procedure or open biopsy (see exclusion\r\n        criterion in master protocol).\r\n\r\n        Head and Neck Cancer Specific Inclusion Criteria:\r\n\r\n        Both Cohorts\r\n\r\n          1. Must have an injectable lesion measuring  1.0 cm in at least one diameter that is\r\n             visible, palpable, or detectable by ultrasound. Lesions located in sites considered to\r\n             be of more significant risk for complications from PVSRIPO injection and associated\r\n             inflammation are not to be injected. Examples include:\r\n\r\n               1. Lesions located in the liver, lung, pancreas, bowel, and other visceral organs\r\n                  are not considered injectable.\r\n\r\n               2. Lesions encasing or immediately adjacent to major blood vessels including the\r\n                  carotid artery are not considered injectable.\r\n\r\n               3. Lesions that have been treated with curative levels of radiation and have not\r\n                  healed from radiation-associated toxicities are not considered injectable.\r\n\r\n          2. Documentation of p16-positive or p16-negative disease by CLIA/CAP-approved test to\r\n             determine HPV status of tumor for HNSCC of the oropharynx.\r\n\r\n               1. Note: If local results are not available, then a sample (tissue on microscopic\r\n                  slides, tissue block or a fresh tissue biopsy in formalin) should be sent to the\r\n                  central laboratory for analysis.\r\n\r\n               2. Note: Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV\r\n                  testing by p16 testing as by convention these tumor locations are assumed to be\r\n                  HPV negative.\r\n\r\n          3. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or new biopsy\r\n             if collection date of archival specimen > 6 months prior to Cycle 1 Day 1) with an\r\n             associated pathology report documenting the histology of the tumor type of interest\r\n             must be confirmed to be available to send to the Sponsor.\r\n\r\n               1. Must have a minimum of 15 unstained, freshly cut, serial sections from an FFPE\r\n                  tumor specimen (or FFPE block equivalent) available.\r\n\r\n               2. If fewer than 15 slides are available at baseline, the patient may still be\r\n                  eligible upon discussion with the Medical Monitor.\r\n\r\n          4. Must have at least 1 lesion amenable to biopsy\r\n\r\n             a. The lesion must be safely accessible as determined by the investigator and should\r\n             not be located at sites that require significant risk procedures to biopsy. Examples\r\n             of sites considered to be of significant risk include but are not limited to: biopsies\r\n             of the brain, lung, mediastinum, pancreas, or endoscopic procedures extending beyond\r\n             the esophagus, stomach, or bowel wall.\r\n\r\n          5. HIV positive patients are eligible to enroll provided the following criteria have been\r\n             met:\r\n\r\n               1. CD4+ T cell counts  350l/L\r\n\r\n               2. No history of AIDS-defining opportunistic infections within the last 12 months\r\n\r\n               3. Have been on established antiretroviral therapy (ART) for at least four weeks and\r\n                  have an HIV RNA viral load of < 400 copies/mL prior to the first dose of study\r\n                  drug NOTE: this criterion is an exception to Exclusion Criterion #10 in the\r\n                  master protocol (Section 4.2) stating patients with an active HIV infection are\r\n                  excluded from enrollment\r\n\r\n          6. Patients with a history of chronic HCV are eligible to enroll provided the following\r\n             criteria have been met:\r\n\r\n               1. Have completed curative antiviral treatment OR been on established antiviral\r\n                  therapy for HCV for at least 4 weeks prior to the first dose of study drug.\r\n\r\n               2. Have an HCV RNA viral load below the limit of quantification. NOTE: this\r\n                  criterion is an exception to Exclusion Criterion #10 in the master protocol\r\n                  (Section 4.2) stating patients with an active HCV infection are excluded from\r\n                  enrollment.\r\n\r\n          7. Patients with a history of HBV infection are eligible to enroll provided the following\r\n             criteria have been met:\r\n\r\n               1. On HBV prophylaxis for at least 1 week prior to first dose of study drug\r\n\r\n               2. Have an HBV DNA viral load below the lower limit of quantification. NOTE: this\r\n                  criterion is an exception to Exclusion Criterion #10 in the master protocol\r\n                  (Section 4.2) stating patients with an active HBV infection are excluded from\r\n                  enrollment.\r\n\r\n        Cohort C\r\n\r\n          1. Histologically- or cytologically-confirmed SCC of the oral cavity, oropharynx,\r\n             hypopharynx, or larynx\r\n\r\n             a. Histologically confirmed carcinoma of the nasopharynx, squamous cell carcinoma of\r\n             unknown primary, and salivary gland or non-squamous histologies (eg mucosal melanoma)\r\n             are not allowed\r\n\r\n          2. Clinical stage II-IVA disease where the primary and neck metastases are considered\r\n             resectable, and the intent of treatment is curative.\r\n\r\n               1. Oral cavity, p16 negative oropharynx, hypopharynx, larynx: T2-T3, N0; T1-T3,\r\n                  N1-N2; T4a, N0-N2\r\n\r\n               2. p16 positive oropharynx: T0-T2, N2-N3; T3, N0-N3; T4, N0-N3\r\n\r\n          3. No prior therapy (eg surgery, chemotherapy, radiation etc.) for the study cancer.\r\n             Note: if the study cancer is considered to be a second (or third etc) primary, any\r\n             treatment received to treat the first primary cancer is not exclusionary as long as\r\n             the first primary is considered to be \"cured\", i.e no evidence of disease related to\r\n             the first primary.\r\n\r\n             a. Systemic/intratumoral therapy  6 months prior to the first dose of study drug is\r\n             exclusionary.\r\n\r\n          4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is\r\n             NOT required. Note: This is an exception to Inclusion Criterion #4 (Section 4.2) in\r\n             the master protocol, which requires measurable disease.\r\n\r\n        Cohort D\r\n\r\n          1. Histologically- or cytologically-confirmed recurrent or metastatic (R/M) SCC of the\r\n             oral cavity, oropharynx, hypopharynx, or larynx that is not amenable to local therapy\r\n             with curative intent (ie surgery or radiation therapy with or without chemotherapy)\r\n\r\n             a. Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx,\r\n             squamous cell carcinoma of unknown primary, and salivary gland or non-squamous\r\n             histologies (eg mucosal melanoma) are not allowed\r\n\r\n          2. No prior systemic/intratumoral therapy in the R/M setting.\r\n\r\n             a. Systemic/intratumoral therapy for locally advanced disease which was completed  6\r\n             months prior to the first dose of study drug is exclusionary.\r\n\r\n          3. Tumor expression of PD-L1 with CPS 1 using the PD-L1 IHC 22C3 pharmDx test.\r\n\r\n        Head and Neck Cancer Specific Exclusion Criteria:\r\n\r\n        Both Cohorts\r\n\r\n          1. Patients requiring oxygen supplementation.\r\n\r\n          2. Patients whose anticoagulation or antiplatelet medications cannot be managed by local\r\n             institutional guidelines to accommodate the safe intratumoral injection of PVSRIPO, as\r\n             determined by the treating physician.\r\n      ","sponsor":"Istari Oncology, Inc.","sponsor_type":"Industry","conditions":"Solid Tumor|Bladder Cancer|Head and Neck Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: PVSRIPO","description":"PVSRIPO administered via intertumoral injection every 3 weeks"},{"intervention_type":"Biological","name":"Biological: Anti-PD-1 / L1","description":"Anti-PD-1 / L1 Therapy administered per package insert instructions."}],"outcomes":[{"outcome_type":"primary","measure":"Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE","time_frame":"24 months","description":"To evaluate the safety and tolerability of PVSRIPO administered as monotherapy and in combination with an anti-PD-1/L1 therapy."},{"outcome_type":"primary","measure":"Tumor Response measured by RECIST 1.1","time_frame":"24 months","description":"To evaluate the tumor response to PVSRIPO administered in combination with an anti-PD-1/L1 therapy."}]}
{"nct_id":"NCT04148742","start_date":"2021-08-31","phase":"Phase 1/Phase 2","enrollment":120,"brief_title":"Assessing an Oral Bruton Tyrosine Kinase Inhibitor, DZD9008 in Patients Who Have Non-Hodgkin B-cell Lymphoma (WU-KONG3)","official_title":"A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients With Non-Hodgkin B-cell Lymphoma","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Suspended","completion_date":"2023-07-31","last_update":"2021-06-11","description":"This study will treat patients with non-Hodgkin B-cell lymphoma who have relapsed from, refractory or intolerant to prior therapy. This study will help understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy.","other_id":"DZ2019B0001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion criteria:\r\n\r\n          -  Aged at least 18 years old.\r\n\r\n          -  Patients must be willing and able to participate in all required evaluations and\r\n             procedures.\r\n\r\n          -  Patients must be able to provide a signed written informed consent.\r\n\r\n          -  With documented histologically confirmed diagnosis of CLL/SLL, MCL or MZL and have\r\n             least 1 measurable site of disease. Subjects must have relapsed, or are refractory or\r\n             intolerant to >= 2 lines of prior therapy, and without preferred alternative treatment\r\n             as judged by investigator. For Part B, subjects should be either BTK inhibitor\r\n             treatment naive or intolerant to prior BTK inhibitor within 6 months on treatment.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.\r\n\r\n          -  Predicted life expectancy  12 weeks.\r\n\r\n          -  Adequate organ system functions.\r\n\r\n        Exclusion criteria:\r\n\r\n          -  Prior malignancy requires active treatment within 2 to 3 years.\r\n\r\n          -  A life-threatening illness, medical condition or organ system dysfunction.\r\n\r\n          -  Radiotherapy with a limited field of radiation for palliation within 1 week of the\r\n             screening.\r\n\r\n          -  Major surgery within 4 weeks before screening.\r\n\r\n          -  Prior treatment with any onco-immunotherapy within 4 weeks before screening.\r\n\r\n          -  Subjects require immediate cytoreduction.\r\n\r\n          -  Any history of Richter's transformation.\r\n\r\n          -  Central nervous system (CNS) involvement unless previous treated and asymptomatic.\r\n\r\n          -  Requires anticoagulation therapy with Warfarin, heparin.\r\n\r\n          -  Known history of human immunodeficiency virus (HIV); Positive Hepatitis B surface\r\n             antigen (HbsAg) or positive HCV antibodies; any other uncontrolled active systemic\r\n             infection.\r\n\r\n          -  Any of the following cardiac criteria: (1) mean resting corrected QT interval (QTcF) >\r\n             470 msec obtained from 3 electrocardiograms (ECGs). (2) prior history of atrial\r\n             fibrillation. (3) any factors that increase the risk of QTcF prolongation, such as\r\n             heart failure, hypokalemia, congenital long QT syndrome, family history of long QT\r\n             syndrome or unexplained sudden death under 40 years of age in first degree relatives\r\n             or any concomitant medication known to prolong the QT interval\r\n\r\n          -  History of stroke or intracranial haemorrhage.\r\n\r\n          -  Past medical history of interstitial lung disease, drug-induced interstitial lung\r\n             disease, radiation pneumonitis which required steroid treatment, or any evidence of\r\n             clinically active interstitial lung disease\r\n\r\n          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to\r\n             swallow the formulated product or previous significant bowel resection.\r\n\r\n          -  History of hypersensitivity.\r\n\r\n          -  Receiving (or unable to stop using) medications or herbal supplements known to be\r\n             potent inhibitors or inducers of CYP3A.\r\n\r\n          -  Grapefruit, grapefruit juice, and orange marmalade (made with Seville oranges) should\r\n             be excluded.\r\n\r\n          -  Women who are pregnant or breast feeding\r\n\r\n          -  Judgment by the investigator that the patient should not participate in the study if\r\n             the patient is unlikely to comply with study procedures, restrictions and requirements\r\n\r\n          -  Previous allogenic bone marrow transplant.\r\n      ","sponsor":"Dizal Pharmaceuticals","sponsor_type":"Industry","conditions":"Non-Hodgkin's B-cell Lymphoma","interventions":[{"intervention_type":"Drug","name":"Drug: DZD9008","description":"Daily dose of DZD9008, except for cycle 0 of Part A, in which a single dose of DZD9008 is administrated. Starting dose of DZD9008 is 50 mg once daily. If tolerated, subsequent cohorts will test increasing doses of DZD9008."}],"outcomes":[{"outcome_type":"primary","measure":"Part A: Incidence of Treatment-Emergent Adverse Events","time_frame":"Through study completion, an average of 1.5 years","description":"Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0"},{"outcome_type":"primary","measure":"Part B: objective response rate (ORR)","time_frame":"Through study completion, an average of 1.5 years"},{"outcome_type":"secondary","measure":"Maximum Plasma DZD9008 concentration","time_frame":"up to 16 weeks"},{"outcome_type":"secondary","measure":"Plasma DZD9008 concentration- Area Under the Curve","time_frame":"up to 16 weeks"}]}
{"nct_id":"NCT04961996","start_date":"2021-08-27","phase":"Phase 3","enrollment":4100,"brief_title":"A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer)","official_title":"A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Patients With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer","primary_completion_date":"2025-12-19","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2033-11-21","last_update":"2021-09-05","description":"This is a Phase III, global, randomized, open-label, multicenter, study evaluating the efficacy and safety of adjuvant giredestrant compared with endocrine therapy of physician's choice in participants with medium- and high-risk Stage I-III histologically confirmed estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.","other_id":"GO42784","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Documented estrogen receptor (ER)-positive and HER2-negative breast tumor, as assessed\r\n             locally on a primary disease specimen\r\n\r\n          -  Participants who have multicentric (the presence of two of more tumor foci within\r\n             different quadrants of the same breast) and/or multifocal (the presence of two or more\r\n             tumor foci within a single quadrant of the breast) breast cancer are also eligible if\r\n             all examined tumors meet pathologic criteria for ER positivity and HER2 negativity\r\n\r\n          -  Participants must have undergone definitive surgery of the primary breast tumor(s).\r\n\r\n          -  Participants who received or will be receiving adjuvant chemotherapy must have\r\n             completed adjuvant chemotherapy prior to randomization. Participants may also have\r\n             received neoadjuvant chemotherapy. A washout period of at least 21 days is required\r\n             between last adjuvant chemotherapy dose and randomization.\r\n\r\n          -  Resolution of all acute toxic effects of prior anti-cancer therapy or surgical\r\n             procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade 2 peripheral\r\n             neuropathy, arthralgia or other toxicities not considered a safety risk for the\r\n             participant per the investigator's judgment)\r\n\r\n          -  Participants have received (neo)adjuvant chemotherapy and/or had surgery and had no\r\n             prior endocrine therapy are eligible, provided that they are enrolled within 12 months\r\n             following definitive breast cancer surgery\r\n\r\n          -  Participants who have confirmed availability of an untreated primary breast tumor\r\n             tissue specimen suitable for biomarker testing (i.e., representative archived\r\n             formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or 15-20 slides\r\n             containing unstained, freshly cut, serial sections), with associated de-identified\r\n             pathology report is required. Although 15-20 slides are preferred, if only 10-14\r\n             slides are available, the individual may still be eligible for the study.\r\n\r\n          -  Participants with node-positive and node-negative disease are eligible provided they\r\n             meet additional risk criteria as defined in the protocol\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2\r\n\r\n          -  Able and willing to swallow, retain, and absorb oral medication\r\n\r\n          -  Adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within\r\n             9 days after the final dose of giredestrant, or within the time period specified per\r\n             local prescribing guidelines after the final dose of the endocrine therapy of\r\n             physician's choice\r\n\r\n          -  Received treatment with investigational therapy within 28 days prior to initiation of\r\n             study treatment or is currently enrolled in any other type of medical research judged\r\n             by the sponsor not to be scientifically or medically compatible with this study\r\n\r\n          -  Receiving or planning to receive a CDK4/6i as adjuvant therapy\r\n\r\n          -  Active cardiac disease or history of cardiac dysfunction\r\n\r\n          -  Diagnosed with Stage IV breast cancer\r\n\r\n          -  A history of any prior (ipsilateral and/or contralateral) invasive breast cancer or\r\n             ductal carcinoma in situ (DCIS). Participants with a history of contralateral DCIS\r\n             treated by only local regional therapy at any time may be eligible.\r\n\r\n          -  A history of any other malignancy within 3 years prior to screening, except for\r\n             appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, or\r\n             Stage I uterine cancer\r\n\r\n          -  Any prior endocrine treatment with selective ER downregulators or degraders or\r\n             aromatase inhibitors\r\n\r\n          -  Clinically significant liver disease consistent with Child-Pugh Class B or C,\r\n             including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]),\r\n             current alcohol abuse, cirrhosis, or positive test for viral hepatitis\r\n\r\n          -  Known allergy or hypersensitivity to any of the study drugs or any of their excipients\r\n\r\n          -  Pre- and perimenopausal participants or male participants who have a known\r\n             hypersensitivity to LHRH agonists\r\n\r\n          -  A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism\r\n\r\n          -  A major surgical procedure unrelated to breast cancer within 28 days prior to\r\n             randomization\r\n\r\n          -  A serious infection requiring oral or IV antibiotics within 14 days prior to screening\r\n             or other clinically significant infection (e.g., COVID-19) within 14 days prior to\r\n             screening\r\n\r\n          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the\r\n             investigator's judgment, precludes an individual's safe participation in and\r\n             completion of the study\r\n\r\n          -  Unable or unwilling to comply with the requirements of the protocol in the opinion of\r\n             the investigator\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Early Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Giredestrant","description":"Giredestrant 30 milligrams (mg) will be administered orally once a day (QD) on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first)."},{"intervention_type":"Drug","name":"Drug: Endocrine Therapy of Physician's Choice","description":"The endocrine therapy of physician's choice (TPC) is limited to tamoxifen or one of the specified third generation aromatase inhibitors: letrozole, anastrozole, or exemestane. Participants will receive TPC daily on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first). Continuing TPC after 5 years is at the discretion of the investigator and per local standard of care. Dose administration of TPC should be performed in accordance with the local prescribing information for the respective product."},{"intervention_type":"Drug","name":"Drug: LHRH Agonist","description":"A luteinizing hormone-releasing hormone (LHRH) agonist will be administered to male participants and premenopausal/perimenopausal participants according to local prescribing information. The investigator may determine and supply the appropriate LHRH agonist locally approved for use in breast cancer."}],"outcomes":[{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"From randomization to death from any cause (up to 10 years)"},{"outcome_type":"secondary","measure":"Locoregional Recurrence-Free Interval (LRRFI)","time_frame":"From randomization to first occurrence of a LRRFI event (up to 10 years)"},{"outcome_type":"secondary","measure":"Disease-Free Survival (DFS)","time_frame":"From randomization to first occurrence of a DFS event (up to 10 years)"},{"outcome_type":"secondary","measure":"Distant Recurrence-Free Interval (DRFI)","time_frame":"From randomization to first occurrence of a DFRI event (up to 10 years)"},{"outcome_type":"primary","measure":"Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers","time_frame":"From randomization to first occurrence of an IDFS event (up to 10 years)"},{"outcome_type":"secondary","measure":"Invasive Disease-Free Survival (IDFS), Including Second Primary Non-Breast Cancers","time_frame":"From randomization to first occurrence of an IDFS event (up to 10 years)"},{"outcome_type":"secondary","measure":"Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the EQ 5D-5L Index-Based Score at Specified Timepoints","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the EQ 5D-5L Visual Analogue Scale (VAS) Score at Specified Timepoints","time_frame":"Baseline (Cycle 1) and Cycles 2, 3, 6, 9, 12, and every 3 cycles thereafter (1 cycle is 28 days) until end of treatment, then once every 6 months during post-treatment follow-up (up to 10 years)"},{"outcome_type":"secondary","measure":"Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)","time_frame":"From start of treatment until 28 days after the final dose of study treatment (up to 5 years)"},{"outcome_type":"secondary","measure":"Plasma Concentrations of Giredestrant at Specified Timepoints","time_frame":"Predose and 3 hours postdose on Day 1 of Cycles 1 and 2, and predose on Day 1 of Cycles 3 and 6 (1 cycle is 28 days)"}]}
{"nct_id":"NCT05005273","start_date":"2021-08-25","phase":"Phase 2","enrollment":224,"brief_title":"A Study to Assess BMS-986207 in Combination With Nivolumab and Ipilimumab as First-line Treatment for Participants With Stage IV Non-Small Cell Lung Cancer","official_title":"A Phase 2 Randomized Double-blind Study of BMS-986207 in Combination With Nivolumab and Ipilimumab as First-line Treatment for Participants With Stage IV Non-Small Cell Lung Cancer","primary_completion_date":"2024-02-22","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-05-30","last_update":"2021-08-13","description":"The purpose of this study is to determine the safety and efficacy of BMS-986207 in combination with nivolumab and ipilimumab as first-line treatment for participants with stage IV non-small cell lung cancer (NSCLC).","other_id":"CA020-016","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit: www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed metastatic 1L Stage IV non-small cell lung cancer (NSCLC) of\r\n             squamous or nonsquamous histology\r\n\r\n          -  No prior systemic anti-cancer treatment given as primary therapy for advanced or\r\n             metastatic NSCLC\r\n\r\n          -  Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1\r\n\r\n          -  A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or a minimum of 20\r\n             unstained slides of tumor tissue obtained during screening or prior to enrollment\r\n\r\n          -  Life expectancy of at least 3 months at the time of first dose\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participants with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase\r\n             (ALK), or c-ros oncogene 1 (ROS-1) mutations which are sensitive to available targeted\r\n             inhibitor therapy. Participants with nonsquamous histology and unknown EGFR, ALK, or\r\n             ROS-1 status are also excluded\r\n\r\n          -  Participants with known B-rapidly accelerated fibrosarcoma proto-oncogene (BRAF) V600E\r\n             mutations that are sensitive to available targeted inhibitor therapy. Participants\r\n             with unknown or indeterminate BRAF mutation status are eligible.\r\n\r\n          -  Untreated central nervous system metastases\r\n\r\n          -  Leptomeningeal metastases (carcinomatous meningitis)\r\n\r\n          -  Concurrent malignancy requiring treatment\r\n\r\n          -  Active, known, or suspected autoimmune disease\r\n\r\n          -  Interstitial lung disease\r\n\r\n          -  Uncontrolled or significant cardiovascular disease\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer","interventions":[{"intervention_type":"Other","name":"Other: Placebo","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Nivolumab","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Ipilimumab","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: BMS-986207","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Incidence of deaths","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Incidence of adverse events (AEs) meeting protocol-defined dose-limiting toxicity (DLT) criteria","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Incidence of AEs","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Incidence of treatment-related adverse events (TRAEs)","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Incidence of serious adverse events (SAEs)","time_frame":"Up to 4 years","description":"Part 1"},{"outcome_type":"primary","measure":"Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR)","time_frame":"Up to 25 months","description":"Part 2"},{"outcome_type":"secondary","measure":"PFS based on RECIST v1.1 by BICR","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"PFS based on RECIST v1.1 by Investigator's assessment","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"Incidence of AEs","time_frame":"Up to 4 years","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of SAEs","time_frame":"Up to 4 years","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 4 years","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of deaths","time_frame":"Up to 4 years","description":"Part 2"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) based on RECIST v1.1 by BICR","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"ORR based on RECIST v1.1 by Investigator's assessment","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) based on RECIST v1.1 by BICR","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"DOR based on RECIST v1.1 by Investigator's assessment","time_frame":"Up to 25 months","description":"Parts 1 & 2"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to 30 months","description":"Parts 1 & 2"}]}
{"nct_id":"NCT04915755","start_date":"2021-08-25","phase":"Phase 3","enrollment":800,"brief_title":"Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Either Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease","official_title":"A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants With Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer With Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy (ZEST)","primary_completion_date":"2025-02-05","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2029-08-24","last_update":"2021-06-07","description":"This is a multicenter, multi-cohort, phase 3, double-blinded, placebo-controlled study to assess the efficacy and safety of Niraparib in participants with either tumor mutation in the BRCA gene (tBRCAmut) HER2- breast cancer (Independent of hormone receptor [HR] status, including HR positive [+] and TNBC) or tumor BRCA wild type (tBRCAwt) TNBC with molecular disease based on the presence of circulating tumor Deoxyribonucleic acid (ctDNA) following surgery or completion of adjuvant therapy. Participants who have completed definitive therapy at any time in the past are eligible for ctDNA monitoring and potential enrollment onto the trial.","other_id":"213831","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","intervention_model_description":"This is a multicenter, multi-cohort, phase 3, double-blinded, placebo-controlled study","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Stage I to III breast cancer with surgical resection of the primary tumor that is\r\n             confirmed to be either: TNBC, irrespective of BRCA status or HR+/HER2- breast cancer\r\n             with a known and documented tBRCA mutation.\r\n\r\n          -  Completed prior standard therapy for curative intent including all of the following,\r\n             if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant\r\n             chemotherapy.\r\n\r\n          -  Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy,\r\n             if indicated, for at least 3 months prior to enrollment. Ovarian suppression, if\r\n             indicated, must also have been started at least 3 months prior to enrollment.\r\n\r\n          -  Detectable ctDNA as measured by central Signatera testing.\r\n\r\n          -  An archival tumor tissue specimen of the primary tumor sufficient in quality and\r\n             quantity for ctDNA assay design and tBRCA and Homologous recombination deficiency\r\n             (HRD).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior treatment with a Poly Adenosine-diphosphate Ribose Polymerase (PARP) inhibitor.\r\n\r\n          -  Current treatment with a Cyclin-dependent kinase (CDK)4/6 inhibitor or endocrine\r\n             therapy other than anastrozole, letrozole, exemestane, and tamoxifen.\r\n\r\n          -  Participants have any sign of metastasis or local recurrence after comprehensive\r\n             assessment conducted per protocol.\r\n\r\n          -  Participants have shown no definitive response to preoperative chemotherapy by\r\n             pathologic or radiographic evaluation, in cases where preoperative chemotherapy was\r\n             administered.\r\n\r\n          -  Participants have received live vaccine within 30 days of planned start of study\r\n             randomization.\r\n\r\n          -  Participants have a second primary malignancy. Exceptions are the following: (a)\r\n             Adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the\r\n             cervix, Ductal carcinoma in situ (DCIS) of the breast, Stage I Grade 1 endometrial\r\n             carcinoma. (b) Other solid tumors and lymphomas (without bone marrow involvement)\r\n             diagnosed greater than equal to (>=) 5 years prior to randomization and treated with\r\n             no evidence of disease recurrence and for whom no more than 1 line of chemotherapy was\r\n             applied.\r\n\r\n          -  Participant is pregnant, breastfeeding, or expecting to conceive children while\r\n             receiving study treatment and/or for up to 180 days after the last dose of study\r\n             treatment.\r\n\r\n          -  Participants have a history of human immunodeficiency virus (HIV) disease.\r\n\r\n          -  Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid\r\n             leukemia (AML).\r\n      ","sponsor":"GlaxoSmithKline","sponsor_type":"Industry","conditions":"Neoplasms, Breast","interventions":[{"intervention_type":"Drug","name":"Drug: Niraparib","description":"Niraparib will be administered."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Matching placebo will be administered"}],"outcomes":[{"outcome_type":"primary","measure":"Disease-free survival (DFS)","time_frame":"Up to 4 years","description":"DFS is defined as the time until disease recurrence, measured from the time of randomization to the earliest date of assessment of disease recurrence or death by any cause."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 8 years","description":"OS is defined as the time from randomization to the date of death by any cause."},{"outcome_type":"secondary","measure":"Time to progression on next anticancer therapy (TTP)","time_frame":"Up to 8 years","description":"Time to progression is defined as the time from randomization to the earliest progression event subsequent to that used for the primary variable DFS or death by any cause."},{"outcome_type":"secondary","measure":"Distant recurrence-free survival (DRFS)","time_frame":"Up to 4 years","description":"DRFS is defined as the time from randomization to the first detection of distant metastasis or death by any cause."},{"outcome_type":"secondary","measure":"Number of participants with Treatment-emergent adverse events (TEAEs), Serious adverse events (SAEs), TEAEs leading to death, and AEs leading to discontinuation","time_frame":"Up to 8 years","description":"All TEAEs, SAEs, TEAEs leading to death, and AEs leading to discontinuation will be collected."},{"outcome_type":"secondary","measure":"Number of participants with clinically significant changes in laboratory parameters, vital signs, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications","time_frame":"Up to 8 years","description":"Number of participants with clinically significant changes in laboratory parameters, vital signs, ECOG status, physical examination and use of concomitant examinations will be evaluated"},{"outcome_type":"secondary","measure":"Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) (Scores on a scale)","time_frame":"Baseline (Day 1) and up to 8 years","description":"EORTC-QLQC 30 is a 30 item questionnaire developed to assess the quality of life of cancer participants."},{"outcome_type":"secondary","measure":"Change from Baseline in the Functional Assessment of Cancer Therapy - General Population(FACT-GP5) (Scores on a scale)","time_frame":"Baseline (Day 1) and up to 8 years","description":"The FACT-GP5 item is a single item from the FACT-G, which assesses how bothersome the side effects of treatment are for participants with cancer."},{"outcome_type":"secondary","measure":"Patient reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (Scores on a scale)","time_frame":"Up to 8 years","description":"The PRO-CTCAE is a PRO measure developed to evaluate symptomatic toxicity in participants with cancer."}]}
{"nct_id":"NCT04995523","start_date":"2021-08-22","phase":"Phase 1/Phase 2","enrollment":147,"brief_title":"A Study to Assess the Safety and Efficacy of AZD2936 in Participants With Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)","official_title":"A Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic Non-small Cell Lung Cancer","primary_completion_date":"2023-11-14","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-11-14","last_update":"2021-08-09","description":"This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody, AZD2936 is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.","other_id":"D7020C00001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"The study includes 4 parts: Part A (dose escalation) and Parts B-D (dose expansion).","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Written informed consent\r\n\r\n          -  Aged 18 or above\r\n\r\n          -  Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to\r\n             curative surgery or radiation.\r\n\r\n          -  Documented PD-L1 expression by PD-L1 IHC per local report.\r\n\r\n          -  Confirmed progression during treatment with a CPI-including regimen.\r\n\r\n          -  ECOG performance status of 0 or 1 at enrolment.\r\n\r\n          -  Life expectancy of  12 weeks at enrolment.\r\n\r\n          -  Adequate bone marrow, liver and kidney function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma\r\n             kinase (ALK) fusion\r\n\r\n          -  Documented test result for any other known genomic alteration for which a targeted\r\n             therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions,\r\n             BRAF, V600E mutation)\r\n\r\n          -  Previous treatment with an anti-TIGIT therapy\r\n\r\n          -  Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal\r\n             therapy for cancer treatment.\r\n\r\n          -  Primary or secondary resistance after treatment with 2 or more regimens including a\r\n             CPI.\r\n\r\n          -  Symptomatic central nervous system (CNS) metastasis.\r\n\r\n          -  Thromboembolic event within 3 months prior to enrolment.\r\n\r\n          -  Other invasive malignancy within 2 years prior to screening.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Non-Small-Cell Lung Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: AZD2936","description":"Anti-TIGIT/Anti-PD-1 Bispecific Antibody"}],"outcomes":[{"outcome_type":"secondary","measure":"Incidence of anti-drug antibodies (ADA) against AZD2936 in serum","time_frame":"From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"Immunogenicity of AZD2936"},{"outcome_type":"primary","measure":"Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters","time_frame":"Part A, B, C: From the time of informed consent until 90 days after the last dose of AZD2936","description":"A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness."},{"outcome_type":"primary","measure":"Rate of AZD2936 discontinuation due to toxicity","time_frame":"Part A, B, C: From first dose to the last dose of AZD2936 (an average of 6 months)","description":"Percentage of participants with AEs leading to discontinuation of AZD2936"},{"outcome_type":"primary","measure":"Objective Response Rate (ORR)","time_frame":"Part B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years)","description":"Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1"},{"outcome_type":"secondary","measure":"ORR","time_frame":"Part A: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years)","description":"Percentage of participants with a confirmed CR or PR according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years)","description":"Percentage of participants who have a best objective response of confirmed CR or PR or who have SD lasting for at least a certain time of period after start of treatment"},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years)","description":"The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression"},{"outcome_type":"secondary","measure":"Durable response rate (DRR)","time_frame":"Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years)","description":"The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"Part B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression. (approximately 2 years)","description":"The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression"},{"outcome_type":"secondary","measure":"Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood","time_frame":"Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"Evaluation of the target engagement of AZD2936 in peripheral blood"},{"outcome_type":"secondary","measure":"PK of AZD2936: Maximum plasma concentration of the study drug (Cmax)","time_frame":"From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"Maximum observed plasma concentration of AZD2936"},{"outcome_type":"secondary","measure":"PK of AZD2936: Area under the concentration-time curve (AUC)","time_frame":"From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"Area under the plasma concentration-time curve"},{"outcome_type":"secondary","measure":"PK of AZD2936: Clearance","time_frame":"From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time."},{"outcome_type":"secondary","measure":"PK of AZD2936: Terminal elimination half-life (t 1/2)","time_frame":"From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C.","description":"Terminal elimination half life"}]}
{"nct_id":"NCT04989387","start_date":"2021-08-21","phase":"Phase 1","enrollment":230,"brief_title":"Study of INCA 0186 in Subjects With Advanced Solid Tumors","official_title":"A Phase 1, Open-Label, Multicenter Study of INCA00186 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors","primary_completion_date":"2024-05-21","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-05-21","last_update":"2021-08-04","description":"This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCA00186 when given alone or in combination with INCB106385 and/or retifanlimab in participants with specific advanced solid tumors; squamous cell carcinoma of the head and neck (SCCHN) and specified gastrointestinal (GI) malignancies have been selected as indications of interest for this study. Participants with CD8 T-cell-positive tumors will be selected as these tumors are more likely to respond to immunotherapy.","other_id":"INCA 0186-101","allocation":"Non-Randomized","intervention_model":"Factorial Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":90,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Ability to comprehend and willingness to sign a written ICF for the study.\r\n\r\n          -  Male or female participant aged 18 years or older inclusive at the time of signing the\r\n             ICF.\r\n\r\n          -  Must be willing and able to conform to and comply with all Protocol requirements\r\n\r\n          -  Willingness to undergo pre- and on-treatment tumor biopsy.\r\n\r\n          -  Have CD8 T-cell-positive tumors\r\n\r\n          -  ECOG performance status 0 or 1.\r\n\r\n          -  Measurable disease according to RECIST v1.1.\r\n\r\n          -  Participants with SCCHN: Participants with histologically or cytologically confirmed\r\n             squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx not\r\n             amenable to local therapy with curative intent (surgery or radiation with or without\r\n             chemotherapy).\r\n\r\n          -  Participants with specified GI malignancies: Histologically or cytologically confirmed\r\n             advanced or metastatic colorectal (CRC), gastric/gastroesophageal junction (GEJ)\r\n             cancer, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), or\r\n             squamous carcinoma of the anal canal (SCAC).\r\n\r\n          -  Participants should have disease progression after treatment with available therapies,\r\n             including anti-PD-(L)1 therapy (if applicable), that are known to confer clinical\r\n             benefit or who are intolerant to or ineligible for standard treatment. Prior\r\n             anti-PD-(L)1 therapy should not have been discontinued because of intolerance.\r\n\r\n          -  For participants to be enrolled in cohorts including INCB106385: The ability to\r\n             swallow oral medication.\r\n\r\n          -  Willingness to avoid pregnancy or fathering children\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Clinically significant cardiac disease, unstable angina, acute myocardial infarction\r\n             within 6 months of Cycle 1 Day 1, and New York Heart Association Class III or IV\r\n             congestive heart failure.\r\n\r\n          -  History or presence of an ECG abnormality that, in the investigator's opinion, is\r\n             clinically meaningful.\r\n\r\n          -  Known active CNS metastases and/or carcinomatous meningitis.\r\n\r\n          -  Participants who have active or inactive autoimmune disease or syndrome (eg,\r\n             rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory\r\n             bowel disease) that has required systemic treatment in the past 2 years or who are\r\n             receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of\r\n             disease modifying agents, corticosteroids, or immunosuppressive drugs).\r\n\r\n          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses\r\n             > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive\r\n             therapy within 7 days before the first dose of study treatment.\r\n\r\n          -  Known additional malignancy that is progressing or requires active treatment, or\r\n             history of other malignancy within 2 years of the first dose of study treatment with\r\n             the exception of cured basal cell or squamous cell carcinoma of the skin, superficial\r\n             bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or\r\n             other noninvasive or indolent malignancy, or cancers from which the participant has\r\n             been disease free > 1 year after treatment with curative intent.\r\n\r\n          -  Participants with protocol specified exclusionary hematology, hepatic, renal and\r\n             coagulation laboratory values at screening.\r\n\r\n        Has not recovered to  Grade 1 from toxic effects of prior therapy (including prior\r\n        immunotherapy) and/or complications from prior surgical intervention before starting study\r\n        treatment.\r\n\r\n          -  Evidence of interstitial lung disease, history of interstitial lung disease, or active\r\n             noninfectious pneumonitis.\r\n\r\n          -  Immune-related toxicity during prior immune therapy for which permanent\r\n             discontinuation of therapy is recommended, OR any immune-related toxicity requiring\r\n             intensive or prolonged immunosuppression to manage.\r\n\r\n          -  Prior treatment with any adenosine pathway targeting drugs.\r\n\r\n          -  Any prior chemotherapy, biological therapy, or targeted therapy to treat the\r\n             participant's disease within 5 half-lives or 28 days (whichever is shorter) before the\r\n             first dose of study treatment.\r\n\r\n          -  Any prior radiation therapy within 28 days before the first dose of study treatment.\r\n\r\n          -  Undergoing treatment with another investigational medication or having been treated\r\n             with an investigational medication within 5 half-lives or 28 days (whichever is\r\n             shorter) before the first dose of study treatment.\r\n\r\n          -  For participants to be enrolled in cohorts including INCB106385: concomitant treatment\r\n             with strong CYP3A4 inhibitors or inducers.\r\n\r\n          -  Receipt of a live virus vaccine within 30 days of the first dose of study treatment.\r\n\r\n          -  Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week\r\n             of the first dose of study treatment.\r\n\r\n          -  Known or suspected SARS-CoV-2 infection at the time of enrollment.\r\n\r\n          -  Active HBV or HCV infection that requires treatment. HBV-DNA and HCV-RNA must be\r\n             undetectable. Participants who have cleared a prior HBV infection (defined as HBsAg\r\n             negative, HBsAg antibody positive, and anti-HBc antibody positive) are eligible for\r\n             the study.\r\n\r\n          -  Known history of HIV (HIV 1/2 antibodies).\r\n\r\n          -  History of organ transplant, including allogeneic stem-cell transplantation or CAR-T\r\n             cell therapy.\r\n\r\n          -  Known hypersensitivity or severe reaction to any component of study drug(s) or\r\n             formulation components.\r\n\r\n          -  For participants to be enrolled in cohorts including INCB106385: Inability to swallow\r\n             food or any concomitant condition of the upper GI tract that precludes administration\r\n             of oral medications.\r\n\r\n          -  Is pregnant or breastfeeding.\r\n\r\n          -  Any condition that would, in the investigator's judgment, interfere with full\r\n             participation in the study, including administration of study treatment and attending\r\n             required study visits; pose a significant risk to the participant; or interfere with\r\n             interpretation of study data.\r\n\r\n          -  The following participants are excluded in France: vulnerable populations according to\r\n             article L.1121-6 of the French Public Health Code and adults under legal protection or\r\n             who are unable to express their consent per article L.1121-8 of the French Public\r\n             Health Code.\r\n      ","sponsor":"Incyte Corporation","sponsor_type":"Industry","conditions":"Advanced Solid Tumors|Squamous Cell Carcinoma of the Head and Neck (SCCHN)|Gastrointestinal (GI) Malignancies","interventions":[{"intervention_type":"Drug","name":"Drug: INCA00186","description":"INCA00186 will be administered every 2 weeks or 4 weeks as per protocol"},{"intervention_type":"Drug","name":"Drug: Retifanlimab","description":"Retifanlimab will be administered every 4 weeks as per protocol"},{"intervention_type":"Drug","name":"Drug: INCB106385","description":"INCB106385 will be administered orally once or twice a day."}],"outcomes":[{"outcome_type":"secondary","measure":"Determination of PK parameter half-life (t1/2) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"primary","measure":"Evaluation of the safety and tolerability of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by the number of participants with adverse eventsductions and withdrawal of treatment due to AEs","time_frame":"90 days after study completion totaling up to 27 months"},{"outcome_type":"primary","measure":"Evaluation of Dose-Limiting Toxicity (DLTs) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety events during treatment","time_frame":"90 days after study completion totaling up to 27 months"},{"outcome_type":"primary","measure":"Evaluation of Recommended Dose for Expansion (RDE) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety, PK and PD data","time_frame":"90 days after study completion totaling up to 27 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter Maximum Observed Plasma Concentration (Cmax) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter of Time to Maximum Plasma Concentration (tmax) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter of concentration at the end of the dosing interval (Ctau) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter of area under the plasma or serum concentration-time curve (AUC) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter of total clearance (CL) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Determination of PK parameter of volume of distribution (Vz) for INCA00186","time_frame":"Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months"},{"outcome_type":"secondary","measure":"Intratumoral effect of INCA0186 on CD73 enzymatic activity","time_frame":"2 biopsy samples will be taken: pre-treatment and on-treatment on Cycle 1 Day 22 (for every 2 week INCA00186 dosing group) or Cycle 2 Day 8 (for every 4 week INCA00186 dosing group); each cycle is 28 days; sampling will be taken within 2 months."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by radiographic disease assessment","time_frame":"Baseline through end of study up, to 24 months"},{"outcome_type":"secondary","measure":"Disease Control Response (DCR) determined by radiographic disease assessment","time_frame":"Baseline through end of study, up to 24 months"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) from earliest date of disease response until earliest date of disease progression as determined by radiographic disease assessment, or death if occurring sooner than progression","time_frame":"Baseline through end of study, up to 24 months"}]}
{"nct_id":"NCT04991129","start_date":"2021-08-20","phase":"Phase 1","enrollment":108,"brief_title":"The Safety and Efficacy of Multiple-dose of WJ01024 in Subject With Advanced Cancer","official_title":"A Dose Escalation and Dose Expansion Study of WJ01024 to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy for Patients With Advanced Cancer","primary_completion_date":"2023-07-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-30","last_update":"2021-08-05","description":"A clinical study of WJ01024 in subjects with advanced cancer in China, to evaluate the safety, tolerability, PK and efficacy of WJ01024. This study includes a dose escalation part and a dose expansion part. Patients receive WJ01024 on Day 1 and Day 3 of each week, 4 weeks as a cycle, until disease progression, or intolerable toxicity , withdrawal of consent, or end of the study, whichever occurs first.","other_id":"JJSW-01","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Sequential","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":70,"population":"","criteria":"\n        \"Inclusion criteria\r\n\r\n          1. Patients with advanced malignant neoplasms definitively diagnosed by pathology and/or\r\n             cytology who have failed to respond to conventional treatment or are lacking effective\r\n             treatment;\r\n\r\n          2. For patients with solid tumors, there should be evaluable or measurable tumor lesions\r\n             according to RECIST 1.1 criteria (not for dose-climbing phase);\r\n\r\n          3. Males and females  18 and  70 years of age,ECOG performance status of 0~1;\r\n\r\n          4. Life expectancy 3 months;\r\n\r\n          5. The functions of the major organs were basically normal, and the following laboratory\r\n             tests were performed within 7 days before the first administration of the study drug\r\n             (no blood transfusion or colony-stimulating factor was administered within 14 days\r\n             before the examination);\r\n\r\n          6. For premenopausal women who are likely to have children, a pregnancy test must be\r\n             performed within 7 days before the first use of the study drug. The blood pregnancy\r\n             test must be negative and must be non-lactating.All enrolled patients (both male and\r\n             female) should take adequate barrier contraception throughout the treatment period and\r\n             3 months after the end of treatment;\r\n\r\n          7. Voluntary participant in this drug clinical trial, able to understand and sign the\r\n             informed consent.\r\n\r\n        Exclusion criteria\r\n\r\n          1. Pregnant or lactating women;\r\n\r\n          2. Suffer from other serious complications (such as uncontrolled infection, myocardial\r\n             infarction within 6 months, uncontrolled hypertension and thromboembolic disease);\r\n\r\n          3. There was active graft rejection at the time of enrollment (after allogeneic stem cell\r\n             transplantation);\r\n\r\n          4. Who is not suitable for the study after laboratory examination (blood routine, urine\r\n             routine, blood biochemical, blood coagulation function) or as judged by the study\r\n             physician;\r\n\r\n          5.  Grade 2 toxicity after previous treatment;\r\n\r\n          6. Patients with grade 2 or more neuropathy;\r\n\r\n          7. A person suffering from an uncontrollable mental illness;\r\n\r\n          8. Have a history of drug abuse or urine drug screening positive;\r\n\r\n          9. Heart disease: New York heart association (NYHA) > class II congestive heart failure,\r\n             unstable angina (resting angina symptoms), new angina (within 6 months before entering\r\n             the study), into the group of the first six months of myocardial infarction, or need\r\n             anti-arrhythmic treatment for arrhythmia (allows the use of beta blockers, calcium\r\n             channel blockers and digoxin);\r\n\r\n         10. Alcoholics or those who consume more than 28 units of alcohol per week (1 unit = 285\r\n             mL beer or 25 mL spirits (40%v/v) or 1 glass [100ml] of wine);\r\n\r\n         11. Patients with active hepatitis B, hepatitis C, HIV (+) and syphilis antibody\r\n             (+);Patients with HBsAg or core antibody (HBcAb) positivity need to be tested for\r\n             HBV-DNA, and HBV-DNA is lower than the upper limit of normal to be enrolled.Patients\r\n             with hepatitis C virus antibody (HCV Ab) positive should be tested for HCV RNA, and\r\n             those below the upper limit of normal can be enrolled.\r\n\r\n         12. Requiring long-term corticosteroids or other immunosuppressive therapy, such as those\r\n             who have had organ transplants;\r\n\r\n         13. Other conditions considered ineligible by the investigator.\"\r\n      ","sponsor":"Suzhou Junjing BioSciences Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Hematologic Malignancies|Advanced Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: WJ01024","description":"5mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"10mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"20mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"40mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"60mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"80mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"100mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"120mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"140mg: WJ01024, Q4W, twice per week"},{"intervention_type":"Drug","name":"Drug: WJ01024","description":"1600mg: WJ01024, Q4W, twice per week"}],"outcomes":[{"outcome_type":"primary","measure":"The incidence of adverse events (AE) and serious adverse events (SAE) were assessed","time_frame":"2 years","description":"Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in vital signs, electrocardiogram, and laboratory tests"},{"outcome_type":"secondary","measure":"ORR","time_frame":"2 years","description":"DLT, MTD, RP2D, Number of participants and severity with treatment-related Adverse events as assessed by CTCAE V5.0"},{"outcome_type":"secondary","measure":"DOR","time_frame":"2 years","description":"Duration of Response"},{"outcome_type":"secondary","measure":"DCR","time_frame":"2 years","description":"Disease Control Rate"},{"outcome_type":"secondary","measure":"PFS","time_frame":"2 years","description":"Progression-free survival"},{"outcome_type":"secondary","measure":"Cmax","time_frame":"2 years","description":"Maximum Plasma Concentration"},{"outcome_type":"secondary","measure":"Tmax","time_frame":"2 years","description":"Time to Cmax"},{"outcome_type":"secondary","measure":"AUC0-t","time_frame":"2 years","description":"Area under the concentration versus time curve from time 0 to the last measurable concentration"},{"outcome_type":"secondary","measure":"AUC0-inf","time_frame":"2 years","description":"AUC from time 0 to infinity"},{"outcome_type":"secondary","measure":"Kel","time_frame":"2 years","description":"Elimination rate constant"},{"outcome_type":"secondary","measure":"t1/2","time_frame":"2 years","description":"Elimination half life time"},{"outcome_type":"secondary","measure":"CL/F","time_frame":"2 years","description":"Clearance"},{"outcome_type":"secondary","measure":"Vd/F","time_frame":"2 years","description":"Apparent volume of distribution"},{"outcome_type":"secondary","measure":"Rac","time_frame":"2 years","description":"Accumulation factor"}]}
{"nct_id":"NCT04923945","start_date":"2021-08-19","phase":"Phase 3","enrollment":163,"brief_title":"Savolitinib for Treating Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Patients","official_title":"A Multi-center, Open-label, Phase IIIb Confirmatory Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of Savolitinib in Treating Locally Advanced or Metastatic NSCLC Patients With MET Exon 14mutations","primary_completion_date":"2024-07-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-09-02","description":"Treating Non-small Cell Lung Cancer (NSCLC) Patients with MET exon 14mutations with Savolitinib","other_id":"2020-504-00CH2","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"locally advanced or metastatic NSCLC patients with MET exon 14 mutations without EGFR, ALK and ROS1 sensitive mutations who had disease progression or intolerable toxicity after previous therapy with platinum-based chemotherapeutic regimen and are treatment-nave to c-MET therapy OR who did not receive any drug therapy for advanced tumors previously.","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Fully aware this study and signed the informed consent form in voluntary manner, and\r\n             willing and able to comply with the study procedure;\r\n\r\n          2. Age 18 years;\r\n\r\n          3. Histologically diagnosed locally advanced or metastatic NSCLC with MET exon 14\r\n             mutation;\r\n\r\n          4. Cohort 1: disease progression or intolerable toxicity after previous therapy with\r\n             platinum-based chemotherapeutic regimen (for the patients who have received\r\n             platinum-based adjuvant chemotherapy/radiotherapy, neoadjuvant\r\n             chemotherapy/radiotherapy previously or radical radiochemotherapy for progressive\r\n             disease, if the disease progression occurred < 6 months after the end of the last\r\n             therapy, the patient belongs to failure after the first-line therapy); Cohort 2: no\r\n             any previous systematic antitumor therapy for advanced diseases;\r\n\r\n          5. Having measurable lesions (in accordance with RECIST 1.1 criteria);\r\n\r\n          6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1, or Karnofsky\r\n             performance status 80;\r\n\r\n          7. Survival is expected to exceed 12 weeks;\r\n\r\n          8. Adequate functionality in bone marrow, liver, kidney\r\n\r\n          9. Able to take or swallow the drug orally.\r\n\r\n         10. Female patients of childbearing potential must agree to use effective contraceptive\r\n             methods from screening period to 30 days after discontinuation of the study drug,The\r\n             male patients whose sexual partners are women of childbearing age must use condom\r\n             during sexual intercourse during the study and within 6 months after discontinuation\r\n             of study drug;\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Having gene mutations sensitive to targeted drugs for EGFR, ALK and ROS1;\r\n\r\n          2. Currently having other malignant tumors, or having other infiltrating malignant tumors\r\n             in the past 5 years. Stage I malignant tumor after radical treatment for at least 3\r\n             years, except those considered by investigators to have small possibility of\r\n             recurrence. Patients with radically treated carcinoma in situ (non-infiltrating) and\r\n             skin cancer other than malignant melanoma can be enrolled;\r\n\r\n          3. Having received antitumor therapy (including chemotherapy, hormone therapy,\r\n             biotherapy, immunotherapy or traditional Chinese medicine for antitumor indication)\r\n             within 3 weeks prior to the start of study treatment, or having received treatment\r\n             with small molecular tyrosine kinase inhibitors (e.g., EGFR-TKI) within 2 weeks prior\r\n             to the start of study treatment;\r\n      ","sponsor":"Hutchison Medipharma Limited","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer Metastatic","interventions":[{"intervention_type":"Drug","name":"Drug: Savolitinib","description":"Patients meeting the study inclusion criteria will receive Savolitinib [Savolitinib 600 mg, po, once per day (QD) continuously in patients with baseline weight 50 kg, and Savolitinib 400 mg, po, QD in patients with baseline weight <50 kg] in 21 day treatment cycle, until disease progression, death, intolerable toxicity or other termination criteria as specified in the protocol, whichever occurs earliest."}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate (ORR) evaluated by the Independent Review Committee (IRC) (RECIST 1.1 criteria)","time_frame":"through study completion, an average of 3 years","description":"To evaluate the efficacy of Savolitinib in the treatment of locally advanced or metastatic NSCLC patients with MET exon 14 mutations"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) (RECIST 1.1 criteria)","time_frame":"From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months","description":"To evaluate the efficacy of Savolitinib in the treatment of locally advanced or metastatic NSCLC patients with MET exon 14 mutations"},{"outcome_type":"secondary","measure":"incidence of various adverse events (AE)","time_frame":"through study completion, an average of 3 years","description":"To evaluate the safety and tolerability of Savolitinib in the treatment of locally advanced or metastatic NSCLC patients with MET exon 14 mutations"}]}
{"nct_id":"NCT04976634","start_date":"2021-08-18","phase":"Phase 2","enrollment":400,"brief_title":"Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)","official_title":"An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Multiple Solid Tumors","primary_completion_date":"2026-07-07","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-07-07","last_update":"2021-09-09","description":"The purpose of this study is to determine the safety and efficacy of belzutifan in combination with pembrolizumab and lenvatinib in multiple solid tumors including hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and biliary tract cancer (BTC). There is no formal hypothesis testing in this study.","other_id":"6482-016","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"This study will initially enroll 120 participants (30 per each of the four tumor types). Following an interim analysis of the safety and efficacy data for these initial 120 participants, an additional 280 participants (70 per tumor type) may be enrolled, dependent on the results of the interim analysis data.","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Diagnosis of one of the following advanced (unresectable and/or metastatic) solid\r\n             tumors, documented by histopathology or cytopathology:\r\n\r\n               -  HCC\r\n\r\n               -  CRC (non-microsatellite instability-high [non-MSI-H]/deficient mismatch repair\r\n                  [dMMR])\r\n\r\n               -  PDAC\r\n\r\n               -  BTC (includes intrahepatic, extrahepatic cholangiocarcinoma [CCA] and gall\r\n                  bladder cancer)\r\n\r\n          -  Disease progression on or since the most recent treatment (does not apply to newly\r\n             diagnosed unresectable or metastatic HCC).\r\n\r\n          -  Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified\r\n             by BICR.\r\n\r\n          -  Submission of an archival tumor tissue sample or newly obtained core or excisional\r\n             biopsy of a tumor lesion not previously irradiated.\r\n\r\n          -  Male participants are abstinent from heterosexual intercourse or agree to follow\r\n             contraceptive guidance during and for at least 7 days after last dose of study\r\n             intervention with belzutifan and lenvatinib.\r\n\r\n          -  Female participants are not pregnant or breastfeeding, not a woman of child-bearing\r\n             potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during\r\n             the intervention period and and for at least 120 days after the last dose of\r\n             pembrolizumab or for at least 30 days after last dose of lenvatinib or belzutifan,\r\n             whichever occurs last.\r\n\r\n          -  Adequate organ function.\r\n\r\n          -  Adequately controlled blood pressure with or without antihypertensive medications.\r\n\r\n          -  HCC Specific Inclusion Criteria: No prior systemic chemotherapy, including anti-VEGF\r\n             therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational\r\n             anticancer agents for advanced/unresectable HCC (1L).\r\n\r\n          -  CRC ([non-MSI-H/dMMR) Specific Inclusion Criteria: Received at least 2 prior lines of\r\n             systemic therapy for unresectable or metastatic disease which includes\r\n             fluoropyrimidine, irinotecan and oxaliplatin.\r\n\r\n          -  PDAC Specific Inclusion Criteria: Prior therapy with at least 1 (platinum or\r\n             gemcitabine containing regimen) but no more than 2 prior systemic therapies for\r\n             unresectable or metastatic pancreatic cancer.\r\n\r\n          -  BTC Specific Inclusion Criteria: Received at least 1 prior line of systemic therapy\r\n             (containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Unable to swallow orally administered medication or presence of a gastrointestinal\r\n             (GI) disorder that may affect study intervention absorption.\r\n\r\n          -  History of a second malignancy that is progressing or has required active treatment\r\n             within 3 years.\r\n\r\n          -  Hypoxia (defined as a pulse oximeter reading <92% at rest), or requirement of\r\n             intermittent supplemental oxygen/ chronic supplemental oxygen.\r\n\r\n          -  Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis.\r\n\r\n          -  Clinically significant cardiovascular disease within 6 months of first dose of study\r\n             intervention.\r\n\r\n          -  Symptomatic pleural effusion, unless clinically stable after treatment.\r\n\r\n          -  Preexisting  Grade 3 GI or non-GI fistula.\r\n\r\n          -  Moderate to severe hepatic impairment.\r\n\r\n          -  Clinically significant history of bleeding within 3 months before screening.\r\n\r\n          -  Presence of serious active nonhealing wound/ulcer/bone fracture.\r\n\r\n          -  Requirement for hemodialysis or peritoneal dialysis.\r\n\r\n          -  History of human immunodeficiency virus (HIV) infection.\r\n\r\n          -  History of Hepatitis B or active Hepatis C virus infections, with exceptions for HCC\r\n             and BTC.\r\n\r\n          -  Prior therapy with an anti-programmed cell-death (PD-1), anti-PD-L1, anti-PD-L2 agent,\r\n             lenvatinib or belzutifan.\r\n\r\n          -  Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major\r\n             blood vessel.\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Carcinoma, Hepatocellular|Colorectal Neoplasms|Pancreatic Ductal Adenocarcinoma|Biliary Tract Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Pembrolizumab 400 mg administered Q6W via IV infusion"},{"intervention_type":"Drug","name":"Drug: Belzutifan","description":"Belzutifan 120 mg administered QD via oral tablet"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvantinib dose for HCC is 8 mg QD for body weight <60 kg and 12 mg QD for body weight  60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)","time_frame":"Up to approximately 21 days","description":"Occurrence of any of the following will be considered a DLT if possibly, probably, or definitely related to study treatment administration: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting >7 days; Grade 4 thrombocytopenia-any duration; Grade 3 thrombocytopenia if associated with clinically significant hemorrhage; Febrile neutropenia Grade 3 or Grade 4; Grade 3 nonhematologic toxicity lasting >5 days despite optimal supportive care; Grade 3 hypertension not controlled by antihypertensive medication(s); Grade 3 or Grade 4 nonhematologic laboratory abnormality (if medical intervention is required, or leads to hospitalization, or persists for >1 week) ; Elevated bilirubin if persists >4 weeks (for HCC and BTC participants only); Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment-related toxicity resulting in participant discontinuation of study intervention during the DLT window; Grade 5 toxicity."},{"outcome_type":"primary","measure":"Number of Participants Who Experience at Least One Adverse Event (AE)","time_frame":"Up to approximately 45 months","description":"An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be presented."},{"outcome_type":"primary","measure":"Number of Participants Who Discontinue Study Treatment Due to an AE","time_frame":"Up to approximately 44 months","description":"An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented separately for the safety lead-in phase (up to 21 days) and the main study."},{"outcome_type":"primary","measure":"Confirmed Objective Response Rate (ORR) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 45 months","description":"ORR is defined as the percentage of participants who have a Complete Response (CR) or a Partial Response (PR) per RECIST 1.1, as assessed by blinded independent central review (BICR)."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. The DOR per RECIST 1.1 will be assessed by BICR."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"DCR is defined as the percentage of participants who have a CR, PR, or Stable Disease (SD). The best overall response of CR, PR, or SD after ≥ 6 weeks will be assessed per RECIST 1.1 by BICR."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"PFS is defined as the time from first day of study intervention to the first documented progressive disease (PD) per RECIST1.1 as assessed by BICR, or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 45 months","description":"OS is defined as the time from the first day of study intervention to death due to any cause."},{"outcome_type":"secondary","measure":"ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"ORR is defined as the percentage of participants who have a CR or a PR per mRECIST 1.1 for HCC, as assessed by BICR."},{"outcome_type":"secondary","measure":"DOR Per mRECIST 1.1 for HCC as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"DOR is defined as the time from the first documented evidence of CR or PR until either progressive disease (PD) or death due to any cause, whichever occurs first. The DOR per mRECISIT 1.1 for HCC willl be assessed by BICR."},{"outcome_type":"secondary","measure":"DCR Per mRECIST 1.1 for HCC as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"DCR is defined as the percentage of participants who have a CR or PR or SD. The best overall response of CR, PR, or SD after ≥ 6 weeks per mRECIST 1.1 for HCC will be assessed by BICR."},{"outcome_type":"secondary","measure":"PFS Per mRECIST 1.1 for HCC as Assessed by BICR","time_frame":"Up to approximately 45 months","description":"PFS is defined as the time from first day of study intervention to the first documented PD per mRECIST 1.1 for HCC as assessed by BICR, or death due to any cause, whichever occurs first."}]}
{"nct_id":"NCT04924192","start_date":"2021-08-18","phase":"Phase 2","enrollment":126,"brief_title":"A Clinical Study of TQB3616 Capsules Combined With Anlotinib Hydrochloride Capsules or Standard Chemotherapy Second-line and Above in the Treatment of Advanced Lung Cancer","official_title":"A Clinical Study of TQB3616 Capsules Combined With Anlotinib Hydrochloride Capsules or Standard Chemotherapy Second-line and Above in the Treatment of Advanced Lung Cancer","primary_completion_date":"2023-05-23","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-30","last_update":"2021-09-21","description":"This is an open, multi-cohort, exploratory phase II study on the safety and efficacy of TQB3616 combined with Anlotinib hydrochloride capsules or standard chemotherapy in the treatment of advanced lung cancer.","other_id":"TQB3616-ALTN-II-01","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Subjects with pathologically proven small cell lung cancer(SCLC) or/and locally\r\n             advanced ( Stage B/ C), metastatic or recurrent (Stage IV) non small cell lung\r\n             cancer(NSCLC).\r\n\r\n          2. Cohort 1: Subjects with SCLC who had previously received at least one chemotherapy\r\n             containing platinum or got disease progression during chemoradiotherapy or after the\r\n             last treatment.\r\n\r\n          3. Cohort 2: Subjects with locally advanced, metastatic/relapsed NSCLC who had previously\r\n             received only one PD (L) 1 inhibitor alone or in combination with platinum-based\r\n             chemotherapy.\r\n\r\n          4. Subjects with measurable lesions as defined by RECIST 1.1.\r\n\r\n          5. Aged  18 years ; Eastern Cooperative Oncology Group (ECOG) score: 0 ~ 1; Expected\r\n             survival  3 months.\r\n\r\n          6. Laboratory indicators meet the requirements.\r\n\r\n          7. Non-pregnant or non-breastfeeding women; Negative pregnancy subjects.\r\n\r\n          8. Subjects voluntarily joined the study and signed the informed consent form.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Subjects who received prior therapy with anlotinib hydrochloride capsules.\r\n\r\n          2. Cohort 2: Subjects with epidermal growth factor receptor(EGFR) mutation and anaplastic\r\n             lymphoma kinase(ALK) translocation.\r\n\r\n          3. Subjects with central squamous cell carcinoma with a risk of hemoptysis.\r\n\r\n          4. Subjects who have developed or is currently suffering from other malignancies within 5\r\n             years, with the exception of cured skin basal cell carcinoma and cervical carcinoma in\r\n             situ.\r\n\r\n          5. Subjects who have brain metastases with symptoms or control of symptoms for less than\r\n             2 months.\r\n\r\n          6. Subjects with difficulty taking oral medication.\r\n\r\n          7. Subjects with uncontrolled pleural effusion, pericardial effusion or ascites requiring\r\n             repeated drainage.\r\n\r\n          8. Subjects with spinal cord compression who have failed to be cured or relieved by\r\n             surgery and or radiotherapy.\r\n\r\n          9. Subjects who have received chemotherapy, radiotherapy or other experimental anticancer\r\n             therapy within 4 weeks prior to the first dose of the drug.\r\n\r\n         10. Subjects who have not recovered to  CTCAE Grade 1 (excluding alopecia) due to the\r\n             adverse event of prior therapy.\r\n\r\n         11. Subjects with significant surgery or significant traumatic injury within 28 days\r\n             before randomization.\r\n\r\n         12. Subjects with arterial/venous thrombosis within 6 months.\r\n\r\n         13. Subjects with a history of psychotropic substance abuse who cannot be withdrawn or\r\n             have mental disorders.\r\n\r\n         14. Subjects with any severe and/or uncontrolled disease.\r\n\r\n         15. Subjects whose large vessels are involved by tumor from imaging (CT or MRI).\r\n\r\n         16. Subjects who have hemoptysis and maximum daily hemoptysis  2.5ml within 1 month\r\n             before the first dose.\r\n\r\n         17. Subjects with other factors that might cause the study to be terminated halfway per\r\n             the judgement of the investigator.\r\n\r\n             -\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Lung Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Irinotecan Hydrochloride for Injection","description":"An inhibitor of DNA topoisomerase "},{"intervention_type":"Drug","name":"Drug: TQB3616 capsules","description":"A CDK4/6 kinase inhibitor"},{"intervention_type":"Drug","name":"Drug: Anlotinib Hydrochloride capsules","description":"A multi-target receptor tyrosine kinase inhibitor"}],"outcomes":[{"outcome_type":"primary","measure":"Overall response rate (ORR)","time_frame":"up to 96 weeks","description":"Percentage of participants achieving complete response (CR) and partial response (PR)."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"up to 96 weeks","description":"PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Disease control rate（DCR）","time_frame":"up to 96 weeks","description":"Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD)."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"up to 120 weeks","description":"The time when the participants first achieved CR or PR to disease progression or death from any cause."},{"outcome_type":"secondary","measure":"6-month progression-free survival rate","time_frame":"up to 96 weeks","description":"PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"6-month and 12-month overall survival rate","time_frame":"up to 96 weeks","description":"OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive."}]}
{"nct_id":"NCT05008783","start_date":"2021-08-16","phase":"Phase 3","enrollment":500,"brief_title":"A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma","official_title":"A Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of AK104 Plus Oxaliplatin and Capecitabine (XELOX) Versus Placebo Plus XELOX as First-line Treatment for Locally Advanced Unresectable or G/GEJ Adenocarcinoma","primary_completion_date":"2024-01-14","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-04-14","last_update":"2021-08-17","description":"A randomized, Double-blind, Multicenter, phase III Clinical Study of Comparing the Efficacy and Safety of AK104 Plus Oxaliplatin and Capecitabine (XELOX) Versus Placebo Plus XELOX as First-line Treatment for locally advanced Unresectable or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma.","other_id":"Ak104-302","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Subjects must meet all of the following inclusion criteria to be enrolled in the\r\n             study:\r\n\r\n               1. Ability to understand and voluntarily sign a written informed consent form (ICF),\r\n                  which must be signed before the specified study procedures required for the study\r\n                  are performed.\r\n\r\n               2. Males or females aged  18 to  75 years at the time of signing informed consent.\r\n\r\n               3. Histopathologically confirmed gastric adenocarcinoma or gastroesophageal junction\r\n                  (GEJ) adenocarcinoma.\r\n\r\n               4. Unresectable locally advanced or metastatic gastric adenocarcinoma or GEJ\r\n                  adenocarcinoma.\r\n\r\n               5. Subjects have not received prior systemic therapy for locally advanced or\r\n                  metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal\r\n                  junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy\r\n                  or chemoradiotherapy for curative intent, the time between disease progression\r\n                  and last treatment should be at least 6 months.\r\n\r\n               6. Subjects have at least one measurable tumor lesion per RECIST v1.1; lesions that\r\n                  received radiotherapy are not selected as target lesions, unless the lesion is\r\n                  the only measurable lesion and has unequivocal progression as judged by imaging,\r\n                  it can be considered as a target lesion.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects who meet any of the following criteria are not eligible to participate in\r\n             this study:\r\n\r\n               1. Subjects with known HER2-positive gastric or GEJ adenocarcinoma.\r\n\r\n               2. Histopathology or cytology confirmed other pathological types, such as squamous\r\n                  cell carcinoma, sarcoma, or undifferentiated carcinoma.\r\n\r\n               3. Subjects who received palliative local therapy for non-target lesions within 2\r\n                  weeks prior to the first dose; systemic nonspecific immunomodulatory therapy\r\n                  (e.g., interleukin, interferon, thymosin, etc.) within 2 weeks prior to the first\r\n                  dose; and Chinese herbal medicine or traditional Chinese medicinal products with\r\n                  anti-tumor indications within 2 weeks prior to the first dose.\r\n\r\n               4. Subjects who received any prior treatments targeting the mechanism of tumor\r\n                  immunity.\r\n\r\n               5. Medical history of gastrointestinal perforation or gastrointestinal fistula\r\n                  within 6 months prior to the first dose. If the perforation or fistula has been\r\n                  treated with resection or repair and the disease has recovered or resolved as\r\n                  judged by the Investigator, enrollment may be allowed.\r\n\r\n               6. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease\r\n                  or ulcerative colitis).\r\n\r\n               7. Active malignancies within the past 3 years, with the exception of tumors in this\r\n                  study and cured local tumors, such as basal cell carcinoma of skin, squamous cell\r\n                  carcinoma of skin, superficial bladder cancer, carcinoma in situ of cervix,\r\n                  carcinoma in situ of breast, localized prostate cancer, etc.\r\n\r\n               8. Known active or untreated brain metastases, meningeal metastases, spinal cord\r\n                  compression, or leptomeningeal disease.\r\n\r\n               9. Presence of clinically symptomatic pleural effusion, pericardial effusion, or\r\n                  ascites requiring frequent drainage ( 1/month).\r\n\r\n              10. Active autoimmune disease requiring systemic treatment within 2 years prior to\r\n                  the start of study treatment, or autoimmune diseases that may relapse or require\r\n                  scheduled treatment as judged by the Investigator.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"Gastric Adenocarcinoma|Gastroesophageal Junction Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: AK104","description":"AK104 (administered on Day 1 of each cycle, Q3W)+Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Capecitabine(1000 mg/m2, p.o., Bid, Q3W,up to 6 cycles) . Afterward, AK104 will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W)"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Placebo (administered on Day 1 of each cycle, Q3W)+Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Capecitabine(1000 mg/m2, p.o., Bid, Q3W,up to 6 cycles) . Afterward,Placebo will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W)"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"Up to 2 years","description":"PFS assessed by BIRC per RECIST v1.1 in the ITT population."},{"outcome_type":"primary","measure":"Overall Survival (os)","time_frame":"Up to 2 years","description":"OS in the ITT population."},{"outcome_type":"secondary","measure":"ORR","time_frame":"Up to 2 years","description":"ORR is the proportion of subjects with CR or PR based on RECIST v1.1"},{"outcome_type":"secondary","measure":"DCR","time_frame":"Up to 2 years","description":"DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1"},{"outcome_type":"secondary","measure":"DoR","time_frame":"Up to 2 years","description":"DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"TTR","time_frame":"Up to 2 years","description":"TTR is defined as the time to response base on RECIST v1.1"},{"outcome_type":"secondary","measure":"PFS","time_frame":"Up to 2 years","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1"},{"outcome_type":"secondary","measure":"AE","time_frame":"From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first","description":"Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results."},{"outcome_type":"secondary","measure":"Observed concentrations of AK104","time_frame":"From first dose of AK104 through the last dose of AK104, about average of 9 months.","description":"The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration"},{"outcome_type":"secondary","measure":"Number of subjects who develop detectable anti-drug antibodies (ADAs)","time_frame":"From first dose of AK104 through 30 days after last dose of AK104","description":"The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs)."}]}
{"nct_id":"NCT05001724","start_date":"2021-08-13","phase":"Phase 2/Phase 3","enrollment":522,"brief_title":"KN046 Plus Lenvatinib in Subject With Advanced Non-Small Cell Lung Cancer in the Failure of Anti-PD-(L)1 Agent","official_title":"A Randomized, Open-Label, Active-Controlled, Multi-Center Study to Compare Efficacy, Safety, and Tolerability of KN046 Combined With Lenvatinib Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer After Failure of Anti-PD-(L)1 Agent","primary_completion_date":"2024-06-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-09-30","last_update":"2021-08-12","description":"This is a phase 2/3, multicenter, randomized, open, positive-controlled study of patients with advanced non-small cell lung cancer whose disease has progressed after prior anti-PD-(L)1 therapy. Subjects should have documented progressive disease during prior treatment with first- or second-line PD-(L)1 and platinum-containing dual-agent chemotherapy.Subjects will be randomized to three treatment groups in a 4:1:4 ratio. Treatment Group 1: KN046 5mg/kg every 2 weeks + lenvatinib recommended for phase III dose (RP3D) every day. Treatment Group 2: lenvatinib RP3D every day . Control group: Docetaxel 75mg/m2 every 3 weeks .","other_id":"KN046-302","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":80,"population":"","criteria":"\n        Inclusion criteria:\r\n\r\n          -  Has a histologically confirmed or cytologically confirmed diagnosis of advanced NSCLC;\r\n\r\n          -  No known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma\r\n             kinase (ALK) reshoots;\r\n\r\n          -  Has received prior systemic treatment with first- or second-line PD-(L)1 and\r\n             platinum-containing dual-agent chemotherapy for their advanced NSCLC;\r\n\r\n          -  Has measurable disease;\r\n\r\n          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)\r\n             Performance Status;\r\n\r\n          -  Has adequate organ function;\r\n\r\n          -  Has a life expectancy of at least 3 months;\r\n\r\n          -  If female of childbearing potential, have a negative serum pregnancy test within 7\r\n             days prior to first trial treatment;\r\n\r\n          -  If female of childbearing potential or a male subject with a partner with childbearing\r\n             potential, be willing to use a highly effective method of contraception (with a\r\n             failure rate of less than 1.0% per year) from first study treatment to 24 weeks after\r\n             completion of the trial treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Untreated active central nervous system metastasis or leptomeningeal metastasis;\r\n\r\n          -  Is currently participating and receiving an investigational drug or has participated\r\n             in a study of an investigational drug within 4 weeks or within 5 times of half-life\r\n             (no less than 2 weeks), whichever is shorter prior to the first dose of trial\r\n             treatment;\r\n\r\n          -  Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the first\r\n             administration of trial treatment and/or if the subject has not fully recovered from\r\n             the surgery within 4 weeks of the first administration of trial treatment;\r\n\r\n          -  Curative radiation within 3 months of the first dose of trial treatment;\r\n\r\n          -  Subjects receiving immunosuppressive agents (such as steroids) for any reason should\r\n             be tapered off these drugs before initiation of trial treatment (with the exception of\r\n             subjects with adrenal insufficiency, who may continue corticosteroids at physiologic\r\n             replacement doses, equivalent to < 10 mg prednisone daily, inhaled steroids and\r\n             topical use of steroids);\r\n\r\n          -  Vaccination within 28 days of the first administration of trial treatment, except for\r\n             administration of inactivated vaccines;\r\n\r\n          -  Has interstitial lung disease, or a history of pneumonitis that required oral or\r\n             intravenous glucocorticoids to assist with management;\r\n\r\n          -  History or current active autoimmune disease that might deteriorate when receiving an\r\n             immunostimulatory agent;\r\n\r\n          -  Previous malignant disease;\r\n\r\n          -  History of uncontrolled intercurrent illness;\r\n\r\n          -  Prior therapy with any antibody/drug targeting T cell coregulatory proteins;\r\n\r\n          -  Has received treatment with lenvatinib or docetaxel or VEGFR-TKI;\r\n\r\n          -  Known severe hypersensitivity reactions to antibody drug;\r\n\r\n          -  Is pregnant or breastfeeding;\r\n\r\n          -  Other medical conditions that at the discretion of investigator interfere with the\r\n             requirements of the trial in terms of safety or efficacy evaluation, or treatment\r\n             compliance.\r\n      ","sponsor":"Jiangsu Alphamab Biopharmaceuticals Co., Ltd","sponsor_type":"Industry","conditions":"Advanced Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: KN046","description":"KN046 is 5 milligram per kilogram, every 2 weeks."},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib is RP3D milligram per day, every day."},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Docetaxel is 75 milligram per Square meter, every 3 weeks."}],"outcomes":[{"outcome_type":"primary","measure":"DLT","time_frame":"28 days","description":"Dose limit toxicity (phase 2)"},{"outcome_type":"primary","measure":"OS","time_frame":"up to 2 years","description":"Overall survival (OS) was defined as the time from randomization to death due to any cause (phase 3)."},{"outcome_type":"primary","measure":"PFS","time_frame":"up to 2 years","description":"Progression-free survival (PFS) was defined as the time from randomization grouping to the first documented disease progression or death from any cause as evaluated by the investigator according to RECIST 1.1 criteria (phase 3)."},{"outcome_type":"secondary","measure":"ORR","time_frame":"up to 2 years","description":"Objective response rate (ORR) based on the RECIST 1.1 by principal investigator"},{"outcome_type":"secondary","measure":"DCR","time_frame":"up to 2 years","description":"Disease control rate (DCR) based on the RECIST 1.1 by principal investigator"},{"outcome_type":"secondary","measure":"DOR","time_frame":"up to 2 years","description":"Duration of response (DOR) based on the RECIST 1.1 by principal investigator"},{"outcome_type":"secondary","measure":"CBR","time_frame":"up to 2 years","description":"Clinical benefit rate (CBR) based on the RECIST 1.1 by independent review committee"},{"outcome_type":"secondary","measure":"TTR","time_frame":"up to 2 years","description":"Time to response (TTR) based on the RECIST 1.1 by independent review committee"},{"outcome_type":"other","measure":"Safety endpoint","time_frame":"up to 2 years","description":"Serious adverse events (SAE), changes and abnormal findings in laboratory test, vital sign and physical examination."}]}
{"nct_id":"NCT04974398","start_date":"2021-08-13","phase":"Phase 3","enrollment":278,"brief_title":"A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma","official_title":"A Randomized, Double-blind, Multi-center Phase III Study of Penpulimab (AK105) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-10-31","last_update":"2021-08-30","description":"This study is a randomized, double-blind, multi-center phase III clinical study to compare the efficacy and safety of penpulimab combined with chemotherapy and placebo combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma.","other_id":"AK105-304","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Voluntarily signed written Informed Consent Form(ICF).\r\n\r\n          -  Age of  18 years and  75 years at the time of enrollment, male or female.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Expected survival of  3 months.\r\n\r\n          -  Histologically or cytologically confirmed nasopharyngeal carcinoma.\r\n\r\n          -  Subjects with primary metastatic (nasopharyngeal carcinoma, stage IVB defined by the\r\n             Union for International Cancer Control and the American Joint Committee on Cancer\r\n             Staging System edition 8) nasopharyngeal carcinoma who are not suitable for local\r\n             treatment or radical treatment; or nasopharyngeal carcinoma subjects who have a\r\n             local-regional recurrence and/or distant metastasis more than 6 months after the end\r\n             of previous radical treatment (radiotherapy with induction, concurrent, adjuvant\r\n             chemotherapy)No systemic treatment has been received for recurrent or metastatic\r\n             nasopharyngeal carcinoma, and local regional recurrence is not suitable for local\r\n             treatment or has received local treatment.\r\n\r\n          -  At least one measurable lesion according to RECIST v1.1;\r\n\r\n          -  Has adequate organ function.\r\n\r\n          -  All female and male subjects of reproductive potential must agree to use an effective\r\n             method of contraception, as determined by the Investigator, during and for 150 days\r\n             after the last dose of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects with pathologically diagnosed nasopharyngeal adenocarcinoma or sarcoma.\r\n\r\n          -  Subjects have had another malignancy within 3 years before the first dose, except\r\n             nasopharyngeal carcinoma. Subjects with other malignancies that have been cured by\r\n             local therapy such as basal or cutaneous squamous cell carcinoma, superficial bladder\r\n             cancer, cervix or breast carcinoma in situ are not excluded.\r\n\r\n          -  Participation in treatment with an investigational drug or use of an investigational\r\n             device within 4 weeks before first study dosing.\r\n\r\n          -  Have previously received immunotherapy, including immune checkpoint inhibitors, immune\r\n             checkpoint agonists , immune cell therapy, and other treatments against tumor immune\r\n             mechanism.\r\n\r\n          -  Active autoimmune disease requiring systemic treatment within 2 years prior to initial\r\n             administration, or as an autoimmune disease that can recur or for which treatment is\r\n             planned determined by the investigator.\r\n\r\n          -  Active or past history of definite inflammatory bowel disease (e.g., Crohn's disease\r\n             or ulcerative colitis).\r\n\r\n          -  History of immunodeficiency; those who test positive for HIV antibody; current chronic\r\n             use of systemic corticosteroids or immunosuppressive agents.\r\n\r\n          -  Known active tuberculosis (TB) (suspected of having active TB need to undergo clinical\r\n             examination for exclusion of such possibility); known active syphilis infection.\r\n\r\n          -  Known history of allotransplantation and allogeneic hematopoietic stem cell\r\n             transplantation.\r\n\r\n          -  Has known active Hepatitis B or Hepatitis C.\r\n\r\n          -  Active or untreated CNS metastases.\r\n\r\n          -  Subjects with peripheral neuropathy.\r\n\r\n          -  Unresolved toxicity from prior anti-tumor therapy, defined as toxicity that has not\r\n             recovered .\r\n\r\n          -  Received a live vaccine within 30 days before the first dose or planned to receive a\r\n             live vaccine during the study.\r\n\r\n          -  Known allergy to any study drug component; known history of serious hypersensitivity\r\n             to other monoclonal antibodies.\r\n\r\n          -  Pregnant or nursing (lactating) women.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"Nasopharyngeal Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Penpulimab","description":"Group A: Penpulimab (200 mg, administered on Day 1 of each cycle, Q3W) + cisplatin (80 mg/m2, administered on Day 1 of each cycle, Q3W, up to 6 cycles) + gemcitabine (1000 mg/ m2, administered on Days 1 and 8 of each cycle, Q3W, up to 6 cycles), 3 weeks (21 days) per treatment cycle. Afterward, penpulimab will be used for maintenance treatment (200 mg, administered on Day 1 of each cycle, Q3W)."},{"intervention_type":"Drug","name":"Drug: placebo","description":"Group B: Placebo (200 mg, administered on Day 1 of each cycle, Q3W) + cisplatin (80 mg/m2, administered on Day 1 of each cycle, Q3W, up to 6 cycles) + gemcitabine (1000 mg/m2, on Days 1 and 8 of each cycle, Q3W, up to 6 cycles), every 3 weeks (21 days) per treatment cycle. Afterward, a placebo will be used for maintenance treatment (200 mg, administered on Day 1 of each cycle, Q3W)."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"Up to 2 years","description":"PFS assessed by BIRC based on RECIST v1.1 ."},{"outcome_type":"secondary","measure":"Overall survival(OS)","time_frame":"Up to 4 years","description":"OS is defined as the time from the date of randomization to death from any cause."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"Up to 2 years","description":"ORR is the proportion of subjects with CR or PR based on RECIST v1.1."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Up to 2 years","description":"DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Up to 2 years","description":"DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1;"},{"outcome_type":"secondary","measure":"Adverse event (AE)","time_frame":"From the time of informed consent signed through 90 days after the last dose of penpulimab","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment"},{"outcome_type":"secondary","measure":"Maximum observed concentration (Cmax)","time_frame":"From first dose of penpulimab through 30 days after last dose of penpulimab","description":"Serum concentrations of penpulimab in individual subjects at different time points after penpulimab administration."},{"outcome_type":"secondary","measure":"Anti-drug antibodies (ADA)","time_frame":"From first dose of penpulimab through 30 days after last dose of penpulimab","description":"Number and percentage of subjects with detectable anti-drug antibody (ADA)."},{"outcome_type":"secondary","measure":"PD-L1 expression","time_frame":"Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration).","description":"Detect PD-L1 expression in tumor samples and evaluate the correlation between PD-L1 and efficacy."},{"outcome_type":"secondary","measure":"Blood EBV level","time_frame":"Up to 2 years","description":"Detect the blood EBV level at baseline and changes after administration and evaluate the correlation between EBV and efficacy"}]}
{"nct_id":"NCT04964479","start_date":"2021-08-06","phase":"Phase 3","enrollment":375,"brief_title":"A Clinical Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsules Versus K Drug in the Treatment of First-line Non-small Cell Lung Cancer(NSCLC)","official_title":"A Randomized, Blind, Parallel Controlled, Multicenter Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsules Versus Pembrolizumab Injection as a First-line Treatment on Patient With Advanced NSCLC.","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-03-31","last_update":"2021-08-20","description":"A clinical study to evaluate the efficacy and safety of TQB2450 injection combined with Anlotinib Hydrochloride capsules versus K drug as a first-line treatment of advanced non-small cell lung cancer.A total of 375 subjects will be enrolled.","other_id":"TQB2450-III-09","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Single","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  According to the 8th edition of the International Association for the Study of Lung\r\n             Cancer and the American Joint Committee on Cancer Classification, the tumor node\r\n             metastasis (TNM) staging of lung cancer is locally advanced (stage B/C), metastatic\r\n             or recurrent ( Stage IV) NSCLC patients. (Note: Mixed tumors will be classified\r\n             according to the main cell type; if there are small cell components, the subject is\r\n             unqualified).\r\n\r\n          -  Between the ages of 18-75 years (calculated based on the date of signing ICF); male or\r\n             female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time \r\n             3 months.\r\n\r\n          -  According to the RECIST 1.1 standard, there is at least one measurable lesion. If the\r\n             measurable lesion is located in the radiotherapy area, it should be clearly defined as\r\n             a progressive state.\r\n\r\n          -  Patients who have not received systemic anti-tumor therapy for advanced, recurrent or\r\n             metastatic diseases in the past. For those who have received adjuvant chemotherapy in\r\n             the past, the interval between the recurrence time and the last adjuvant chemotherapy\r\n             should be at least 6 months; The interval between the end of previous radiotherapy for\r\n             chest and this treatment should be more than 6 months, and the interval between\r\n             palliative radiotherapy for chest and this treatment should be more than 7 days.\r\n\r\n          -  Tumor tissue slices that have not undergone radiotherapy at or after the diagnosis of\r\n             advanced or metastatic NSCLC must be provided. Tumor tissue samples must be archived\r\n             samples or fresh samples obtained within 12 months before randomization, and the\r\n             proportion of programmed death-Ligand 1(PD-L1) positive tumor cells 1% (TPS  1%).\r\n\r\n          -  For non-squamous NSCLC, patients with no epidermal growth factor receptor (EGFR)\r\n             mutations and ALK fusions (for squamous NSCLC, patients with known EGFR mutations and\r\n             anaplastic Lymphoma kinase (ALK) fusions need to be excluded, and those with unknown\r\n             status are not mandatory to be tested).\r\n\r\n          -  The function of main organs are well and meet the following standards:\r\n\r\n             a. Routine blood examination standards (without blood transfusion or correction with\r\n             hematopoietic stimulating factor drugs within 14 days before screening): i. Absolute\r\n             neutrophil count (ANC) 1.5109 /L; ii. Platelets 100109 /L; iii. Hemoglobin 90\r\n             g/L. b. The blood biochemical examination shall meet the following standards: i. Total\r\n             bilirubin (TBIL)  2  upper limit of normal (ULN) (Patients with Gilbert syndrome  3\r\n              ULN); ii. Alanine aminotransferase (ALT) and aspartate aminotransferase\r\n             (AST)2.5ULN. If it is accompanied by liver metastasis, ALT and AST5ULN; iii. Serum\r\n             creatinine (Cr) 1.5ULN or creatinine clearance estimated by Cockcroft-Gault\r\n             glomerular filtration formula 60 mL/min; iv. Serum albumin (ALB) 30g/L. c. Urine\r\n             routine examination standard: urine routine indicates urine protein <++; if urine\r\n             protein ++, it is necessary to confirm that the 24-hour urine protein quantitative\r\n             1.0 g.\r\n\r\n             d. Blood coagulation test standards: prothrombin time (PT), activated partial\r\n             thromboplastin time (APTT), international normalized ratio (INR)1.5ULN (no\r\n             anticoagulant therapy).\r\n\r\n             e. Thyroid Stimulating Hormone (TSH)  ULN; if abnormal, T3 and T4 levels should be\r\n             examined. If T3 and T4 levels are normal, it can be selected.\r\n\r\n             f. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction\r\n             (LVEF) 50%.\r\n\r\n             g. 12-lead ECG evaluation: QTc<450ms (male), QTc<470ms (female).\r\n\r\n          -  Women of childbearing age should agree to use effective contraceptive measures during\r\n             the study period and 6 months after the end of the study, and have a negative serum\r\n             pregnancy test within 7 days before the study enrollment; men should agree to the\r\n             study period and 6 months after the end of the study period Effective contraceptive\r\n             measures must be used internally.\r\n\r\n          -  The subjects voluntarily joined the study, signed the informed consent form, and had\r\n             good compliance.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Tumor disease and medical history:\r\n\r\n               1. Brain metastases without local treatment; Note: Subjects who have previously\r\n                  received brain metastasis therapy and meet all the following criteria can\r\n                  participate in this study: i. Only supratentorial and cerebellar metastases; ii.\r\n                  The condition needs to be stable for 4 weeks and no new brain metastases or\r\n                  brain metastases are found Expanded imaging evidence; iii. The subject must have\r\n                  stopped corticosteroids/dehydrator for at least 2 weeks before starting to use\r\n                  the trial drug;\r\n\r\n               2. There are midbrain, pons, medulla oblongata, spinal cord and meningeal\r\n                  metastases\r\n\r\n               3. Other malignant tumors appeared or were present within 3 years. The following two\r\n                  cases can be included: other malignant tumors treated by single operation have\r\n                  achieved 5-year Disease-free survival (DFS) in a row; The cured cervical\r\n                  carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta\r\n                  (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement\r\n                  membrane)];\r\n\r\n               4. Central type, cavity squamous cell carcinoma (primarily in the main bronchus and\r\n                  around the hilar);\r\n\r\n               5. Imaging shows that the tumor invades large blood vessels or is unclearly\r\n                  separated from the blood vessels, or the investigator judges that the tumor is\r\n                  likely to invade important blood vessels and cause fatal bleeding during the\r\n                  subsequent study(The major vessels in the chest include pulmonary aorta, left\r\n                  pulmonary artery, right pulmonary artery, four pulmonary veins, superior vena\r\n                  cava, inferior vena cava and aorta);\r\n\r\n               6. Severe bone injury caused by tumor bone metastasis, including pathological\r\n                  fracture of weight-bearing bone and spinal cord compression that occurred within\r\n                  6 months or is expected to occur in the near future(Such as spine, pelvis, femur,\r\n                  tibia, phalanges, calcaneus, etc.);\r\n\r\n               7. Patients with serous cavity (thoracic cavity, abdominal cavity, or pericardial\r\n                  cavity) that require repeated drainage to relieve clinical symptoms (as\r\n                  determined by the investigator), or who have received drainage of serous cavity\r\n                  effusion for the purpose of treatment within 2 weeks before treatment.\r\n\r\n          -  Previous anti-tumor treatments:\r\n\r\n               1. Received the treatment of proprietary Chinese medicines with anti-tumor\r\n                  indications specified in the NMPA approved drug instructions within 2 weeks\r\n                  before the start of the study treatment(Including compound cantharidin capsules,\r\n                  Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica\r\n                  oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.);\r\n\r\n               2. Previously received related immunotherapy drugs for programmed death 1 (PD-1),\r\n                  PD-L1, cytolytic T lymphocyte-associated antigen-4 (CTLA-4), etc.;\r\n\r\n               3. Previous use of anti-angiogenic drugs such as bevacizumab, anlotinib, apatinib,\r\n                  lenvatinib, sorafenib, sunitinib, regorafenib, fruquintinib, etc.;\r\n\r\n               4. Patients who have been vaccinated with immunomodulatory drugs within 30 days\r\n                  before starting treatment(Such as interleukin-2, thymosin, lentinan, etc.);\r\n\r\n               5. Failure to recover from the toxicity and/or complications of previous\r\n                  interventions to CTCAE 1, except for hair loss and peripheral neuropathy 2;\r\n\r\n          -  Combined diseases and medical history:\r\n\r\n             a. Liver cirrhosis, active hepatitis*;(Note: active hepatitis (hepatitis B reference:\r\n             HBV-DNA > 1*103 copy /mL or > 2000IU/mL) when HBsAg is positive. Hepatitis C\r\n             reference: HCV antibody is positive, and HCV titer detection value exceeds the upper\r\n             limit of normal value); b. Renal abnormalities: i.Renal failure requires hemodialysis\r\n             or peritoneal dialysis; ii.Previous or existing nephrotic syndrome, chronic nephritis.\r\n             c. Cardiovascular and cerebrovascular abnormalities i.Patients with previous or\r\n             present heart failure, degree II or above heart block: ii.Myocardial infarction or\r\n             unstable angina, supraventricular or ventricular arrhythmia with clinical significance\r\n             need treatment or intervention; iii.Vascular embolism and cerebrovascular accident\r\n             (including transient ischemic attack, cerebral hemorrhage and cerebral infarction)\r\n             occurred within 9 months Prophylactic use of anticoagulant therapy is allowed for\r\n             patients with thrombotic tendency or undergoing anticoagulant therapy.) iv.After more\r\n             than two kinds of drug treatment, blood pressure control is still not ideal (systolic\r\n             blood pressure  150 mmHg or diastolic blood pressure  90 mmHg).\r\n\r\n             d. Gastrointestinal abnormalities: i.Inability to take medications (such as inability\r\n             to swallow, intestinal obstruction, etc.); ii.A history of malabsorption syndrome or\r\n             other diseases that interfere with gastrointestinal absorption; iii.Received treatment\r\n             for active peptic ulcer in the past 6 months; iv.Despite the maximum medical\r\n             treatment, chronic diarrhea of grade 2 and above continues to occur; v.Other\r\n             conditions determined by the researcher that may cause gastrointestinal bleeding and\r\n             perforation.\r\n\r\n             e. History of immunodeficiency: i.Have a history of immunodeficiency, including HIV\r\n             positive or other acquired or congenital immunodeficiency diseases; ii.Active\r\n             autoimmune disease or history of autoimmune disease, including but not limited to\r\n             Crohn's disease, ulcerative colitis, autoimmune\r\n             hepatitis/enteritis/vasculitis/nephritis, etc.\r\n\r\n        iii.Prepare to undergo or have previously received an organ transplant; iv.Patients who\r\n        require systemic or topical immunosuppressive therapy to achieve immunosuppressive purposes\r\n        and need to continue to use them within two weeks before randomization (except for\r\n        glucocorticoid daily dose <10 mg prednisone or other equivalent hormones).\r\n\r\n        Note: Hormone replacement therapy (such as thyroxine, insulin, or physiological\r\n        corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not\r\n        considered as systemic therapy and allowed to be used.\r\n\r\n        f. Bleeding risk: i.Suffered from bleeding or coagulopathy within 28 days before the start\r\n        of treatment or was using warfarin, aspirin and other antiplatelet agglutination drugs\r\n        (except for aspirin 100 mg/d preventive drugs); ii.Had hemoptysis >2.5 mL/day in 28 days\r\n        before the start of treatment; iii.Regardless of the severity, patients with any history of\r\n        bleeding or coagulopathy; iv.Received major surgical treatment, open biopsy, etc. within 28\r\n        days before the start of the study treatment; v.Long-term unhealed wounds or fractures,\r\n        except for pathological fractures; g. Poor control of type I diabetes or II diabetes\r\n        (fasting blood glucose (FBG)> 10mmol/L); h. Severe infections within 4 weeks before the\r\n        start of study treatment, including but not limited to hospitalization due to bacteremia,\r\n        severe pneumonia, or other severe infections; subjects with  grade 2 active infections\r\n        within 4 weeks before the start of study treatment Or fever of unknown cause occurred\r\n        during the screening period and before the first administration>38.0; i. Past or existing\r\n        pneumoconiosis, interstitial pneumonia, (non-infectious) pneumonia that requires adrenal\r\n        corticosteroid therapy, currently suffering from other types of pneumonia 2, or lung\r\n        function tests confirmed severely impaired lung function (Forced Expiratory Volume in the\r\n        first second (FEV1) or diffusing capacity of lung for carbon monoxide(DLCO) or DLCO per\r\n        alveolar volume (DLCO /VA) accounts for the expected value %<40%) and other objective\r\n        evidence; j. Patients with active tuberculosis within 1 year before enrollment; subjects\r\n        with a history of active pulmonary tuberculosis infection 1 year ago must provide clear\r\n        evidence of cure before enrollment; if tuberculosis is suspected during the screening\r\n        period, chest radiographs and sputum must be passed Enter the group only after the liquid\r\n        and clinical symptoms are eliminated; k. Allergies, or a history of severe allergies in the\r\n        past, or severe hypersensitivity reactions after receiving other monoclonal antibody\r\n        treatments, or known allergies to the ingredients of the study drug excipients; l. Previous\r\n        history of severe mental disorders; m. People with a history of drug abuse, alcohol or drug\r\n        abuse;\r\n\r\n          -  The end of the previous clinical study (last dose) is less than 4 weeks or the study\r\n             drug's 5 half-lives, whichever is shorter.\r\n\r\n          -  Live attenuated vaccine vaccination history within 28 days before randomization or\r\n             planned live attenuated vaccination during the study period. Seasonal influenza\r\n             vaccine for injection is usually an inactivated virus vaccine and is allowed to be\r\n             vaccinated during the study period.\r\n\r\n          -  Female patients during pregnancy or lactation.\r\n\r\n          -  According to the investigator's point of view, it may increase the risks associated\r\n             with participating in the study, or other severe, acute or chronic medical diseases or\r\n             laboratory abnormalities that may interfere with the interpretation of the study\r\n             results, or other reasons that are not suitable for participating in this clinical\r\n             study.\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TQB2450 injection","description":"1200mg injection once every 3 week"},{"intervention_type":"Drug","name":"Drug: Anlotinib Hydrochloride Capsules","description":"12mg capsule once daily"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab injection","description":"200mg injection once every 3 week"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Placebo capsule once daily"}],"outcomes":[{"outcome_type":"secondary","measure":"OS rate of 12 months","time_frame":"Baseline to up to two years","description":"The proportion of subjects who survive for 12 months after the first dose"},{"outcome_type":"primary","measure":"Disease progression-free survival(PFS) evaluated by Independent Review Committee (IRC)","time_frame":"Baseline to up to two years","description":"The period from the first use of the drug to disease progression or death (whichever occurs first)"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Baseline to up to two years","description":"The preriod from the first use of the drug to death from all causes. For subjects who are still alive at the last follow-up, the OS will be counted as data censored based on the last follow-up. For subjects who are lost follow-up, the OS will be counted as data censored based on the last confirmed survival time before being lost to follow-up."},{"outcome_type":"secondary","measure":"Disease PFS evaluated by investigators","time_frame":"Baseline to up to two years","description":"The period from the first use of the drug to disease progression or death (whichever occurs first)"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) evaluated by investigators","time_frame":"Baseline to up to two years","description":"According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST, the proportion of subjects whose tumors are evaluated as complete response(CR) and partial response(PR) by subcenter imaging evaluation. It is recorded from the first use of the drug to disease progression or initiation of a new anticancer treatment."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Baseline to up to two years","description":"Proportion of subjects whose tumors shrink or remain stable for a certain period, including CR, PR and stable disease（SD）"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"Baseline to up to two years","description":"The period from firstly-recorded objective tumor response (CR or PR) to firstly-recorded objective tumor progression or death due to any cause (whichever occurs first) ."},{"outcome_type":"secondary","measure":"DOR rate (≥ 6 months) (the proportion of subjects with DOR ≥ 6 months)","time_frame":"Baseline to up to two years","description":"The proportion of subjects reaching 6 months from firstly- recorded objective tumor response (CR or PR) to firstly-recorded objective tumor progression or death due to any cause (whichever occurred first) ."},{"outcome_type":"secondary","measure":"Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)，as well as abnormal laboratory examination indicators.","time_frame":"Baseline to up to two years","description":"The proportion of AEs and SAEs recorded afte signing the informed consent form(ICF)."}]}
{"nct_id":"NCT04774380","start_date":"2021-08-05","phase":"Phase 3","enrollment":150,"brief_title":"Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer","official_title":"A Phase IIIb, Single-arm, Multi-center, International Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer (LUMINANCE)","primary_completion_date":"2023-03-07","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-12-08","last_update":"2021-07-21","description":"Study to determine the safety and tolerability profile of durvalumab with platinum (cisplatin or carboplatin) plus etoposide (EP) as first-line treatment in participants with extensive-stage small-cell lung cancer.","other_id":"D419QC00007","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically- or cytologically-documented ES-SCLC (stage IV [T any, N any, M1 a/b],\r\n             or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal\r\n             volume that is too large to be encompassed in a tolerable radiation plan (Brain\r\n             metastases; must be asymptomatic or treated and stable off steroids and\r\n             anticonvulsants for at least 1 month prior to study treatment)\r\n\r\n          -  Participants must be considered suitable to receive a platinum-based chemotherapy\r\n             regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either\r\n             cisplatin or carboplatin in combination with etoposide\r\n\r\n          -  World Health Organization/ Eastern Cooperative Oncology Group performance status of 0\r\n             to 2 at enrollment Baseline computed tomography/ magnetic resonance imaging results of\r\n             the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior\r\n             to the treatment initiation\r\n\r\n          -  No prior exposure to immune-mediated therapy including, but not limited to, other\r\n             anti- CTLA-4, anti-Programmed cell death-1 (PD-1), anti- Programmed cell death\r\n             ligand-1 (PD-L1), and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic\r\n             anticancer vaccines\r\n\r\n          -  Adequate organ and marrow function\r\n\r\n          -  Body weight > 30 kg\r\n\r\n          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for\r\n             female pre-menopausal participants\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of allogeneic organ transplantation\r\n\r\n          -  Active or prior documented autoimmune or inflammatory disorders, systemic lupus\r\n             erythematosus, sarcoidosis syndrome, or wegener syndrome\r\n\r\n          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active\r\n             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable\r\n             angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease,\r\n             serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric\r\n             illness/social situations that would limit compliance with study requirement,\r\n             substantially increase risk of incurring AEs or compromise the ability of the\r\n             participant to give written informed consent\r\n\r\n          -  History of another primary malignancy except for:\r\n\r\n               -  Malignancy treated with curative intent and with no known active disease  5\r\n                  years before the first dose of Investigational medicinal product (IMP) and of low\r\n                  potential risk for recurrence\r\n\r\n               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence\r\n                  of disease\r\n\r\n               -  Adequately treated carcinoma in situ without evidence of disease\r\n\r\n          -  History of leptomeningeal carcinomatosis and active primary immunodeficiency\r\n\r\n          -  Active infection including tuberculosis, hepatitis B, hepatitis C, human\r\n             immunodeficiency virus\r\n\r\n          -  Any unresolved toxicity Common Terminology Criteria for Adverse Events Grade  2 from\r\n             previous anticancer therapy\r\n\r\n          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug\r\n             excipients\r\n\r\n          -  Received prior systemic therapy for ES-SCLC\r\n\r\n          -  Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based\r\n             chemotherapy\r\n\r\n          -  Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment.\r\n             Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable\r\n\r\n          -  Planned consolidation chest radiation therapy. Radiation therapy outside of the chest\r\n             for palliative care is allowed but must be completed before first dose of the study\r\n             medication\r\n\r\n          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of in IMP\r\n\r\n          -  Major surgical procedure within 28 days prior to the first dose of IMP\r\n\r\n          -  Participants who have received prior anti-PD-1 or anti PD-L1\r\n\r\n          -  Current or prior use of immunosuppressive medication within 14 days before the first\r\n             dose of durvalumab\r\n\r\n          -  Participation in another clinical study with an investigational product administered\r\n             in the last 4 weeks\r\n\r\n          -  Female participants who are pregnant or breastfeeding or male or female participants\r\n             of reproductive potential who are not willing to employ effective birth control from\r\n             screening to 90 days after the last dose of durvalumab\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Extensive-stage Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"Participants will receive durvalumab via IV infusion on Day 1 of each cycle."},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Participants will receive cisplatin via IV administration on Day 1 of each cycle."},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Participants will receive carboplatin via IV administration Day 1 of each cycle.."},{"intervention_type":"Drug","name":"Drug: Etoposide","description":"Participants will receive etoposide via IV administration on days 1 to 3 of each cycle."}],"outcomes":[{"outcome_type":"secondary","measure":"Percentage of participants remaining in response, 12 months from the time of first documented objective response (DoR12)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating DoR12 according to RECIST 1.1."},{"outcome_type":"primary","measure":"Number of participants with incidence of Grade 3 and higher adverse events (AEs)","time_frame":"Until disease progression (Approximately upto 2 Years)","description":"Assessment of incidence of Grade 3 and higher adverse events to evaluate safety and tolerability profile of durvalumab + EP treatment."},{"outcome_type":"primary","measure":"Number of participants with incidence of Immune mediated adverse events (imAEs)","time_frame":"Until disease progression (Approximately upto 2 Years)","description":"Assessment of imAEs to evaluate safety and tolerability profile of durvalumab + EP treatment."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of efficacy of durvalumab + EP treatment by evaluating PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The PFS is the time from the first date of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from Investigational medicinal product (IMP) or receives another anticancer therapy prior to progression."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating ORR according to RECIST 1.1. The ORR will be assessed based on Investigator-assessed response to treatment of complete response (CR) and partial response (PR), per RECIST1.1."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating DoR according to RECIST 1.1. The DoR is time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression."},{"outcome_type":"secondary","measure":"Percentage of participants alive and progression-free at 12 months from first date of treatment (PFS12)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating PFS12 according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Overall (OS)","time_frame":"From screening until death due to any cause (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating OS according to RECIST 1.1. The OS is the time from the first date of treatment until death due to any cause."},{"outcome_type":"secondary","measure":"Percentage of participants alive at 12 months from first date of treatment (OS12)","time_frame":"From screening until disease progression (Approximately 2 Years)","description":"Assessment of the efficacy of durvalumab + EP treatment by evaluating OS12 according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Number of participants with adverse events and serious adverse events","time_frame":"From Cycle 1 (3 weeks [21 days]) until disease progression (Approximately 2 Years)","description":"Assessment of adverse events and serious adverse events to evaluate safety and tolerability profile of durvalumab + EP treatment."},{"outcome_type":"secondary","measure":"Number of participants with adverse events of special interests","time_frame":"From Cycle 1 (3 weeks [21 days]) until disease progression (Approximately 2 Years)","description":"Assessment of adverse events of special interests to evaluate safety and tolerability profile of durvalumab + EP treatment."}]}
{"nct_id":"NCT04960709","start_date":"2021-08-05","phase":"Phase 3","enrollment":830,"brief_title":"Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin","official_title":"A Phase III Randomized, Open-Label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab in Combination With Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer","primary_completion_date":"2025-07-10","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2028-08-31","last_update":"2021-09-22","description":"A Global Study to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer","other_id":"D910PC00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Parallel","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically documented muscle-invasive TCC of the bladder with\r\n             clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology;\r\n\r\n          -  Medically fit for cystectomy and able to receive neoadjuvant therapy;\r\n\r\n          -  Patients who have not received prior systemic chemotherapy or immunotherapy for\r\n             treatment of MIBC;\r\n\r\n          -  ECOG performance status of 0,1,2 at enrollment.\r\n\r\n          -  Availability of tumor sample prior to study entry;\r\n\r\n          -  Must have a life expectancy of at least 12 weeks at randomization.\r\n\r\n        Exclusion criteria:\r\n\r\n          -  Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.\r\n\r\n          -  Active infection\r\n\r\n          -  Uncontrolled intercurrent illness\r\n\r\n          -  Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin\r\n             [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or\r\n             anti-PD-L2 antibodies.\r\n\r\n          -  Current or prior use of immunosuppressive medication within 14 days before the first\r\n             dose of IPs.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Muscle Invasive Bladder Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"Anti- PD-L1 Antibody"},{"intervention_type":"Drug","name":"Drug: Tremelimumab","description":"Human IgG2 mAb"},{"intervention_type":"Drug","name":"Drug: Enfortumab Vedotin","description":"Nectin-4-directed antibody and microtubule inhibitor conjugate"},{"intervention_type":"Procedure","name":"Procedure: Radical Cystectomy","description":"For cisplatin-ineligible patients"}],"outcomes":[{"outcome_type":"primary","measure":"Safety and Tolerability as evaluated by adverse events occurring throughout the study","time_frame":"At completion of study treatment by the last patient and at 3 months.","description":"Frequency of Adverse Events."},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (blood pressure in mmHg)","time_frame":"Up to 84 months"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed ssessed by vital signs (pulse rate) in beats per minute","time_frame":"Up to 84 months"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (respiration rate) in breaths per minute","time_frame":"Up to 84 months"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (temperature) in degrees Celsius","time_frame":"Up to 84 months"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by liver function","time_frame":"Up to 84 months","description":"Clinical chemistry will be assessed by liver function assessment (ALT, AST, albumin, total bilirubin measured in units per dL)"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by kidney function","time_frame":"Up to 84 months","description":"Clinical chemistry will be assessed by kidney function assessment in mg/dL"},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by thyroid function","time_frame":"Up to 84 months","description":"Clinical chemistry will be assessed by thyroid function assessment in units per mL."},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology","time_frame":"Up to 84 months","description":"Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count."},{"outcome_type":"primary","measure":"Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by ECG (pulse rate)","time_frame":"Up to 84 months"},{"outcome_type":"primary","measure":"Changes in WHO/ECOG performance status","time_frame":"Up to 84 months","description":"Eastern Cooperative Oncology Group (ECOG) performance status scale range 0 to 5, where 0 is fully active, able to carry on all pre disease performance without restriction - best outcome and 5 -death - worst outcome."},{"outcome_type":"primary","measure":"Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on pCR rate","time_frame":"Up to 3 years","description":"Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per central pathological review using specimens obtained via cystectomy, up to 3 years."},{"outcome_type":"primary","measure":"Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on EFS","time_frame":"Up to 3 years","description":"Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years."},{"outcome_type":"secondary","measure":"1.Pathologic complete response (pCR) rates at time of cystectomy in Arm 2 vs Arm 3","time_frame":"3 years","description":"Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per central pathological review using specimens obtained via cystectomy, at 3 years."},{"outcome_type":"secondary","measure":"2.Event-free survival (EFS) defined as time from randomization to event in Arm 2 vs Arm 3","time_frame":"Up to 5 years","description":"Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 5 years."},{"outcome_type":"secondary","measure":"3.Overall survival","time_frame":"Up to 5 years","description":"Overall Survival is defined as length of time from randomization until the date of death due to any cause, whichever came first, assessed up to 5 years."},{"outcome_type":"secondary","measure":"4.EFS at 24 months (EFS24)","time_frame":"Up to 24 months","description":"EFS24 is defined as proportion of participants alive and event-free at 24 months"},{"outcome_type":"secondary","measure":"5.Overall survival rate at 5 years","time_frame":"At 5 years","description":"The proportion of participants alive at 5 years (OS5) is defined as the Kaplan-Meier estimate of OS at 5 years after randomization"},{"outcome_type":"secondary","measure":"6.Disease-free survival (DFS)","time_frame":"Up to first recurrence of disease or death up to 5 years","description":"DFS is defined as time from radical cystectomy to recurrence or death, whichever came first, assessed up to 5 years."},{"outcome_type":"secondary","measure":"7.Pathologic downstaging (pDS) rate-to < pT2","time_frame":"3 years","description":"pDS rate is defined as the rate of downstaging to < pT2, including pT0, pTis, pTa, pT1, and N0"},{"outcome_type":"secondary","measure":"8.Disease-specific survival (DSS)","time_frame":"from randomization until death due to bladder cancer up to 5 year.","description":"DSS is defined as time from randomization until death due to bladder cancer, assessed up to 5 years."},{"outcome_type":"secondary","measure":"9.EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire)","time_frame":"from baseline and time to definitive clinically, assessed up to 5 years"},{"outcome_type":"secondary","measure":"10.Immunogenicity of durvalumab when used in combination with Tremelimumab as measured by presence of antidrug antibodies (ADA)","time_frame":"At 3 months after last dose of durvalumab and tremelimumab"},{"outcome_type":"secondary","measure":"11.Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab and tremelimumab","time_frame":"At 3 months after last dose of durvalumab and tremelimumab"},{"outcome_type":"secondary","measure":"11.Time to maximum observed serum concentration (tmax) of durvalumab and tremelimumab","time_frame":"At 3 months after last dose of durvalumab and tremelimumab"}]}
{"nct_id":"NCT04973163","start_date":"2021-08-03","phase":"Phase 1","enrollment":245,"brief_title":"A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation","official_title":"A Phase Ia/Ib, Open-label, Multicentre Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of BI 1823911 as a Monotherapy and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumours Expressing KRAS G12C Mutation","primary_completion_date":"2024-10-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-10-01","last_update":"2021-09-16","description":"This study is open to adults with different types of advanced or metastatic cancer (including lung cancer, colorectal cancer, pancreatic cancer, and bile duct cancer). This study is for people for whom previous treatment was not successful or no treatment exists. People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes tumours grow faster. BI 1823911 and BI 1701963 are medicines that may turn off KRAS, each in a different way. In this study, BI 1823911 is given to people for the first time. The purpose of this study is to find the highest dose of BI 1823911 that people can tolerate when taken alone and together with BI 1701963. The most suitable dose is used to find out whether BI 1823911 alone and in combination with BI 1701963 can make tumours shrink. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, participants take tablets of BI 1823911 alone or in combination with BI 1701963 once a day. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participant's health.","other_id":"1472-0001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"The following parts will be included in this trial:\r\nFirst: Monotherapy Arm\r\nAfter confirmation of safety: Combination Therapy Arm\r\nEach arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C)).","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Pathologically confirmed diagnosis of locally advanced or metastatic solid tumours,\r\n             e.g. adenocarcinoma of the lung, colorectal cancer, pancreatic cancer or\r\n             cholangiocarcinoma. Non-small cell lung cancer (NSCLC) patients with mixed histology\r\n             are eligible if adenocarcinoma is the predominant histology.\r\n\r\n          -  Documented disease progression despite appropriate prior standard therapies or for\r\n             whom no standard therapy exists for their tumour type and disease stage.\r\n\r\n          -  KRAS mutation status: Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine\r\n             (G12C) mutation in tumour tissue or blood based on previously performed local testing\r\n             using a validated test.\r\n\r\n          -  Provision of archival tumour tissue, if available, to confirm retrospectively KRAS\r\n             G12C mutation status and for biomarker assessment.\r\n\r\n          -  Only parts B and C monotherapy and combination therapy: Willingness to undergo pre-\r\n             and on-treatment tumour biopsies for pharmacodynamics and biomarker assessment.\r\n\r\n        Patients can be enrolled without tumour biopsy upon agreement between the Investigator and\r\n        the Sponsor if tumour biopsy is not feasible.\r\n\r\n        In addition, pre- and on-treatment biopsies are optional for part A monotherapy and\r\n        combination therapy.\r\n\r\n          -  At least one target lesion that can be measured per Response Evaluation Criteria In\r\n             Solid Tumours (RECIST) version 1.1 (radiated lesions do not qualify as target\r\n             lesions). In patients who only have one target lesion, and a biopsy of the lesion is\r\n             required, the baseline imaging must be performed before the biopsy or at the earliest\r\n             two weeks after the biopsy.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Adequate organ function as follows:\r\n\r\n               -  Absolute neutrophil count (ANC) 1.5 x 109/L (equivalent values:  1.5 x 103/L\r\n                  or  1500/mm3); hemoglobin 9.0 g/dL (equivalent values:  90 g/L or  5.6\r\n                  mmol/L); platelets 100 x 109/L (equivalent values:  100 x 103/L or  100 x\r\n                  103/mm3) without the use of haematopoietic growth factors.\r\n\r\n               -  Total bilirubin 1.5 times the upper limit of normal (ULN), or 4 x ULN for\r\n                  patients who are known to have Gilbert's syndrome.\r\n\r\n               -  Creatinine 1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if\r\n                  concurrent creatinine clearance 50 mL/min (equivalent value: 0.84 mL/s)\r\n                  (measured or calculated by The Chronic Kidney Disease Epidemiology Collaboration\r\n                  (CKD-EPI) formula).\r\n\r\n               -  Aspartate transaminase (AST) and alanine transaminase (ALT) 3 x ULN, for\r\n                  patients with liver metastases 5 x ULN.\r\n\r\n        Further inclusion criteria apply.\r\n\r\n        Exclusion Criteria:\r\n\r\n        - Previous anticancer chemotherapy within 3 weeks of the first administration of trial\r\n        drug.\r\n\r\n        Previous anticancer hormonal treatment or anticancer immunotherapy within 2 weeks of the\r\n        first administration of trial drug.\r\n\r\n          -  Previous treatment with Rat Sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or\r\n             Son of sevenless 1 (SOS1) targeting agents (only for monotherapy Parts A, B, and C).\r\n\r\n          -  Radiotherapy within 2 weeks prior to start of treatment, provided recovery from\r\n             related toxicity.\r\n\r\n          -  Major surgery (major according to the investigator's assessment) performed within 4\r\n             weeks prior to start of treatment or planned during the projected course of the trial,\r\n             e.g.\r\n\r\n        hip replacement.\r\n\r\n          -  Previous treatment with any investigational agent(s) or targeted treatment within 28\r\n             days prior to start of treatment or 5 half-lives, whichever is shorter.\r\n\r\n          -  Known history of hypersensitivity to any of the excipients of BI 1823911 tablets.\r\n\r\n          -  History or presence of cardiovascular abnormalities such as uncontrolled hypertension,\r\n             congestive heart failure New York Heart Association (NYHA) classification of 3,\r\n             unstable angina or poorly controlled arrhythmia which are considered clinically\r\n             relevant by the Investigator. Myocardial infarction within 6 months prior to start of\r\n             treatment. Uncontrolled hypertension is defined as: Blood pressure (BP) measured in a\r\n             rested and relaxed condition, where systolic BP >=140 mmHg, or diastolic BP >= 90\r\n             mmHg, with or without medication.\r\n\r\n          -  Left ventricular ejection fraction (LVEF) <50%. Further exclusion criteria apply.\r\n      ","sponsor":"Boehringer Ingelheim","sponsor_type":"Industry","conditions":"Solid Tumors, KRAS Mutation","interventions":[{"intervention_type":"Drug","name":"Drug: BI 1823911","description":"BI 1823911"},{"intervention_type":"Drug","name":"Drug: BI 1701963","description":"BI 1701963"},{"intervention_type":"Drug","name":"Drug: Midazolam","description":"Midazolam - only administered in Part B (dose confirmation) of the Monotherapy Arm"}],"outcomes":[{"outcome_type":"secondary","measure":"All study parts, BI 1823911: Steady state concentration (Css)","time_frame":"up to 24 hours"},{"outcome_type":"primary","measure":"Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for BI 1823911 in monotherapy and in each combination","time_frame":"up to 28 days","description":"DLTs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0."},{"outcome_type":"primary","measure":"Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR) defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR)","time_frame":"up to 39 months","description":"BOR is determined according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.\r\nBOR will consider all tumour assessments from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent."},{"outcome_type":"secondary","measure":"Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing DLTs during all treatment cycles for BI 1823911 in monotherapy and in each combination","time_frame":"up to 39 months"},{"outcome_type":"secondary","measure":"Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR)","time_frame":"up to 39 months","description":"OR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), both regardless of confirmation.\r\nBOR is determined according to RECIST version 1.1. BOR will consider all tumour assessments from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent."},{"outcome_type":"secondary","measure":"Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Duration of OR","time_frame":"up to 39 months","description":"Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR."},{"outcome_type":"secondary","measure":"Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Tumour shrinkage (in millimetres)","time_frame":"up to 39 months","description":"Tumour shrinkage is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions."},{"outcome_type":"secondary","measure":"Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Progression-free survival (PFS) rate","time_frame":"at month 6","description":"PFS is defined as the time from first treatment administration until tumour progression according to RECIST version 1.1 or death from any cause, whichever occurs earlier."},{"outcome_type":"secondary","measure":"All study parts: Number of patients with adverse events during the on-treatment period","time_frame":"up to 39 months"},{"outcome_type":"secondary","measure":"All study parts, BI 1823911: Maximum concentration (Cmax)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1823911: Area under the plasma concentration-time curve from time zero to time t (AUCτ)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1823911: Area under the plasma concentration-time curve at steady state (AUCss)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1701963: Maximum concentration (Cmax)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1701963: Steady state concentration (Css)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1701963: Area under the plasma concentration-time curve from time zero to time t (AUCτ)","time_frame":"up to 24 hours"},{"outcome_type":"secondary","measure":"All study parts, BI 1701963: Area under the plasma concentration-time curve at steady state (AUCss)","time_frame":"up to 24 hours"}]}
{"nct_id":"NCT04943627","start_date":"2021-08-02","phase":"Phase 3","enrollment":486,"brief_title":"Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA)","official_title":"A Phase 3 Trial of Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer After Platinum-Based Chemotherapy (BRAVA)","primary_completion_date":"2026-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-11-30","last_update":"2021-08-04","description":"This Phase 3 trial is an open-label, randomized study with single-agent Balstilimab (BAL) or Investigator Choice (IC) chemotherapy (single-agent gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan) in patients with recurrent, persistent, or metastatic cervical cancer who have progressed after receiving platinum based chemotherapy.","other_id":"C-700-03","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Voluntarily agree to participate by giving written informed consent.\r\n\r\n          2.  18 years of age.\r\n\r\n          3. Diagnosis and prior systemic treatment:\r\n\r\n               1. Has recurrent or metastatic cervical cancer (SCC, AC, or ASC histology) and has\r\n                  experienced disease progression during or after treatment with a standard\r\n                  platinum based therapy with or without bevacizumab.\r\n\r\n               2. Has received at least 1 prior systemic therapy regimen for recurrent, persistent,\r\n                  and/or metastatic cervical cancer.\r\n\r\n             Note: Chemotherapy administered in the adjuvant or neoadjuvant setting, or in\r\n             combination with radiation therapy, should not be counted as a prior systemic therapy\r\n             regimen for recurrent, persistent, and/or metastatic cervical cancer.\r\n\r\n          4. Measurable disease - based on Investigator assessment.\r\n\r\n             a. Radiological evidence of measurable disease on imaging based on RECIST v1.1 Note:\r\n             Patients must have at least 1 \"target lesion\" to be used to assess response, as\r\n             defined by RECIST v1.1. Tumors within a previously irradiated field will be designated\r\n             as \"non target\" lesions unless progression is documented, or a biopsy is obtained to\r\n             confirm persistence at least 90 days following completion of radiation therapy.\r\n\r\n          5. Has a life expectancy of at least 3 months and an ECOG performance status of 0 or 1.\r\n\r\n          6. Patients must have sufficient and adequate formalin-fixed tumor tissue sample\r\n             available that is not older than 3 years; otherwise, a fresh biopsy is required.\r\n             Archival tissue or fresh biopsy must be from a site not previously irradiated.\r\n\r\n          7. Has adequate organ function as indicated by the following laboratory values:\r\n\r\n               1. Adequate hematological function defined by absolute neutrophil count  1.5 \r\n                  109/L, platelet count  100  109/L, and stable hemoglobin  8 g/dL (without\r\n                  transfusions within 1 week before first dose).\r\n\r\n               2. Adequate hepatic function based by a total bilirubin level  1.5  the upper\r\n                  limit of normal (ULN), aspartate aminotransferase (AST) level  2.5  ULN,\r\n                  alanine aminotransferase (ALT) level  2.5  ULN, alkaline phosphatase (ALP) \r\n                  2.5  ULN, and albumin  3.0 mg/dL. In the case of hepatic metastases, < 5  ULN\r\n                  for AST/ALT and ALP.\r\n\r\n               3. Adequate renal function defined as calculated creatinine clearance > 40 mL/min or\r\n                  a serum creatinine < 1.5  ULN, per institutional standards (creatinine clearance\r\n                  should be calculated per institutional standards).\r\n\r\n               4. Adequate coagulation defined by international normalized ratio or prothrombin\r\n                  time  1.5  institutional upper limit of normal IULN unless the patient is\r\n                  receiving anticoagulant therapy) and activated partial thromboplastin time  1.5\r\n                   IULN (unless the patient is receiving anticoagulant therapy).\r\n\r\n               5. Normal thyroid function (thyroid stimulating hormone) whether or not the patient\r\n                  is on supplemental thyroid hormone.\r\n\r\n          8. Has no history of another primary malignancy except:\r\n\r\n               1. Malignancy treated with curative intent and with no known active disease  5\r\n                  years before the first dose of study drug and of low potential risk for\r\n                  recurrence.\r\n\r\n               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence\r\n                  of disease.\r\n\r\n               3. Adequately treated carcinoma in situ without evidence of disease.\r\n\r\n          9. Women of childbearing potential (WOCP) must have a negative serum pregnancy test at\r\n             Screening (within 72 hours before first dose of study drug). Non-childbearing\r\n             potential is defined as (by other than medical reasons):\r\n\r\n               1.  45 years of age and has not menstruated for greater than 1 year.\r\n\r\n               2. Definitive pelvic radiation for the treatment of cervical cancer.\r\n\r\n               3. Whose status is post hysterectomy, bilateral oophorectomy, or tubal ligation.\r\n\r\n               4. WOCP must be willing to use 2 highly effective methods of contraception (defined\r\n                  in the informed consent form) throughout the trial, starting with the Screening\r\n                  Visit through 90 days after the last dose of study drug Note: Abstinence is\r\n                  acceptable if this is the established and preferred contraception for the\r\n                  patient.\r\n\r\n         10. Is willing and able to comply with the requirements of the protocol.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Is currently participating and receiving study therapy or has participated in a trial\r\n             of an investigational agent and received study therapy or used an investigational\r\n             device within 4 weeks before the first dose of treatment.\r\n\r\n          2. Has an inadequate period of time prior to first dose of study treatment that is\r\n             defined as:\r\n\r\n               1. Received systemic cytotoxic chemotherapy or biological therapy within 28 days\r\n                  before initiation of study treatment\r\n\r\n               2. Received radiation therapy within 28 days before initiation of study treatment,\r\n                  except for palliative bone therapy, which can be received 2 weeks prior to\r\n                  initiation of study treatment\r\n\r\n               3. Had major surgery within 4 weeks before initiation of study treatment\r\n\r\n          3. Has received prior therapy with:\r\n\r\n             a. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such\r\n             as anti-programmed cell death protein 1 and anti-PD-L1 antibodies.\r\n\r\n          4. Has persisting toxicity related to prior therapy of NCI-CTCAE v5.0 Grade  1 severity,\r\n             with the exceptions noted below:\r\n\r\n               1. Peripheral neuropathy Grade  2.\r\n\r\n               2. Alopecia Grade  2.\r\n\r\n          5. Is expected to require any other form of systemic or localized antineoplastic therapy\r\n             while on trial (including maintenance therapy with another agent, radiation therapy,\r\n             and/or surgical resection).\r\n\r\n          6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI\r\n             CTCAE v5.0 Grade  3), any history of anaphylaxis, or uncontrolled asthma.\r\n\r\n          7. Is receiving systemic corticosteroids  7 days prior to the first dose of trial\r\n             treatment or receiving any other form of systemic immunosuppressive medication\r\n             (corticosteroid use on trial for management of immune-related adverse events and/or as\r\n             a premedication for intravenous [IV] contrast allergies/reactions is allowed).\r\n             Patients who are receiving daily corticosteroid replacement therapy are an exception\r\n             to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5\r\n             mg or equivalent hydrocortisone dose and steroid therapy administered by topical,\r\n             intraocular, intranasal, and/or inhalation routes.\r\n\r\n          8. History of central nervous system tumor, metastasis(es), and/or carcinomatous\r\n             meningitis identified either on the baseline brain imaging obtained during the\r\n             Screening period or identified prior to consent.\r\n\r\n             Note: Patients with a history of brain metastases that have been treated may\r\n             participate provided they show evidence of stable supra-tentorial lesions at screening\r\n             (based on 2 sets of brain images, performed  4 weeks apart, and obtained after the\r\n             brain metastases treatment). In addition, any neurologic symptoms that developed\r\n             either as a result of the brain metastases or their treatment must have resolved or be\r\n             minimal and be expected as sequelae from treated lesions. For individuals who received\r\n             steroids as part of brain metastases treatment, steroids must be discontinued  7 days\r\n             prior to the first dose of study drug.\r\n\r\n          9. Has active or history of autoimmune disease that requires systemic treatment within 2\r\n             years of the start of study drug (ie, with use of disease-modifying agents,\r\n             corticosteroids, or immunosuppressive drugs) Note: Patients with autoimmune conditions\r\n             requiring hormone replacement therapy or topical treatments are eligible.\r\n\r\n         10. Has had an allogeneic tissue/solid organ transplant requiring ongoing\r\n             immunosuppressive treatment.\r\n\r\n         11. Has or had known drug-induced interstitial lung disease, not fully resolved, or has\r\n             had a history of pneumonitis that has required oral or IV corticosteroids.\r\n\r\n         12. Has an active infection requiring IV systemic treatment.\r\n\r\n         13. Has known history of HIV (HIV 1/2 antibodies).\r\n\r\n         14. Has known untreated hepatitis B/hepatitis C virus (HBV/HCV) or tuberculosis. Active\r\n             HBV is defined as a known positive hepatitis B surface antigen result. Active HCV is\r\n             defined as a known positive hepatitis C antibody result and known quantitative HCV RNA\r\n             results greater than the lower limits of detection of the assay.\r\n\r\n         15. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular\r\n             accident/stroke or myocardial infarction within 6 months before enrollment, unstable\r\n             angina, congestive heart failure (New York Heart Association Class  II), or serious\r\n             uncontrolled cardiac arrhythmia requiring medication.\r\n\r\n         16. Has other systemic conditions or organ abnormalities that in the opinion of the\r\n             Investigator may interfere with the conduct and/or interpretation of the current\r\n             trial.\r\n\r\n         17. Has known psychiatric or substance use disorders that would interfere with cooperation\r\n             or compromise participation with the requirements of the trial.\r\n\r\n         18. Is legally incapacitated or has limited legal capacity.\r\n\r\n         19. Is pregnant or breastfeeding.\r\n\r\n         20. Has received a live/attenuated vaccine within 14 days of first dose of study treatment\r\n             and other vaccines within 48 hours of first dose of study treatment.\r\n      ","sponsor":"Agenus Inc.","sponsor_type":"Industry","conditions":"Advanced Cancer|Metastatic Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Balstilimab (BAL)","description":"Anti-PD-1 Monoclonal antibody"},{"intervention_type":"Drug","name":"Drug: Topotecan","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Vinorelbine","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Irinotecan","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Chemotherapy"}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Hazard Ratio for Overall Survival (OS) by treatment assignement, stratified by histology, region of the world, ECOG PS in all patients with PD-L1 positive tumors"},{"outcome_type":"primary","measure":"Overall survival in all patients randomized to BAL vs Investigator's Choice chemotherapy","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Hazard Ratio for OS by treatment assignement, stratified by histology, region of the world, ECOG PS in all patients"},{"outcome_type":"secondary","measure":"Progression-free survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Hazard Ratio for PFS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients with PD-L1 positive tumors"},{"outcome_type":"secondary","measure":"Progression-free survival in all patients randomized to BAL vs Investigator's Choice chemotherapy","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Hazard Ratio for PFS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) to BAL and to IC chemotherapy in patients with PD-L1 positive tumors","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients with PD-L1 positive tumors randomized to BAL and to IC chemotherapy."},{"outcome_type":"secondary","measure":"Objective response rate (ORR) to BAL and to IC chemotherapy in all patients tumors","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients randomized to BAL and to IC chemotherapy."},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Incidence of grade 3+ TEAEs"},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Median duration of grade 3+ TEAE"},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Incidence of serious AEs"},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Incidence of treatment-related TEAEs leading to death"},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Incidence of treatment-related TEAEs leading to treatment discontinuation"},{"outcome_type":"other","measure":"Frequency, severity, and duration of treatment-emergent adverse events (TEAEs) and laboratory abnormalities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"time until observing 234 OS events but no later than 36 months after enrollment of the last patient","description":"Median duration of treatment-related grade 3+ AEs"},{"outcome_type":"other","measure":"To evaluate the PK of BAL - maximum concentration","time_frame":"At the beginning of each Cycle (each cycle is 21 days) through End-of-treatment (EOT) visit (up to 2 years)","description":"Maximum BAL concentration"},{"outcome_type":"other","measure":"To evaluate the PK of BAL - area under the drug concentration-time curve","time_frame":"At the beginning of each Cycle (each cycle is 21 days) through End-of-treatment (EOT) visit (up to 2 years)","description":"Area under BAL concentration-time curve, per dosing cycle"},{"outcome_type":"other","measure":"To evaluate the immunogenicity of BAL and to assess potential impact on study drug exposure and biological activity","time_frame":"At the beginning of each Cycle (each cycle is 21 days) through 90-Day Safety Follow-up visit (3 months after last dose of BAL)","description":"Anti drug antibodies- incidence of anti-balstilimab antibodies including neutralizing antibodies."}]}
{"nct_id":"NCT04987203","start_date":"2021-08-01","phase":"Phase 3","enrollment":326,"brief_title":"Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma","official_title":"TiNivo-2: A Phase 3, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor","primary_completion_date":"2024-07-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-07-01","last_update":"2021-08-03","description":"This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).","other_id":"AV-951-20-304","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Radiographic disease progression during or following at least 6 weeks of treatment\r\n             with ICI for locally advanced or metastatic RCC with a clear cell component either in\r\n             first- or second-line treatment.\r\n\r\n          -  Subjects must have recovered from the adverse events of prior therapy or returned to\r\n             baseline.\r\n\r\n          -  Histologically or cytologically confirmed RCC with a clear cell component.\r\n\r\n          -  Measurable disease per RECIST criteria Version 1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  More than 2 prior lines of therapy in the advanced or metastatic setting.\r\n\r\n          -  History of life-threatening toxicity related to prior immune therapy.\r\n\r\n          -  Active, known, or suspected autoimmune disease.\r\n\r\n          -  Uncontrolled hypertension.\r\n\r\n          -  More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic\r\n             setting.\r\n      ","sponsor":"AVEO Pharmaceuticals, Inc.","sponsor_type":"Industry","conditions":"Renal Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Tivozanib","description":"Tivozanib will be administered orally."},{"intervention_type":"Drug","name":"Drug: Nivolumab","description":"Nivolumab will be administered via intravenous infusion."}],"outcomes":[{"outcome_type":"secondary","measure":"Duration of Response","time_frame":"From Screening (Days -28 to -1) until PD or death (Approximately 30 months)","description":"Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause."},{"outcome_type":"secondary","measure":"Number of subjects with serious and non-serious adverse events","time_frame":"From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)","description":"Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib."},{"outcome_type":"primary","measure":"Progression free survival","time_frame":"until progressive disease [PD] (Approximately 30 months)","description":"Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to Response Evaluation Criteria In Solid Tumors (RECIST), or death due to any reasons whichever comes first."},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"From Screening (Days -28 to -1) until death (Approximately 42 months)","description":"Comparsion of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate","time_frame":"From Screening (Days -28 to -1) until PD (Approximately 30 months)","description":"Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects."}]}
{"nct_id":"NCT04923906","start_date":"2021-08-01","phase":"Phase 3","enrollment":624,"brief_title":"Aumolertinib With or Without Chemotherapy as 1st Line Treatment in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Sensitizing EGFR Mutations","official_title":"Efficacy and Safety of Aumolertinib With or Without Chemotherapy as First-line Treatment in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Sensitizing Epidermal Growth Factor Receptor Mutations: A Randomized, Controlled, Open-label, Phase 3 and Multicenter Clinical Study","primary_completion_date":"2024-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2026-01-31","last_update":"2021-06-11","description":"To assess the efficacy and safety of Aumolertinib plus chemotherapy versus Aumolertinib alone as first-line treatment in locally advanced or metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor mutations (EGFRm+).","other_id":"HS-10296-306","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Provision of informed consent before any study-specific procedures, sampling and\r\n             analyses.\r\n\r\n             2. Male or female, age at least 18 years. 3. Histologically confirmed locally advanced\r\n             or metastatic NSCLC (included patients with stage IIIB, IIIC or IV disease who had\r\n             relapsed after prior surgery or were newly diagnosed). Patients must be\r\n             treatment-nave for locally advanced or metastatic NSCLC. Prior adjuvant and\r\n             neo-adjuvant therapies are permitted as long as treatment was completed at least 12\r\n             months prior to the development of recurrent disease.\r\n\r\n             4. The tumor harbors 1 of the 2 common EGFR mutations known to be associated with\r\n             EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR\r\n             mutations assessed by central testing using tumor tissue sample or blood sample.\r\n\r\n             5. At least 1 lesion that has not previously been irradiated, and that can be\r\n             accurately measured at Baseline as  10 mm in the longest diameter (except lymph\r\n             nodes, which must have short axis  15mm).\r\n\r\n             6. An Eastern Cooperative Oncology Group (ECOG) performance status equal to 0-1 with\r\n             no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.\r\n\r\n             7. Female patients should be using adequate contraceptive measures and should not be\r\n             breastfeeding at the screening period, during the study, and six months after the last\r\n             dosing of study. Patient must have a negative pregnancy test prior to start of dosing\r\n             if of childbearing potential or must have evidence of non-childbearing potential by\r\n             fulfilling 1 of the following criteria at screening:\r\n\r\n               1. Postmenopausal defined as age more than 50 years and amenorrhea for at least 12\r\n                  months following cessation of all exogenous hormonal treatments.\r\n\r\n               2. Women under 50 years old would be considered postmenopausal if they have been\r\n                  amenorrhea for 12 months or more, following cessation of exogenous hormonal\r\n                  treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone\r\n                  (FSH) levels in the postmenopausal range for the laboratory.\r\n\r\n               3. Documentation of irreversible surgical sterilization by hysterectomy, bilateral\r\n                  oophorectomy, or bilateral salpingectomy, but not by tubal ligation.\r\n\r\n                  8. Male patients should be willing to use barrier contraception (i.e., condoms).\r\n\r\n                  Exclusion Criteria:\r\n\r\n          -  1. Treatment with any of the following:\r\n\r\n               1. Prior treatment with an EGFR TKI.\r\n\r\n               2. Major surgery (excluding placement of vascular access) within 4 weeks of\r\n                  randomization.\r\n\r\n               3. Radiotherapy to more than 30% of the bone marrow or with a wide field of\r\n                  radiation within 4 weeks of randomization.\r\n\r\n               4. Spinal cord compression or brain metastases unless asymptomatic, stable for at\r\n                  least 4 weeks, and not requiring steroids for at least 2 weeks prior to start of\r\n                  study treatment.\r\n\r\n               5. Medications that are predominantly CYP3A4 strong inhibitors or inducers or\r\n                  sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of\r\n                  the first dose of study drug.\r\n\r\n                  2. Any unresolved toxicities from prior therapy greater than Common Terminology\r\n                  Criteria for Adverse Events (CTCAE) Grade 2 at the time of starting study\r\n                  treatment.\r\n\r\n                  3. History of other malignancies, excluding full treated non-melanoma skin\r\n                  cancer, in-situ cancer, or other solid tumors that hadn't recurrent for > 5 years\r\n                  following the end of treatment.\r\n\r\n                  4. Inadequate bone marrow reserve or organ function. 5. Any of the following\r\n                  cardiac criteria:\r\n\r\n               1. Mean resting corrected QT interval (QTc) > 470 ms obtained from 3\r\n                  electrocardiograms (ECGs), using the screening clinic's ECG machine and\r\n                  Fridericia's formula for QT interval correction (QTcF).\r\n\r\n               2. Any clinically important abnormalities in rhythm, conduction, or morphology of\r\n                  the resting ECG (e.g., complete left bundle branch block, third-degree heart\r\n                  block, second-degree heart block, PR interval > 250 ms).\r\n\r\n               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic\r\n                  events, such as heart failure, hypokalemia, congenital long QT syndrome, family\r\n                  history of long QT syndrome, or unexplained sudden death under 40 years of age in\r\n                  first degree relatives or any concomitant medication known to prolong the QT\r\n                  interval.\r\n\r\n               4. Left ventricular ejection fraction (LVEF) < 50%. 6. Any evidence of severe or\r\n                  uncontrolled systemic diseases (including uncontrolled hypertension and active\r\n                  bleeding diatheses) or active infection. Screening for chronic conditions is not\r\n                  required.\r\n\r\n                  7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability\r\n                  to swallow the study drug, or previous significant bowel resection that would\r\n                  preclude adequate absorption of Aumolertinib.\r\n\r\n                  8. Past medical history of interstitial lung disease, drug-induced interstitial\r\n                  lung disease, radiation pneumonitis that required steroid treatment, or any\r\n                  evidence of clinically active interstitial lung disease.\r\n\r\n                  9. Women who are breastfeeding or have a positive urine or serum pregnancy test\r\n                  at the Screening Visit.\r\n\r\n                  10. History of hypersensitivity to any active or inactive ingredient of study\r\n                  drugs (pemetrexed, cisplatin, carboplatin, Aumolertinib) or to drugs with a\r\n                  similar chemical structure or class to Aumolertinib.\r\n\r\n                  11. Judgment by the investigator that the patient should not participate in the\r\n                  study if the patient is unlikely to comply with study procedures, restrictions,\r\n                  and requirements.\r\n\r\n                  12. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's\r\n                  opinion, present a specific risk to the patient's safety.\r\n\r\n                  13. Any disease or condition that, in the opinion of the investigator, would\r\n                  compromise the safety of the patient or interfere with study assessments.\r\n      ","sponsor":"Jiangsu Hansoh Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Aumolertinib","description":"Aumolertinib 110 mg QD in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of every 21-day cycles up to 4~6 cycles, followed by Aumolertinib daily with pemetrexed maintenance (500 mg/m2) on Day 1 of every 21-day cycles.\r\nDose may be reduced to allow for the management of investigational drug related toxicity."},{"intervention_type":"Drug","name":"Drug: Placebo Aumolertinib","description":"Placebo Aumolertinib 110 mg QD Dose may be reduced to allow for the management of investigational drug related toxicity."}],"outcomes":[{"outcome_type":"primary","measure":"PFS (Progression Free Survival) assessed by IRC (Independent Review Committee)","time_frame":"From the time of randomization to disease progression or death, approximately 3 years.","description":"IRC-PFS is defined as the time from randomization until the date of objective disease progression based on IRC assessment or death (by any cause in the absence of progression). The patients will receive long-term follow-up including chest and abdominal CT every 6 weeks until Week 18, then every 12 weeks and onwards."},{"outcome_type":"secondary","measure":"ORR (Objective Response Rate) assessed by IRC (Independent Review Committee)","time_frame":"From the time of randomization to the date of first occurrence of complete response (CR) or partial response (PR), approximately 3 years.","description":"ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression."},{"outcome_type":"secondary","measure":"DoR (Duration of response)","time_frame":"From the time of randomization to disease progression or death, approximately 3 years.","description":"DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression."},{"outcome_type":"secondary","measure":"DCR (Disease Control Rate)","time_frame":"From the time of randomization to disease progression or death, approximately 3 years.","description":"The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD."},{"outcome_type":"secondary","measure":"DepOR (Depth of Response)","time_frame":"From the time of randomization to disease progression or death, approximately 3 years.","description":"DepOR is defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions."},{"outcome_type":"secondary","measure":"PFS (Progression Free Survival) Rate at 12, 18, 24, and 36 months","time_frame":"The PFS Rate at 12, 18, 24, and 36 months is assessed up to 36 months.","description":"PFS Rate at 12, 18, 24, and 36 months is defined as proportion of progression free survival at 12, 18, 24, and 36 months from the date of randomization."},{"outcome_type":"secondary","measure":"OS (Overall survival)","time_frame":"From the time of randomization to death due to any cause, approximately 6 years.","description":"Overall survival (OS) is defined as the time from randomization to death due to any cause. The survival will be followed up with telephone every 12 weeks after discontinuation of the randomized treatment."},{"outcome_type":"secondary","measure":"OS (Overall survival) rate at 3, 5 years","time_frame":"The OS rate at 3, 5 years is assessed up to 5 years.","description":"OS rate at 3, 5 years is defined as the proportion of patients alive at 3, 5 years from the date of randomization."},{"outcome_type":"secondary","measure":"Incidence and severity of AEs (Adverse Events)","time_frame":"From the screening period to 28 days after treatment completion, approximately 4 years.","description":"AEs are graded according to CTCAE v5.0 and recorded in the case report form."}]}
{"nct_id":"NCT04886700","start_date":"2021-08-01","phase":"Phase 2","enrollment":104,"brief_title":"Study of the SG001 Injection for Patients With Relapsed or Metastatic Uterine Cervical Cancer","official_title":"A Single-arm, Open-label, Multicenter, Phase II Study for Evaluation of Efficacy and Safety of the SG001 Injection for Patients With PD-L1-positive Relapsed or Metastatic Uterine Cervical Cancer","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-12-31","last_update":"2021-05-14","description":"This study is an open, single-arm, multicenter phase II study to investigate the efficacy and safety of SG001 for relapsed or metastatic uterine cervical cancer patients with PD-L1 positive (CPS1), and has failed at least first line platinum-based chemotherapy.","other_id":"SYSA1802-CSP-004","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Age  18 on the day of signing informed consent and volunteered to participated in\r\n             this study.\r\n\r\n          -  2. Histologically documented relapsed or metastatic uterine cervical cancer including\r\n             squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, a relevant\r\n             pathological report must also be provided.\r\n\r\n          -  3. Relapsed or metastatic uterine cervical cancer patient who has failed at least\r\n             first line platinum-based chemotherapy, which means having disease progression during\r\n             or following at least first line platinum based chemotherapy or for which platinum\r\n             based chemotherapy is not tolerated, having disease progression within 6 months of or\r\n             during neoadjuvant or adjuvant treatment with platinum based chemotherapy can also be\r\n             accepted.\r\n\r\n          -  4. Programmed Cell Death Ligand 1 (PD-L1) positive expression defined by Combined\r\n             Positive Score (CPS) 1.\r\n\r\n          -  5. All the subjects should have at least one measurable lesion in CT or MRI test\r\n             assessed by RECIST 1.1. A previously irradiated site lesion could only be counted as a\r\n             target lesion if there was clear sign of progression since the irradiation.\r\n\r\n          -  6. If subjects have received anti-tumor therapies before, the toxicity severity must\r\n             decrease to  Grade1 evaluated by NCI-CTCAE 5.0, except for residual alopecia or\r\n             fatigue.\r\n\r\n          -  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  8. Has a predicted survival period  3 months assessed by investigators.\r\n\r\n          -  9. Demonstrate adequate organ function as defined below:\r\n\r\n               1. Blood routine tests (No blood transfusions were performed, no hematopoietic\r\n                  stimulators were used, and no drugs were used to correct blood cell counts ):\r\n                  Absolute neutrophil count (ANC) 1.5109/L; Platelets 75109/L; Hemoglobin\r\n                  (HGB)9 g/dL;\r\n\r\n               2. Serum biochemical indexs: Serum creatinine 1.5 X ULN or Creatinine clearance\r\n                  (CCr)  50mL/min; Serum total bilirubin (TBIL)  1.5 X upper limit of normal ULN\r\n                  (Subjects with Gilbert's syndrome can be up to 3 x ULN); Aspartate\r\n                  aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 X ULN or 5 X ULN\r\n                  for subjects with hepatocellular carcinoma and liver metastases;\r\n\r\n               3. Coagulation function: Activated partial thromboplastin time (APPT) and\r\n                  International Normalized Ratio (INR)1.5 X ULN (No anticoagulants or other drugs\r\n                  affecting clotting function were used within 14 days prior to the first\r\n                  administration, except for subjects requiring long-term anticoagulant therapy).\r\n\r\n          -  10. Women of child-bearing potential (WOCBP) should be willing to use reliable\r\n             contraceptive methods from signing the informed consent form to 6 months after last\r\n             dose of investigational drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  1. History of allergic reactions attributed to any monoclonal antibody, and\r\n             uncontrolled history of allergic asthma.\r\n\r\n          -  2. Patients with other types of malignant tumours that have progressed or require\r\n             treatment within 5 years prior to the screening, but well-treated skin basal cell\r\n             carcinoma, skin squamous cell carcinoma, or superficial bladder cancer, and having\r\n             cured carcinoma in situ, e.g. breast carcinoma in situ, can be accepted.\r\n\r\n          -  3. Patients with any active autoimmune disease, but subjects with following diseases\r\n             are allowed for further screening: subjects with well-controlled type I diabetes,\r\n             well-controlled hypothyroidism with hormone replacement therapy, skin diseases (such\r\n             as vitiligo, psoriasis, or hair loss) without systemic treatment, or who are not\r\n             expected to relapse without external triggers.\r\n\r\n          -  4. History of primary immunodeficiency.\r\n\r\n          -  5. Patients with serious cardiovascular diseases, such as grade 2 or above heart\r\n             failure based on the NYHA (New York Heart Association) Class guidelines, previous\r\n             myocardial infarction within 3 months, poorly controlled arrhythmias or unstable\r\n             angina pectoris, previous arterial or venous thrombosis events within 3 months (e.g.\r\n             transient ischemic attack, cerebral hemorrhage, cerebral infarction, deep vein\r\n             thrombosis and pulmonary embolism).\r\n\r\n          -  6. Has history of Interstitial Lung Disease (Patients caused by radiotherapy are\r\n             eligible), or non-infectious pneumonitis need for glucocorticoid therapy.\r\n\r\n          -  7. Have a history of active tuberculosis.\r\n\r\n          -  8. Subjects with untreated or treated but still symptomatic central nervous system\r\n             metastases (except for residual signs or symptoms related to CNS treatment, those with\r\n             stable or improved neurological symptoms at least 2 weeks prior to screening can be\r\n             included).\r\n\r\n          -  9. Prior therapy with any other antibody or drug specifically targeting T-cell\r\n             co-stimulation or checkpoint pathways including anti-PD-1, anti-PD-L1, anti CTLA-4,\r\n             OX40 agonist, and anti-CD137, etc.\r\n\r\n          -  10. Immune-related adverse events of grade 3 or higherNCI-CTCAE 5.0after immune\r\n             therapy.\r\n\r\n          -  11. Have received major surgery or radical radiotherapy within 28 days, or palliative\r\n             radiotherapy within 14 days, or radiological agents (strontium, samarium, etc.) within\r\n             56 days prior to screening.\r\n\r\n          -  12. Have received systemic anti-tumour therapy 28 days before the first dose,\r\n             including but not limited to chemotherapy, immunotherapy, macromolecular targeted\r\n             therapy, and biological therapy (tumour vaccine, cytokines or growth factors\r\n             controlling cancer); Patients who received small-molecule targeted and oral\r\n             fluorouracil therapy within 14 days before the first dose.\r\n\r\n          -  13. Have received attenuated live vaccine within 28 days before the first dose or\r\n             planned to receive during the study period.\r\n\r\n          -  14. Have received Chinese herbal medicine or Chinese patent medicine with anti-tumor\r\n             activity within14 days prior to the first dose.\r\n\r\n          -  15. Any active infection requiring systemic treatment by intravenous infusion within\r\n             28 days prior to the first dose.\r\n\r\n          -  16. Have received systemic corticosteroids (at doses equivalent to or greater than 10\r\n             mg/day of prednisone) or other immunosuppressive drugs within 14 days prior to the\r\n             first dose of study drug.\r\n\r\n          -  17. Have participated other clinical trials and received related investigated drugs\r\n             within 28 days prior to the first dose of study drug (counted from the date of the\r\n             last treatment in the previous clinical trial, patients participated in the overall\r\n             survival follow-up of the previous clinical trial can be accepted).\r\n\r\n          -  18. Patients should be excluded if they have a positive test for human\r\n             immunodeficiency virus antibody (HIV-Ab) or treponema pallidum antibody (TP-Ab).\r\n             Patients with positive Hepatitis B virus surface antigen (HBsAg) and/or hepatitis B\r\n             virus core antibody (HBcAb) as well quantitative HBV-DNA above upper limit of normal\r\n             value, and patients with positive hepatitis C virus antibody (HCV-Ab) as well\r\n             quantitative HCV-RNA above upper limit of normal value, should also be excluded.\r\n\r\n          -  19. Pregnant or lactating women; Or the blood pregnancy test of women at child-bearing\r\n             age is positive during screening.\r\n\r\n          -  20. Other conditions that may increase the risk of drug use in the study, or interfere\r\n             with the interpretation of the study results, or affect the compliance of the study,\r\n             etc.\r\n      ","sponsor":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd.","sponsor_type":"Industry","conditions":"Uterine Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SG001","description":"Subjects will receive intravenous infusion of SG001 at the dose of 240 mg every 2 weeks until disease progression, unacceptable toxicity, meeting the suspension or termination criteria, or up to 24 months in patients without disease progression."}],"outcomes":[{"outcome_type":"secondary","measure":"Population pharmacokinetic parameter exposure-response relationship.","time_frame":"At the end of cycle 7 (every cycle is 14 days).","description":"The pharmacokinetic profile of SG001."},{"outcome_type":"primary","measure":"Objective response rate (ORR) by RECIST1.1 in relapsed or metastatic uterine cervical cancer evaluated by IRC (Independent Review Committee), confirmation of CR and PR is required in at least 4 weeks after initial documentation.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"ORR (objective response rate) evaluated by investigators.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"DOR (duration of response) evaluated by IRC.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"DCR (disease control rate) evaluated by IRC.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"PFS (free-progression survival) evaluated by IRC.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"OS (overall survival) evaluated by IRC.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"TTR (time to response) evaluated by IRC.","time_frame":"From first dose to the first documented progression of disease, subject withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest, assessed up to 24 months.","description":"To investigate the efficacy of SG001 in relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"Amount, severity, and duration of TEAEs (treatment emergent adverse event) evaluated by NCI-CTCAE V5.0.","time_frame":"From the date of signing Informed Consent Form (ICF) up to 28 days following the last dose of study drug, immune related adverse events will be recorded until 90 days after the last dose.","description":"To investigate the safety and tolerance profile of SG001 in patients with relapsed or metastatic uterine cervical cancer."},{"outcome_type":"secondary","measure":"Population pharmacokinetic parameter IIV (interindividual variability).","time_frame":"At the end of cycle 7 (every cycle is 14 days).","description":"The pharmacokinetic profile of SG001."},{"outcome_type":"secondary","measure":"Immunogenicity of SG001, such as anti-drug antibody and neutralizing antibody.","time_frame":"From the first dose of study drug to the end of treatment visit, up to 24 months.","description":"To investigate the immune profile of SG001."}]}
{"nct_id":"NCT04828616","start_date":"2021-07-31","phase":"Phase 2","enrollment":104,"brief_title":"Study of DP303c Injection in Patients With Advanced Ovarian Cancer","official_title":"An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With HER2-expressing Advanced Ovarian Cancer","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-07-31","last_update":"2021-04-02","description":"This study is an open-label, multicentre, phase II study to evaluate the efficacy and safety of of DP303c injection in patients with HER2-expressing advanced ovarian cancer.","other_id":"SYSA1501-CSP-002","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Voluntary agreement to provide written informed consent.\r\n\r\n          2. Aged 18 to 75 years, female.\r\n\r\n          3. Histologically or cytologically confirmed epithelial ovarian cancer, carcinoma tubae,\r\n             or primary peritoneal carcinoma.\r\n\r\n          4. Patients have previously received platinum-containing chemotherapy.\r\n\r\n          5. Patients must provide tissue samples that are certified as qualified by the central\r\n             laboratory, and the HER2 status of the tissue samples is determined by the central\r\n             laboratory:Part1: HER2 overexpressing: IHC 2+ or IHC 3+; Part2a: HER2 overexpressing:\r\n             IHC 2+ or IHC 3+; Part2b: HER2 low expressing: IHC1+;\r\n\r\n          6. The Eastern Cooperative Oncology Group (ECOG) score is 0 to 2, and life expectancy  3\r\n             months.\r\n\r\n          7. At least one measurable lesion at baseline per RECIST v1.1.\r\n\r\n          8. The function of major organs must meet the following criteria within 7 days before\r\n             enrollment (Have not received blood transfusion, EPO, G-CSF or other medical\r\n             supportive treatment within 14 days before the first dose of study drug):\r\n\r\n             Absolute neutrophil count (ANC) 1.5109/L, Platelet 100109 /L; Hemoglobin 90 g/L\r\n             or 5.6 mmol/L; International normalized ratio (INR) or prothrombin time (PT)\r\n             1.5ULN; Activated Partial Thromboplastin Time (APTT) 1.5ULN; Creatinine clearance\r\n             rate 30 mL/min (Calculated by Cockcroft-Gualt formula); Total bilirubin 1.5ULN or\r\n             3ULN for patients with Gilbert's syndrome or liver metastasis: Aspartate\r\n             aminotransferase (AST) and Alanine aminotransferase (ALT) 2.5ULN or 5ULN for\r\n             patients with liver metastasis:\r\n\r\n          9. Female patient of childbearing age must agree to take adequate contraceptive measures\r\n             during the entire study period and through at least 6 months after the last dose of\r\n             study drug. Women of childbearing age must have a negative pregnancy test within 7\r\n             days before study entry.\r\n\r\n         10. Patients will be able to communicate well with the investigator, understand and comply\r\n             with the requirements of the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Pregnant or breastfeeding women.\r\n\r\n          2. Has not recovered from adverse reactions caused by previous anti-tumor treatments to \r\n             grade 1 or baseline (refer to NCI CTCAE 5.0), except for alopecia, pigmentation and\r\n             other toxicity judged no safety risk by the investigator .\r\n\r\n          3. Patients who have previously received trastuzumab or trastuzumab analogues that have\r\n             related toxicity, resulting in permanent discontinuation.\r\n\r\n          4. Patients with allergic history or delayed allergic reaction to any components\r\n             (trastuzumab analogues, MMAE, sodium citrate dihydrate, citrate monohydrate,\r\n             polysorbate 20 and sucrose, etc.) of DP303c.\r\n\r\n          5. Patients with brain or pia mater metastasis, except for patients with central nervous\r\n             system (CNS) metastases in the following conditions: untreated but asymptomatic, or\r\n             progression-free status in imaging evidence for at least 4 weeks after treatment and\r\n             not requiring hormone therapy for at least 4 weeks.\r\n\r\n          6. Chemotherapy, radiotherapy, biotherapy, targeted therapy, immunotherapy and other\r\n             anti-tumor treatments within 4 weeks before the first dose of study drug, 6 weeks for\r\n             nitrosourea (such as carmustine, lomustine, etc.) or mitomycin C, 5 half-lives for\r\n             oral fluorouracil and small molecule targeted drugs, 2 weeks for endocrine therapy and\r\n             Chinese medicine treatment with anti-tumor indications; or local palliative\r\n             radiotherapy for bone metastasis and pain relief within 2 weeks.\r\n\r\n          7. People who currently have corneal diseases that require medication or surgical\r\n             intervention, or have a history of serious corneal diseases, or are unwilling to stop\r\n             wearing contact lenses during the study.\r\n\r\n          8. History of any other malignant tumors within five years (except for skin basal cell\r\n             carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate\r\n             cancer, cervical cancer in situ, stage I ductal carcinoma in situ and stage I grade 1\r\n             endometrial carcinoma that have been radically removed and have not recurred; breast\r\n             cancer with no recurrence for more than 3 years after radical operation).\r\n\r\n          9. History of (non-infectious) interstitial lung disease (ILD)/pulmonary disease that\r\n             required steroids, or current ILD/pulmonary disease, or suspected ILD/ pulmonary\r\n             disease that cannot be excluded by imaging examination; except for patients with\r\n             radiation pneumonitis without clinical symptoms after 3 months of radiotherapy.\r\n\r\n         10. Patients with dyspnea at rest induced by complications of advanced malignant tumors or\r\n             need for continuous oxygen therapy.\r\n\r\n         11. Patients with complete intestinal obstruction, or pleural effusions or ascites that\r\n             are difficult to control within 4 weeks before entry (the frequency of percutaneous\r\n             drainage is more than twice a week, or continuous drainage daily volume is  1000 mL).\r\n\r\n         12. Patients with serious cardiovascular and cerebrovascular diseases, including but not\r\n             limited to:\r\n\r\n               -  Uncontrolled angina, congestive heart failure (NYHA III-IV), myocardial\r\n                  infarction or severe arrhythmia within 6 months before enrollment;\r\n\r\n               -  Left ventricular ejection fraction (LVEF) <50% or lower limit of normal in\r\n                  echocardiogram (ECHO) or multi-gate detection scan (MUGA);\r\n\r\n               -  Average adjusted QT interval prolongation >470 ms, QT interval corrected by\r\n                  Fridericia's formula (QTcF).\r\n\r\n         13. The cumulative amount of previous exposure to anthracyclines has reached the following\r\n             doses: doxorubicin or liposomal doxorubicin>500 mg/m2; epirubicin>900 mg/m2;\r\n             mitoxantrone>120 mg/m2; Others (liposomal doxorubicin or other anthracyclines is\r\n             equivalent to a dose of > 500 mg/m2 adriamycin); if more than one anthracycline is\r\n             used, the cumulative dose is equivalent to a total dose of >500 mg/m2 adriamycin.\r\n\r\n         14. Peripheral neuropathy grade 2 before entry (NCI CTCAE 5.0).\r\n\r\n         15. Uncontrollable electrolyte imbalances include hypokalemia, hypocalcemia or\r\n             hypomagnesemia (refer to NCI CTCAE 5.0, 2 grade).\r\n\r\n         16. HIV positive, or syphilis infection requiring systematic treatment.\r\n\r\n         17. Patients with active hepatitis B or C (HBsAg positive, with HBV DNA positive, and the\r\n             ALT continues to be higher than the upper limit of normal, without other causes of ALT\r\n             elevation; HCVAb positive with HCV RNA higher than the upper limit of normal).\r\n\r\n         18. Patients have used strong CYP3A4 inhibitors or CYP3A4 strong inducers with a washout\r\n             period less than 28 days or 5 half-lives (whichever is shorter) before the first dose\r\n             of the study drug.\r\n\r\n         19. Patients underwent major surgery within 4 weeks and did not fully recover before the\r\n             first dose of study drug.\r\n\r\n         20. Patients have received other clinical trial drugs within 4 weeks before the first dose\r\n             of study drug.\r\n\r\n         21. Have previously received antibody drug conjugate targeting HER2.\r\n\r\n         22. Patients with any mental or cognitive impairment that may restrict their understanding\r\n             and implementation of the informed consent form.\r\n\r\n         23. Other serious or uncontrollable diseases or conditions that may affect the evaluation\r\n             of the primary endpoint or the investigator believes that participation in this study\r\n             may bring risks to the patient.\r\n      ","sponsor":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd.","sponsor_type":"Industry","conditions":"Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: DP303c injection","description":"DP303c injection, every 3 weeks (Q3W)"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate(ORR)","time_frame":"Through study completion, an average of 3 year","description":"Objective Response Rate is defined as the percentage of patients with a complete response (CR) or partial response (PR)."},{"outcome_type":"secondary","measure":"PFS","time_frame":"Through study completion, an average of 3 year","description":"Progression Free Survival"},{"outcome_type":"secondary","measure":"OS","time_frame":"From the enrollment to the death of last subject or the end of the clinical trial (assessed up to 36 months)","description":"Overall Survival"},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Through study completion, an average of 3 year","description":"To preliminarily evaluate DoR in patients with advanced solid tumors"},{"outcome_type":"secondary","measure":"Incidence of adverse events (AEs) and serious adverse events (SAEs)","time_frame":"Through study completion, an average of 3 year","description":"The drug safety will be assessed by investigator(s) according to NCI-CTCAE v5.0."},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax) of DP303c","time_frame":"Part1:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15,Cycle 3 Day 1and Cycle 5 Day 1;Part2:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15; predose. A cycle is 21 days","description":"The pharmacokinetics(PK) profile of DP303c"},{"outcome_type":"secondary","measure":"Time of peak plasma concentration (Tmax)","time_frame":"Part1:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15,Cycle 3 Day 1and Cycle 5 Day 1;Part2:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15; predose. A cycle is 21 days","description":"The pharmacokinetics(PK) profile of DP303c"},{"outcome_type":"secondary","measure":"Area under the plasma concentration time curve (AUC) of DP303c","time_frame":"Part1:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15,Cycle 3 Day 1and Cycle 5 Day 1;Part2:Cycle 1 Day 1, Cycle 1 Day 8,Cycle 1 Day 15, Cycle 2 Day 1 ,Cycle 2 Day 15; predose. A cycle is 21 days","description":"The pharmacokinetics(PK) profile of DP303c"},{"outcome_type":"secondary","measure":"Immunogenicity (anti-drug antibody ADA)","time_frame":"Through study completion, an average of 3 year","description":"Percentage of patients producing detectable ADA."}]}
{"nct_id":"NCT04607642","start_date":"2021-07-31","phase":"Phase 2","enrollment":162,"brief_title":"Trial of BMX-001 or Placebo in Head and Neck Cancer Patients","official_title":"A Randomized, Blinded, Placebo Controlled Phase 2 Trial of Concurrent Radiation Therapy and Cisplatin With and Without BMX-001 in Patients With Locally Advanced Head and Neck Cancer","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-07-31","last_update":"2021-01-27","description":"There are an estimated 65,000 newly diagnosed cases of head and neck cancer each year in the United States. The most common treatment for head and neck cancers is radiotherapy in combination with cisplatin chemotherapy. This treatment regimen is effective in killing the tumor; however, the normal tissues that line the mouth and throat can sustain severe injury from the radiation. Side-effects incurred during irradiation include: mucositis, xerostomia, swelling, trouble swallowing, pain, infections, cavities, hair loss and reddening of the skin. Some of these side effects can be so severe that patients require feeding tubes and management of severe pain can lead to the premature halt of radiotherapy. There are currently no effective radio-protectors used to ameliorate these severe side-effects. BioMimetix has developed small molecular weight superoxide dismutase (SOD) mimetic, BMX-001, that is a very potent radio-protector of head and neck tissues. In our first clinical trial in a head and neck cancer patient cohort using this drug, we have early evidence that BMX-001 may protect against radiation-induced mucositis and xerostomia. This will be a randomized, placebo-controlled Phase 2 clinical trial to study the effects of BMX-001 (14 mg/subject biw) + radiation therapy + cisplatin against placebo + radiation therapy + cisplatin in prevention of acute and chronic mucositis and xerostomia.","other_id":"BMX-HN-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Pathologically confirmed (histologically or cytologically) diagnosis of squamous cell\r\n             carcinoma of the oropharynx, larynx, hypopharynx, nasopharyngeal, or oral cavity with\r\n             clinical or pathologic high-risk features who will be receiving radiation and\r\n             concurrent cisplatin chemotherapy.\r\n\r\n          2. Treatment plan to receive a continuous course of IMRT delivered as single daily\r\n             fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy\r\n             depending on whether patients are receiving post-operative or definitive intent\r\n             therapy respectively.\r\n\r\n          3. For patients undergoing curative intent resection, Patients must have undergone gross\r\n             total surgical resection within 56 days prior to registration and beginning of therapy\r\n             under the clinical trial.\r\n\r\n          4. General history and physical examination by a qualified head and neck cancer\r\n             specialist and physician within 8 weeks prior to enrollment (including fiberoptic\r\n             endoscopy).\r\n\r\n          5. Axial imaging of the neck and chest- CT, MRI and/or PET/CT is acceptable, within 8\r\n             weeks prior to date of consent.\r\n\r\n          6. Age  18 years.\r\n\r\n          7. Zubrod Performance Status 0-2 within 4 weeks prior to enrollment.\r\n\r\n          8. CBC/differential obtained within 2 weeks prior to starting the study drug with\r\n             adequate bone marrow function\r\n\r\n          9. Adequate hepatic function\r\n\r\n         10. Adequate renal function defined as follows:\r\n\r\n         11. Patient must be willing and able to follow study procedures and instructions.\r\n\r\n         12. Patient must provide study-specific informed consent within 28 days prior to starting\r\n             the study drug.\r\n\r\n         13. Negative pregnancy test for women of child-bearing potential within 48 hours prior to\r\n             first dose of BMX-001.\r\n\r\n         14. Women of childbearing potential and male participants must agree to use a medically\r\n             effective means of birth control throughout their participation in the treatment phase\r\n             of the study and until 12 months following the last study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Distant metastasis\r\n\r\n          2. Hypertension\r\n\r\n          3. Grade 2 hypotension at screening\r\n\r\n          4. Concurrent treatment with nitrates or other drugs that may, in the judgment of the\r\n             treating investigator, create a risk for a precipitous decrease in blood pressure\r\n\r\n          5. History of syncope within the last 6 months\r\n\r\n          6. Patients receiving, or unable to stop use of prohibited medications\r\n\r\n          7. Pregnancy or women of childbearing potential and men who are sexually active and not\r\n             willing/able to use medically acceptable forms of contraception\r\n\r\n          8. Women who are breast feeding are not eligible\r\n\r\n          9. Known hypersensitivity to compounds of similar chemical composition to BMX-001\r\n\r\n         10. Grade 3-4 electrolyte abnormalities (CTCAE v 5.0)\r\n\r\n         11. Prior unrelated malignancy requiring current active treatment with exceptions\r\n\r\n         12. Prior history of HNSCC receiving radiation or chemo-radiation.\r\n\r\n         13. Prior systemic chemotherapy for the study cancer (including neoadjuvant chemotherapy);\r\n             note that prior chemotherapy for a different cancer is allowable.\r\n\r\n         14. Prior radiotherapy that would result in overlap of radiation treatment fields with\r\n             planned treatment for study cancer.\r\n\r\n         15. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a\r\n             QTc interval >480 milliseconds (ms) using the specific/usual choice by clinical center\r\n             for correction factor.\r\n\r\n         16. A history of additional risk factors for TdP\r\n\r\n         17. Severe, active co-morbidity as defined in the protocol\r\n      ","sponsor":"BioMimetix JV, LLC","sponsor_type":"Industry","conditions":"Head and Neck Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: BMX-001","description":"BMX-001 consists of a porphyrin ring with pyridyl groups attached at each of the four methane bridge carbons. The nitrogen in the pyridyl ring is at the 2 position and has a side chain consisting of six carbons with an ether linkage. A manganese atom is chelated into the porphyrin ring and is the active center of the molecule. This molecule is an enzymatic scavenger of free radical species operating at close to diffusion-limited rates."},{"intervention_type":"Radiation","name":"Radiation: Radiation Therapy","description":"Treatment plan should include a continuous course of treatment delivered as single daily fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy. Planned radiation treatment volumes must include at least two oral mucosal sub-sites (buccal mucosa, retromolar trigone, floor of mouth, tongue, soft palate, hard palate) with a portion of each site receiving at least 50 Gy."},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Cisplatin is an IV chemotherapeutic agent approved to treat head and neck cancers. Cisplatin will be administered per institution's standard of care practice. Common standard of care practice includes dosing cisplatin at 100mg/m2 IV q21 days starting on Day 1 of RT for 2-3 doses or dosing cisplatin at 40 mg/m2 IV each week of RT for 6-7 total doses. Cisplatin will be infused per institutional guidelines."},{"intervention_type":"Other","name":"Other: Placebo","description":"The placebo to be used in this study is 0.9% Sodium Chloride Injection, USP."}],"outcomes":[{"outcome_type":"secondary","measure":"Disease Free Survival","time_frame":"2 years","description":"Disease-free survival (DFS), defined as the interval (measured in days) from the date of randomization until the date of CT scan showing tumor progression."},{"outcome_type":"primary","measure":"Mucositis Incidence","time_frame":"12 weeks","description":"The primary outcome measure used for each study subject is a dichotomous measure of whether they experienced severe oral mucositis (OM, defined as grade 3 or 4 according to WHO criteria) at any time between the first IMRT fraction until 30 days after the completion of RT. The primary analysis will thus test the difference in the proportion of subjects from each treatment group who experience severe OM."},{"outcome_type":"secondary","measure":"Mucositis Duration","time_frame":"12 weeks","description":"The interval (measured in days) from the date of first determination of severe OM to the date of the first determination of not having severe OM, without a subsequent instance of severe OM."},{"outcome_type":"secondary","measure":"Mucositis Severity","time_frame":"12 weeks","description":"Days it takes for patients in each arm to develop severe oral mucositis."},{"outcome_type":"secondary","measure":"Xerostomia Incidence","time_frame":"1, 6, 12, and 24 months","description":"The dichotomous measure of whether the study subject had grade 2 (or greater) Xerostomia (as defined by CTCAE v 5.0). This will be assessed at 1, 6, 12, and 24 months after completion of RT."},{"outcome_type":"secondary","measure":"Saliva Production Measurements","time_frame":"1, 6, 12, and 24 months","description":"The continuous measure of saliva production (g/min), measured at baseline and 1, 6, 12, and 24 months after completion of RT. Both stimulated and unstimulated saliva production will be measured."},{"outcome_type":"secondary","measure":"Radiation Dermatitis Duration","time_frame":"12 weeks","description":"The continuous endpoint of duration of radiation dermatitis, where duration is defined as the interval (measured in days) from the date of first determination of radiation dermatitis to the date of the first determination of not having radiation dermatitis, without a subsequent instance of radiation dermatitis. For any subject whose radiation dermatitis persists, the final date will be 30 days after the completion of RT."},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"2 years","description":"Overall survival (OS), defined as the interval (measured in days) from the date of randomization until the date of death from any cause."}]}
{"nct_id":"NCT04274426","start_date":"2021-07-31","phase":"Phase 2","enrollment":136,"brief_title":"Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FR) High Recurrent Ovarian Cancer","official_title":"A Randomized Phase II Trial of Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FR) High Recurrent Ovarian Cancer Eligible for Platinum-based Chemotherapy.","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-01-31","last_update":"2021-07-21","description":"This is a multi-center, randomized, two-arm, open-label, comparative phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FR) high recurrent ovarian cancer eligible for platinum-based chemotherapy.","other_id":"AGO-OVAR 2.34","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. All patients must have a pathologically documented, definite diagnosis of epithelial\r\n             cancer of the ovary, the fallopian tube or the peritoneum\r\n\r\n          2. Relapsed disease with a platinum-free interval >3 months\r\n\r\n          3. All histologic subtypes of ovarian carcinoma including carcinosarcoma (malignant mixed\r\n             Mullerian tumors, MMMT)\r\n\r\n          4. Patients with wildtype BRCA1/2 mutation status or with a deleterious BRCA1/2 mutation\r\n             in germline or somatic testing if they underwent PARP inhibitor therapy in previous\r\n             treatment line.\r\n\r\n          5. Patients must be willing to provide archival tumor tissue from current relapse or\r\n             previous surgeries/biopsies for central confirmation of FR high status by PS2+\r\n             scoring:\r\n\r\n             all tumors must exhibit 75% of tumor cells with FR membrane staining and  2+\r\n             intensity by immunohistochemistry (IHC) using the Ventana FOLR1 (FOLR1 2.1) CDx assay.\r\n\r\n          6. Patients must have measurable disease or evaluable disease in combination with GCIG\r\n             CA-125 criteria.\r\n\r\n          7. Patients had one or more prior lines of chemotherapy. The last line of chemotherapy\r\n             should have included platinum and has resulted in a partial or complete response.\r\n\r\n          8. Major surgery (not including placement of vascular access device, tumor punch/scrape\r\n             biopsies or secondary wound closure) must be completed four weeks prior to Day 1.\r\n\r\n          9. Patients must have adequate hematological, liver, cardiac and kidney function:\r\n\r\n               1. Hemoglobin  10.0 g/dL.\r\n\r\n               2. Absolute neutrophil count (ANC)  1.5 x 109/L\r\n\r\n               3. Platelet count  100 x 109/L.\r\n\r\n               4. Total bilirubin  1.5 x institutional upper limit of normal (ULN).\r\n\r\n               5. Aspartate aminotransferase/Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT))\r\n                  and Alanine aminotransferase/Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) \r\n                  2.5 x ULN, unless liver metastases are present in which case they must be  5 x\r\n                  ULN.\r\n\r\n               6. Serum creatinine  1.5 x institutional ULN and glomerular filtration rate of at\r\n                  least 40 ml/minute according to Cockroft-Gault formula.\r\n\r\n         10. Patient is female and 18 years of age at the time of the first screening visit.\r\n\r\n         11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.\r\n\r\n         12. Patients must be willing and able to sign the informed consent form, and to adhere to\r\n             the study visit schedule and other protocol requirements.\r\n\r\n         13. Women of childbearing potential (a woman is considered of childbearing potential\r\n             (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless\r\n             permanently ster-ile. Permanent sterilization methods include hysterectomy, bi-lateral\r\n             salpingectomy and bilateral oophorectomy) must have a negative serum pregnancy test\r\n             within 3 days from day 1 of cycle 1 and agree to use a highly effective method of\r\n             contraception while on study treatment and for at least 6 months after end of\r\n             treatment. Such methods include:\r\n\r\n               1. Combined (estrogen and progestogen containing) hor-monal contraception associated\r\n                  with inhibition of ovulation:\r\n\r\n                    -  oral\r\n\r\n                    -  intravaginal\r\n\r\n                    -  transdermal\r\n\r\n               2. Progestogen-only hormonal contraception associated with inhibition of ovulation:\r\n\r\n                    -  oral\r\n\r\n                    -  injectable\r\n\r\n                    -  implantable\r\n\r\n               3. Intrauterine device (IUD)\r\n\r\n               4. Intrauterine hormone-releasing system ( IUS)\r\n\r\n               5. Bilateral tubal occlusion\r\n\r\n               6. Vasectomized partner\r\n\r\n               7. Sexual abstinence\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e.\r\n             germ cell tumors)\r\n\r\n          2. Ovarian tumors of low malignant potential (e.g. borderline tumors).\r\n\r\n          3. Unknown BRCA status.\r\n\r\n          4. Patients who are planned to receive bevacizumab for the current relapse.\r\n\r\n          5. Other malignancy within the last 3 years (except cervix or breast in situ carcinoma,\r\n             type I stage I endometrial cancer)\r\n\r\n          6. Patients who underwent surgery for the current relapse with macroscopic complete\r\n             resection\r\n\r\n          7. Prior systemic anticancer therapy within 28 days before randomization\r\n\r\n          8. Prior treatment with folate receptor-targeting investigational agents is not allowed.\r\n\r\n          9. Patients with > Grade 1 peripheral neuropathy.\r\n\r\n         10. Serious concurrent illness or clinically-relevant active infection\r\n\r\n         11. Previous clinical diagnosis of non-infectious interstitial lung disease, including\r\n             non-infectious pneumonitis.\r\n\r\n         12. Active or chronic corneal disorders such as Sjogren's syndrome, Fuchs corneal\r\n             dystrophy (requiring treatment), history of corneal transplantation, active herpetic\r\n             keratitis, active ocular conditions requiring ongoing treatment/monitoring such as\r\n             uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal\r\n             injections, active diabetic retinopathy with macular edema, macular degeneration,\r\n             presence of papilledema, and /or monocular vision. Active or chronic corneal disorder\r\n\r\n         13. Required use of folate-containing supplements (e.g. folate deficiency)\r\n\r\n         14. Women of childbearing potential (WOCBP) not protected by highly effective\r\n             contraceptive methods.\r\n\r\n         15. Pregnant and/or breast-feeding women.\r\n\r\n         16. Known hypersensitivity to one of the chemotherapy re-gimes and/or PARP inhibitors\r\n             and/or any of their excipients.\r\n\r\n         17. Patients with prior hypersensitivity to monoclonal antibodies.\r\n\r\n         18. Patients with potential risks according to contraindication, warnings or interactions\r\n             of the used chemotherapeutic agents as stated in the SmPCs are not eligible for\r\n             partici-pation in this trial.\r\n\r\n         19. Patients with untreated or symptomatic central nervous system (CNS) metastases\r\n      ","sponsor":"AGO Research GmbH","sponsor_type":"Industry","conditions":"Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Carboplatin will administered by intravenous route"},{"intervention_type":"Drug","name":"Drug: Pegylated liposomal doxorubicin (PLD)","description":"PLD will be administered by intravenous route"},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Gemcitabine will be administered by intravenous route"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Paclitaxel will be administered by intravenous route"},{"intervention_type":"Drug","name":"Drug: Mirvetuximab Soravtansine","description":"Mirvetuximab Soravtansine will be administered by intravenous route"}],"outcomes":[{"outcome_type":"primary","measure":"Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier. PD is based on investigator assess-ment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).","time_frame":"Up to 2.5 years. From date of randomization until date of progressive disease (PD) or death, whichever occurs earlier.","description":"PD is based on investigator assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)."},{"outcome_type":"secondary","measure":"OS","time_frame":"Up to 2.5 years. From date of randomization until date of death from any cause.","description":"Overall survival"},{"outcome_type":"secondary","measure":"ORR","time_frame":"Up to 2.5 years. From date of randomization to date of death death from any cause.","description":"Objective response rate"},{"outcome_type":"secondary","measure":"Efficacy regarding PFS","time_frame":"Up to 2.5 years. From date of randomization to date of death from any cause.","description":"Efficacy regarding Progression Free Survival depending on histologic subtype"},{"outcome_type":"secondary","measure":"Efficacy regarding OS","time_frame":"Up to 2.5 years. From date of randomization to date of death from any cause.","description":"Efficacy regarding Overall Survival depending on histologic subtype"},{"outcome_type":"secondary","measure":"Efficacy regarding ORR","time_frame":"Up to 2.5 years. From date of randomization to date of death from any cause.","description":"Efficacy regarding Objective Response Rate depending on histologic subtype"},{"outcome_type":"secondary","measure":"Serological progressive disease","time_frame":"Up to 2.5 years. From date of randomization to date of death death from any cause.","description":"Time to serological progressive disease according to GCIG criteria"},{"outcome_type":"secondary","measure":"Time to first subsequent treatment (TFST)","time_frame":"Up to 2.5 years. From date of randomization to date of death from any cause.","description":"Time to first subsequent treatment (TFST)"},{"outcome_type":"secondary","measure":"Time to second subsequent treatment (TSST)","time_frame":"Up to 2.5 years. From date of randomization until date of death from any cause.","description":"Time to second subsequent treatment (TSST)"},{"outcome_type":"secondary","measure":"Patient-reported outcomes","time_frame":"Up to 2.5 years. From date of randomization until date of death from any cause.","description":"Quality of Life (EORTC C-30)"},{"outcome_type":"secondary","measure":"Patient-reported outcomes","time_frame":"Up to 2.5 years. From date of randomization until date of death from any cause.","description":"Quality of Life (EORTC OV28)"},{"outcome_type":"secondary","measure":"Safety and tolerability","time_frame":"Up to 2.5 years. From date of randomization until date of death from any cause through study completion.","description":"Safety and tolerability of the used drugs evaluated by NCI CTCAE v5.0"}]}
{"nct_id":"NCT04982237","start_date":"2021-07-30","phase":"Phase 3","enrollment":440,"brief_title":"A Study of AK104 Plus Platinum-containing ChemotherapyBevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer","official_title":"A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer","primary_completion_date":"2025-04-01","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-12-30","last_update":"2021-07-29","description":"This is A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer","other_id":"AK104-303","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. signs the written informed consent form.\r\n\r\n          2. Women aged  18 and  75 years.\r\n\r\n          3. ECOG of 0 or 1.\r\n\r\n          4. Life expectancy  3 months.\r\n\r\n          5. Histologically or cytologically confirmed cervical cancer, not amenable to curative\r\n             surgery or concurrent chemoradiotherapy.\r\n\r\n               1. The histological types include squamous cell carcinoma, adenocarcinoma, or\r\n                  adenosquamous cell carcinoma;\r\n\r\n               2. No prior systemic therapy for persistent, recurrent or metastatic ([FIGO] Stage\r\n                  IVB) disease.\r\n\r\n          6. At least one measurable tumor lesion per RECIST v1.1; lesions at sites previously\r\n             treated with radiotherapy or other loco-regional therapy are not considered as target\r\n             lesions unless the lesion has unequivocal progression or the biopsy is obtained to\r\n             confirm maligancy.\r\n\r\n          7. All subjects must provide archival tumor tissue samples within 2 years prior to\r\n             randomization,or fresh tumor tissue samples obtained by biopsy.\r\n\r\n          8. Subjects must have adequate organ function as assessed in the laboratory tests.\r\n\r\n          9. Female subjects of childbearing potential must have a negative serum pregnancy test\r\n             prior to the first dose. If a female subject of childbearing potential must use\r\n             acceptable effective methods of contraception from screening and must agree to\r\n             continue these precautions until 120 days after the last dose of study drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Subjects with other histopathological types of cervical cancer, such as small cell\r\n             carcinoma, clear cell carcinoma, sarcoma, etc.\r\n\r\n          2. Clinically significant hydronephrosis that cannot be relieved by nephrostomy or\r\n             ureteral stenting as judged by the Investigator.\r\n\r\n          3. Presence of nervous system (CNS) metastases or carcinomatous meningitis;\r\n\r\n          4. Subjects with uncontrollable pleural effusion, pericardial effusion, or ascites\r\n             requiring repeated drainage.\r\n\r\n          5. Patients with other active malignancies within 3 years prior to randomization.\r\n\r\n          6. Patients who have received other prior chemotherapeutic agents.\r\n\r\n          7. Any prior treatments targeting the mechanism of tumor immunity, such as\r\n             anti-angiogenic therapy (e.g., bevacizumab), immune checkpoint inhibitors (e.g.,\r\n             anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), or therapy\r\n             against immune costimulatory factors (e.g., antibodies directed against ICOS, CD40,\r\n             CD137, GITR, OX40 targets, etc).\r\n\r\n          8. Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to\r\n             randomization; or elective major surgical treatment required during the study.\r\n\r\n          9. Active or potentially recurrent autoimmune disease.\r\n\r\n         10. Subjects who require systemic treatment with glucocorticoid (> 10 mg/day of prednisone\r\n             or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior\r\n             to randomization;\r\n\r\n         11. Use of live vaccines within 4 weeks prior to randomization.\r\n\r\n         12. Known primary or secondary immunodeficiencies, including testing positive for human\r\n             immunodeficiency virus (HIV) antibodies.\r\n\r\n         13. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem\r\n             cell transplantation.\r\n\r\n         14. Known history of interstitial lung disease or non-infectious pneumonitis; unless\r\n             induced by radiation therapies.\r\n\r\n         15. Serious infections requiring hospitalization.\r\n\r\n         16. Presence of active infection requiring systemic therapy.\r\n\r\n         17. Subjects with active hepatitis B and active viral hepatitis C.\r\n\r\n         18. Active or documented inflammatory bowel diseases, active diverticulitis.\r\n\r\n         19. Subjects with known history of severe hypersensitivity reactions to other monoclonal\r\n             antibodies.\r\n\r\n         20. Known any contraindication to cisplatin/carboplatin, paclitaxel or allergy to any of\r\n             their ingredients.\r\n\r\n         21. Pregnant or lactating women.\r\n\r\n         22. Any condition that, in the opinion of the Investigator, may result in a risk when\r\n             receiving the study drug.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: AK104","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: paclitaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: carboplatin","description":"iv infusion"},{"intervention_type":"Drug","name":"Drug: cisplatin","description":"iv infusion"},{"intervention_type":"Drug","name":"Drug: bevacizumab","description":"iv infusion"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"iv infusion"}],"outcomes":[{"outcome_type":"primary","measure":"overall survival (OS)","time_frame":"Up to approximately 2 years","description":"OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"primary","measure":"progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1","time_frame":"Up to approximately 2 years","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 2 years","description":"Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 2 years","description":"Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria."},{"outcome_type":"secondary","measure":"Time to Response（TTR Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 2 years"},{"outcome_type":"secondary","measure":"AE","time_frame":"Up to approximately 2 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment"},{"outcome_type":"secondary","measure":"Observed concentrations of AK104","time_frame":"From first dose of AK104 through 90 days after last dose of AK104","description":"The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration"},{"outcome_type":"secondary","measure":"Number of subjects who develop detectable anti-drug antibodies (ADAs)","time_frame":"From first dose of AK104 through 90 days after last dose of AK104","description":"The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)"}]}
{"nct_id":"NCT04874844","start_date":"2021-07-30","phase":"Phase 2/Phase 3","enrollment":420,"brief_title":"JY025 is a First-line Treatment for EGFR Mutated NSCLC Phase II and III Clinical Trials of Efficacy and Safety","official_title":"Recombinant Anti-VEGFR2 Fully Human Monoclonal Antibody (JY025) Injection Combined With Gefitinib/Erlotinib as First-line Treatment Phase II and III Clinical Trials on the Efficacy and Safety of Patients With EGFR-mutant NSCLC","primary_completion_date":"2022-03-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-06-30","last_update":"2021-05-10","description":"The Phase II study is a multi-center, open, dose escalation and dose extension clinical trial. It is planned to enroll 24 patients; the phase III study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. It is planned to enroll 396 patients, including patients with locally advanced or metastatic non-squamous non-small cell lung cancer with EGFR mutations (EGFR 19 exon deletion or 21 exon mutation).","other_id":"DFBT-JY025-NSCLC-2020-30I","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","intervention_model_description":"Phase II single ;Phase III parallel","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  (1) Fully understand the purpose of the experiment, the investigator judges that he\r\n             can abide by the experiment protocol, and voluntarily sign a written informed consent.\r\n\r\n             (2) The age at the time of signing the informed consent is 18 years old, regardless\r\n             of gender.\r\n\r\n             (3) Patients with non-squamous non-small cell lung cancer (NSCLC) diagnosed by\r\n             histology/cytology.\r\n\r\n             (4) According to the TNM staging of UICC 8th edition, it is determined as B (not\r\n             suitable for surgery or radiotherapy)-IV stage NSCLC.\r\n\r\n             (5) The patient has EGFR exon 19 deletion (19del) or 21 exon [L858R] mutation\r\n             confirmed by the central laboratory (only tissue samples are accepted), and it is\r\n             suitable for first-line treatment of EGFR-TKI.\r\n\r\n             (6) Have not received any systemic treatment for non-small cell lung cancer in the\r\n             past, and have not received any EGFR-TKI drug treatment. If the subject has received\r\n             adjuvant/neo-adjuvant therapy and then relapses, but the end of adjuvant/neo-adjuvant\r\n             therapy is more than 6 months after the first dose of this study, the subject can also\r\n             be included in the group.\r\n\r\n             (7) There is at least one measurable lesion based on RECISTv1.1. (8) The ECOG score is\r\n             0~1. (9) The functions of major organs and bone marrow are basically normal. It is\r\n             required that no blood transfusion or hematopoietic stimulating factors have been used\r\n             within 14 days before screening. The laboratory test results are the results within 7\r\n             days before the start of treatment:\r\n\r\n             Cagulation function INR1.5ULN, aPTT1.5ULN (if the subject is receiving\r\n             anticoagulant therapy Treatment, as long as the aPTT is within the expected treatment\r\n             range of anticoagulant drugs);\r\n\r\n             The subject's liver and kidney function meets the following conditions: total\r\n             bilirubin1.5ULN, ALT and AST2.5ULN, if the liver is invaded by tumor, AST and\r\n             ALT5ULN; endogenous creatinine clearance 60mL/min (Cockcroft-Gault formula); urine\r\n             protein is 0 or 1, or urine protein quantitative <1g/24h \r\n\r\n             The blood routine meets: neutrophil count 1.5109/L, platelet 100109/L, hemoglobin\r\n             9g/dL.\r\n\r\n             (10) Adverse reactions caused by previous local treatments, surgery or other\r\n             anti-cancer treatments have recovered to  CTCAE level 1 (except for hair loss).\r\n\r\n             (11) The life expectancy of the patient is> 12 weeks. (12) Take effective\r\n             contraceptive measures throughout the study period until 12 weeks after the last\r\n             medication.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. The patient is positive for EGFR T790M mutation, positive for ALK fusion, or has any\r\n             other co-mutations (a report is required if co-mutation has been tested, and testing\r\n             is not mandatory if it has not been tested).\r\n\r\n          2. Suffered from other malignant tumors other than NSCLC within 5 years or at the same\r\n             time (except cured skin basal cell carcinoma, prostate carcinoma in situ and cervical\r\n             carcinoma in situ).\r\n\r\n          3. Symptomatic central nervous system (CNS) metastasis.\r\n\r\n          4. Received major surgery, needle biopsy or subcutaneous venous access device placement\r\n             within 7 days before the start of study treatment. Any post-operative bleeding or\r\n             wound complications occurred within 2 months before the start of study treatment.\r\n\r\n          5. Before the start of the study treatment, received radiotherapy in the bone marrow area\r\n             25% of the radiotherapy area, received palliative chest radiotherapy within 28 days,\r\n             or received radiotherapy for local relief or prevention of symptoms (such as pain,\r\n             bleeding or obstruction) within 7 days.\r\n\r\n          6. Idiopathic pulmonary fibrosis confirmed by CT/X-ray; X-ray confirmed or had acute lung\r\n             injury,Pneumoconiosis; have or have had radiation pneumonia or drug-induced pneumonia;\r\n             clinically active interstitial lung disease (chronic, stable,Except for asymptomatic\r\n             patients with imaging changes); imaging evidence shows lung cavities.\r\n\r\n          7. Pleural effusion, pericardial effusion, or ascites and need to be drained every other\r\n             week or more frequently.\r\n\r\n          8. Superior vena cava syndrome.\r\n\r\n          9. Patients with any serious and/or uncontrollable diseases, including:\r\n\r\n               -  Major cardiovascular disease (NYHA grade II-IV heart disease, myocardial\r\n                  infarction or under study Stroke occurred within 3 months before the start),\r\n                  unstable angina pectoris, unstable arrhythmia, congenital QT prolonged syndrome,\r\n                  or QTc interval corrected for the screening period> 500ms ( Bazetts formula: QTcB\r\n                  = QT/RR0.5); Past hypertensive crisis or history of hypertensive encephalopathy,\r\n                  hypertension not controlled by drugs (defined as systolic blood pressure 150mmHg\r\n                  and/or diastolic blood pressure >100mmHg);\r\n\r\n                    -  Severe infections that are active or uncontrolled, such as nosocomial\r\n                       infections, bacteremia, severe lung infections, etc.; Patients with severe\r\n                       immunodeficiency (except those related to corticosteroid use), including\r\n                       those who are known to be HIV-positive;  Liver damage: Child-Pugh grade B\r\n                       (or worse) with severe liver cirrhosis; liver cirrhosis with a history of\r\n                       hepatic encephalopathy; clinically significant ascites caused by liver\r\n                       cirrhosis, which requires diuretic and/or puncture treatment; yes History of\r\n                       hepatorenal syndrome.\r\n\r\n         10. Evidence of major coagulopathy or other obvious bleeding tendency:\r\n\r\n               -  Bleeding incidents caused by esophageal and/or gastric varices occurred within 6\r\n                  months before the start of the study treatment;\r\n\r\n                    -  Hemoptysis occurred within 1 month before the start of study treatment (>2.5\r\n                       mL bright red blood each time);\r\n\r\n                         -  Thrombosis or embolism events, major vascular diseases (such as aortic\r\n                            aneurysms that require surgical repair) occurred within 6 months before\r\n                            the start of the study treatment; Current or recent (within 10 days\r\n                            before the start of the study treatment) anticoagulant therapy for\r\n                            therapeutic purposes (except for low molecular weight heparin therapy);\r\n                            Current or recent (within 10 days before the start of the study\r\n                            treatment) use aspirin (>325 mg/d) or ticlopidine, clopidogrel,\r\n                            cilostazol for treatment; Patients with imaging evidence that there\r\n                            are large blood vessels invaded or wrapped, and there is a significant\r\n                            risk of bleeding.\r\n\r\n         11. Abdominal or tracheoesophageal fistula, gastrointestinal perforation, or\r\n             intra-abdominal abscess within 6 months before the start of study treatment.\r\n\r\n         12. Severe, non-healing or dehiscence wounds, active ulcers or untreated fractures.\r\n\r\n         13. There are factors that significantly affect the absorption of oral drugs, such as\r\n             inability to swallow, chronic diarrhea, and intestinal obstruction.\r\n\r\n         14. Being treated with CYP3A4 inducers (such as rifampicin or phenytoin) or strong\r\n             inhibitors (such as itraconazole or ketoconazole).\r\n\r\n         15. Proton pump inhibitors (such as esomeprazole magnesium or omeprazole) need to be used\r\n             daily.\r\n\r\n         16. Any known serious ocular surface disease.\r\n\r\n         17. Those who are known to be allergic to any component of the therapeutic drug, or have a\r\n             history of allergy to monoclonal antibody therapy.\r\n\r\n         18. Previously received allogeneic stem cell or solid organ transplantation.\r\n\r\n         19. The research treatment was conducted within 4 weeks before the start of the research\r\n             treatment.\r\n\r\n         20. Are pregnant or breastfeeding.\r\n\r\n         21. For any other disease, metabolic dysfunction, physical examination or clinical\r\n             laboratory examination to find contraindications to the study drug, the investigator's\r\n             judgment may affect the interpretation of the results, or may put the patient at a\r\n             high risk of treatment complications.\r\n      ","sponsor":"Beijing Dongfang Biotech Co., Ltd.","sponsor_type":"Industry","conditions":"NSCLC","interventions":[{"intervention_type":"Biological","name":"Biological: Recombinant anti-VEGFR2 fully human monoclonal antibody (JY025)","description":"The ratio of subjects in the experimental drug group to the placebo control group is 1:1, and you will have a 50% probability of receiving JY025 combined with gefitinib or erlotinib, and a 50% probability of receiving placebo combined with gefitinib Or erlotinib.\r\nBlind people, researchers, nurses, research assistants, inspectors, applicants and blind statisticians involved in clinical trials."}],"outcomes":[{"outcome_type":"primary","measure":"Phase II ：6-month progression-free survival rate","time_frame":"6-month progression-free survival rate","description":"Progression-free survival (PFS) will statistically describe the lower quartile (Q1), median and upper quartile (Q3) and their corresponding 95% confidence intervals, and use the Kaplan-Meier method to fit Survival curve."},{"outcome_type":"primary","measure":"Phase III：BIRC-assessed at least 6 months progression-free survival (PFS)","time_frame":"BIRC-assessed at least 6 months progression-free survival (PFS)","description":"The progression-free survival ( PFS ) assessed by BIRC was statistically described by calculating the lower quartile ( Q1 ), median, upper quartile ( Q3 ) and their corresponding 95 % confidence interval. Hierarchical logrank test was used to compare the differences between groups, and Kaplan-Meier method was used to fit the survival curve. Stratified factors included EGFR mutation type ( 19del or L858R ), baseline tumor stage ( stage III or IV ), and brain metastasis ( yes or no ). HR and 95 % confidence interval were estimated by stratified COX proportional hazard model."}]}
{"nct_id":"NCT04837196","start_date":"2021-07-29","phase":"Phase 1/Phase 2","enrollment":385,"brief_title":"Study of ASP7517 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors Expressing WT1 Antigen","official_title":"A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Known to Express WT1 Antigen","primary_completion_date":"2027-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-12-31","last_update":"2021-09-21","description":"The purpose of this study is to evaluate the safety, tolerability, and clinical response of ASP7517, and determine the Recommended Phase 2 Dose (RP2D) and/or the Maximum Tolerated Dose (MTD) of ASP7517 when administered as a single agent and in combination with pembrolizumab. This study will also evaluate other measures of anticancer activity of ASP7517 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.","other_id":"7517-CL-1101","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy\r\n             that is confirmed by available pathology records or current biopsy. Participant must\r\n             also have received all standard therapies (unless the therapy is contraindicated or\r\n             intolerable) appropriate to provide clinical benefit for his/her specific tumor type.\r\n             However, participants with metastatic melanoma who have not received checkpoint\r\n             inhibitors [CPIs] (i.e., CPIs naive) may enroll in the Phase 2 Combination Therapy Arm\r\n             Dose Expansion Cohort to receive CPI: Pembrolizumab.\r\n\r\n          -  Participant must be diagnosed with solid tumor known to express WT1 antigen such as,\r\n             but not limited to melanoma, ovarian cancer or Colorectal Cancer (CRC).\r\n\r\n          -  Participant consents to provide an archival tumor specimen in a tissue block or\r\n             unstained serial slides, if available, prior to study treatment.\r\n\r\n          -  Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of \r\n             2.\r\n\r\n          -  Participant's last dose of prior antineoplastic therapy, including any immunotherapy,\r\n             was 21 days or 5 half-lives, whichever is shorter, prior to initiation of IP\r\n             administration. A participant with BRAF gene, epidermal growth factor receptor (EGFR)\r\n             or anaplastic lymphoma kinase (ALK) mutation positive non-small cell lung carcinoma is\r\n             allowed to remain on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor\r\n             (TKI) or anaplastic lymphoma kinase (ALK) or BRAF inhibitor therapy until 4 days prior\r\n             to the start of Investigational Product (IP) administration.\r\n\r\n          -  Participant has completed any radiotherapy (including stereotactic radiosurgery) at\r\n             least 2 weeks prior to IP administration.\r\n\r\n          -  Participant's Adverse Events (AEs) (excluding alopecia) from prior therapy have\r\n             improved to grade 1 or baseline within 14 days prior to start of IP.\r\n\r\n          -  Participant has adequate organ function prior to start of IP. If a participant has\r\n             received a recent blood transfusion, the laboratory tests must be obtained  4 weeks\r\n             after any blood transfusion.\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant and at least 1\r\n             of the following conditions applies:\r\n\r\n               -  Not a woman of childbearing potential (WOCBP) OR\r\n\r\n               -  WOCBP who agrees to follow the contraceptive guidance from the time of informed\r\n                  consent through at least 6 months after the final IP administration.\r\n\r\n          -  Female participant must agree not to breastfeed starting at screening and throughout\r\n             the IP and for 180 days after the final IP administration.\r\n\r\n          -  Female participant must not donate ova starting at screening and throughout the IP and\r\n             for 180 days after the final IP administration.\r\n\r\n          -  A male participant with female partner(s) of childbearing potential (including\r\n             breastfeeding partner) must agree to use contraception throughout the treatment period\r\n             and for at least 180 days after the final IP administration.\r\n\r\n          -  Male participant must not donate sperm during the treatment period and for 180 days\r\n             after the final IP administration.\r\n\r\n          -  Male participant with pregnant partner(s) must agree to remain abstinent or use a\r\n             condom for the duration of the pregnancy throughout the study period and for 180 days\r\n             after the final IP administration.\r\n\r\n          -  Participant agrees not to participate in another interventional study while receiving\r\n             IP.\r\n\r\n        Additional Inclusion Criteria for Participants in the Expansion Cohorts:\r\n\r\n          -  Participant meets one of the following:\r\n\r\n               -  Participant has the tumor type for which a confirmed response was observed in a\r\n                  monotherapy or combination therapy dose escalation (for melanoma, ovarian cancer\r\n                  and Colorectal Cancer [CRC] only) cohort; OR\r\n\r\n               -  For tumor specific expansion cohorts of ASP7517 or ASP7517 with pembrolizumab,\r\n                  participant has the applicable tumor type melanoma, ovarian cancer, CRC.\r\n\r\n          -  Participant has at least 1 measurable lesion per response evaluation criteria in solid\r\n             tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered\r\n             measurable if progression has been demonstrated in such lesions.\r\n\r\n          -  Participant consents to provide a tumor specimen in a tissue block or unstained serial\r\n             slides obtained within 56 days prior to first dose of IP. If a recent tissue sample\r\n             cannot be provided due to medical or safety concerns, enrollment into the study must\r\n             be discussed with the medical monitor.\r\n\r\n          -  Participant consents to undergoing a tumor biopsy (core tissue biopsy or excision)\r\n             during the treatment period as indicated in the schedule of assessments.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participant weighs < 45 kg at screening.\r\n\r\n          -  Participant has received investigational therapy (other than an investigational EGFR\r\n             TKI in a participant with EGFR activating mutations or ALK or BRAF inhibitor in a\r\n             participant with an ALK mutation) within 21 days or 5 half-lives, whichever is\r\n             shorter, prior to start of IP.\r\n\r\n          -  Participant requires or has received systemic steroid therapy or any other\r\n             immunosuppressive therapy within 14 days prior to Cycle 1 Day 1. Participants using a\r\n             physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30\r\n             mg per day of hydrocortisone up to 10 mg per day of prednisone) are allowed.\r\n\r\n          -  Participant has symptomatic central nervous system (CNS) metastases or participant has\r\n             evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).\r\n             Participants with previously treated CNS metastases are eligible, if they are\r\n             clinically stable and have no evidence of CNS progression by imaging for at least 4\r\n             weeks prior to start of IP and are not requiring immunosuppressive doses of systemic\r\n             steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of prednisone or\r\n             equivalent) for longer than 2 weeks.\r\n\r\n          -  Participant has an active autoimmune disease. Participants with type 1 diabetes\r\n             mellitus, endocrinopathies stably maintained on appropriate replacement therapy or\r\n             skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic\r\n             treatment are allowed.\r\n\r\n          -  Participant was discontinued from prior immunomodulatory therapy due to a grade  3\r\n             toxicity that was mechanistically related (e.g., immune related) to the agent.\r\n\r\n          -  Participant has known history of serious hypersensitivity reaction to a known\r\n             ingredient of ASP7517 or pembrolizumab or severe hypersensitivity reaction to\r\n             treatment with another monoclonal antibody.\r\n\r\n          -  Participant has a known history of human immunodeficiency virus.\r\n\r\n          -  Participant with known history of positive hepatitis B surface antigen or isolated\r\n             hepatitis B core antibody (including acute HBV or chronic HBV) or hepatitis C ([HCV]\r\n             ribonucleic acid [RNA] detected by qualitative assay). Hepatitis C RNA testing is not\r\n             required in participants with negative hepatitis C antibody testing.\r\n\r\n          -  Participant has received a live vaccine against infectious diseases within 28 days\r\n             prior to initiation of IP.\r\n\r\n          -  Participant has a history of drug-induced pneumonitis (interstitial lung disease), a\r\n             history of (non-infectious) pneumonitis that required steroids, radiation pneumonitis\r\n             or currently has pneumonitis.\r\n\r\n          -  Participant has an infection requiring systemic therapy within 14 days prior to IP.\r\n\r\n          -  Participant has received a prior allogeneic bone marrow or solid organ transplant.\r\n\r\n          -  Participant is expected to require another form of antineoplastic therapy while on IP.\r\n\r\n          -  Participant has had a myocardial infarction or unstable angina within 6 months prior\r\n             to the start of IP or currently has an uncontrolled illness including, but not limited\r\n             to symptomatic congestive heart failure, clinically significant cardiac disease,\r\n             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations\r\n             that would limit compliance with study requirements.\r\n\r\n          -  Participant has a clinically significant abnormal electrocardiogram at screening.\r\n\r\n          -  Participant has symptomatic cardiovascular disease within the preceding 12 months\r\n             unless cardiology consultation and clearance has been obtained for study\r\n             participation, including but not limited to the following: significant coronary artery\r\n             disease (e.g., requiring angioplasty or stenting), acute myocardial infarction or\r\n             unstable angina pectoris < 3 months prior screening, uncontrolled hypertension,\r\n             clinically significant arrhythmia or congestive heart failure (New York Heart\r\n             Association grade  3).\r\n\r\n          -  Any condition that makes the participant unsuitable for study participation.\r\n\r\n          -  Participant has had a major surgical procedure and has not completely recovered within\r\n             28 days prior to the start of IP.\r\n\r\n          -  Participant has a prior malignancy active (i.e., requiring treatment of intervention)\r\n             within the previous 2 years prior to the screening visit, except for locally curable\r\n             malignancies that have been apparently cured, such as basal or squamous cell skin\r\n             cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.\r\n             Participants with organ confined prostate cancer with no evidence of recurrent or\r\n             progressive disease are eligible if hormonal therapy has been initiated or the\r\n             malignancy has been surgically removed or treated with definitive radiotherapy.\r\n\r\n          -  Participant has International Normalized Ration (INR) > 1.5 x Upper Limits of Normal\r\n             (ULN) and/or activated partial thromboplastin time (aPTT) > 1.5 x institutional normal\r\n             limits.\r\n\r\n        Additional Exclusion Criteria for Participants in Combination Expansion Cohorts:\r\n\r\n          -  Participants with metastatic CRC with documented microsatellite instability-high\r\n             (MSI-H) or mismatch repair (MMR) deficient who have received prior treatment with PD-1\r\n             or programmed death-ligand (PD-L1) inhibitors such as nivolumab or pembrolizumab.\r\n\r\n          -  CPI nave metastatic melanoma participants who have received PD-1 or PD-L1 inhibitors,\r\n             such as nivolumab or pembrolizumab.\r\n\r\n          -  Participants with metastatic ovarian cancer with documented MSI-H or MMR deficient who\r\n             have received PD-1or PD-L1 inhibitors, such as nivolumab or pembrolizumab.\r\n      ","sponsor":"Astellas Pharma Global Development, Inc.","sponsor_type":"Industry","conditions":"Advanced Cancer|Advanced Malignancies","interventions":[{"intervention_type":"Drug","name":"Drug: ASP7517","description":"Intravenous (IV)"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Intravenous (IV)"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of Dose Limiting Toxicities (DLTs)","time_frame":"28 days","description":"Events below occurring within 28 days of first dose on Cycle 1 Day 1 (C1D1) and considered related to IP.\r\nMonotherapy:\r\nNon-hematologic AEs grade >= 3 not resolving to Grade <=2 within 72 hours of onset; Confirmed Hy's law; Infusion-related reaction (IRR) requiring infusion discontinuation; Treatment-related toxicity with > 2 weeks delay in initiating Cycle 2 or discontinuation during Cycle 1; Grade >= 3 anemia requiring transfusion or thrombocytopenia with bleeding requiring transfusion/hospitalization; Grade 3 febrile neutropenia with/without infection; Grade 5 treatment-related toxicity\r\nCombination Therapy:\r\nDLTs mentioned above; Grade >= 2 pneumonitis, encephalopathy, meningitis, motor/sensory neuropathy; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) in absence of liver metastases; AST or ALT > 8 x ULN in presence of liver metastases; Total bilirubin > 3 x ULN; Guillain-Barre syndrome/myasthenic syndrome/myasthenia gravis"},{"outcome_type":"primary","measure":"Number of participants with adverse events (AEs)","time_frame":"Up to 27 months","description":"An AE is any untoward medical occurrence in a participant temporally associated with the use of study IP and other study treatments, whether or not considered related to the study IP and other study treatments. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study IP and other study treatments. This includes events related to the comparator and events related to the (study) procedures. AEs will be graded using NCI-CTCAE guidelines, version 5.0."},{"outcome_type":"primary","measure":"Number of participants with serious adverse events (SAEs)","time_frame":"Up to 27 months","description":"An AE is considered \"serious\" if the event: results in death; is life threatening; requires inpatient hospitalization or leads to prolongation of hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; other medically important events."},{"outcome_type":"primary","measure":"Number of participants with laboratory value abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant laboratory values."},{"outcome_type":"primary","measure":"Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant 12-lead ECG values."},{"outcome_type":"primary","measure":"Number of participants with vital sign abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant vital sign values."},{"outcome_type":"primary","measure":"Number of participants with physical exam abnormalities and/or AEs","time_frame":"Up to 27 months","description":"Number of participants with potentially clinically significant physical exam values."},{"outcome_type":"primary","measure":"Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status","time_frame":"Up to 27 months","description":"The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance."},{"outcome_type":"primary","measure":"Objective Response Rate per modified Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR)","time_frame":"Up to 24 months","description":"iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed modified Complete Response (iCR) or modified Partial Response (iPR) per iRECIST by independent central review."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1","time_frame":"Up to 24 months","description":"ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per RECIST v1.1."},{"outcome_type":"secondary","measure":"Disease Control Rate per iRECIST (iDCR)","time_frame":"Up to 24 months","description":"iDCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR, iPR or stable disease (iSD), per iRECIST."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) per RECIST v1.1","time_frame":"Up to 24 months","description":"DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or SD per RECIST v1.1."},{"outcome_type":"secondary","measure":"Progression-Free Survival per iRECIST (iPFS) using Independent Central Review","time_frame":"Up to 24 months","description":"iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST by independent central review."},{"outcome_type":"secondary","measure":"Progression-Free Survival per iRECIST (iPFS) using Investigator Assessment","time_frame":"Up to 24 months","description":"iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST by investigator assessment."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) per RECIST v1.1 using Independent Central Review","time_frame":"Up to 24 months","description":"PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1 by independent central review."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) per RECIST v1.1 using Investigator Assessment","time_frame":"Up to 24 months","description":"PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1 by investigator assessment."},{"outcome_type":"secondary","measure":"Duration of Overall Survival (OS)","time_frame":"Up to 36 months","description":"OS is defined as the time from the date of first dose until the date of death from any cause."},{"outcome_type":"secondary","measure":"Duration of Response per iRECIST (iDOR) using Independent Central Review","time_frame":"Up to 24 months","description":"iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST by independent central review."},{"outcome_type":"secondary","measure":"Duration of Response per iRECIST (iDOR) using Investigator Assessment","time_frame":"Up to 24 months","description":"iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST by investigator assessment."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST v1.1 using Independent Central Review","time_frame":"Up to 24 months","description":"DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1 by independent central review."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST v1.1 using Investigator Assessment","time_frame":"Up to 24 months","description":"DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1 by investigator assessment."}]}
{"nct_id":"NCT04949256","start_date":"2021-07-28","phase":"Phase 3","enrollment":862,"brief_title":"Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)","official_title":"A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma","primary_completion_date":"2025-12-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-12-29","last_update":"2021-09-16","description":"The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).","other_id":"7902-014","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell\r\n             carcinoma of the esophagus\r\n\r\n          -  Male participants are abstinent from heterosexual intercourse or agree to use\r\n             contraception during the intervention period and for at least 7 days after the last\r\n             dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes\r\n             last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only\r\n             and is greater than 90 days post chemotherapy, no male contraception is needed\r\n\r\n          -  Female participant is not pregnant or breastfeeding and is not a woman of childbearing\r\n             potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective\r\n             or is abstinent from heterosexual intercourse as their preferred and usual lifestyle\r\n             during the intervention period and for at least 120 days after the last dose of\r\n             pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last\r\n             dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this\r\n             period\r\n\r\n          -  Has adequately controlled blood pressure (BP) with or without antihypertensive\r\n             medications, defined as BP150/90 millimeters of mercury (mm Hg) with no change in\r\n             antihypertensive medications within 1 week prior to randomization\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has had previous therapy for locally advanced unresectable or metastatic esophageal\r\n             cancer\r\n\r\n          -  Has locally advanced esophageal carcinoma\r\n\r\n          -  Has metastatic adenocarcinoma of the esophagus\r\n\r\n          -  Has direct invasion into adjacent organs such as the aorta or trachea\r\n\r\n          -  Has radiographic evidence of encasement of a major blood vessel, or of intratumoral\r\n             cavitation\r\n\r\n          -  Has perforation risks or significant gastrointestinal (GI) bleeding\r\n\r\n          -  Has had clinically significant hemoptysis within 3 weeks prior to the first dose of\r\n             study drug or tumor bleeding within 2 weeks prior to the first dose of study\r\n             intervention\r\n\r\n          -  Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring\r\n             frequent drainage or medical intervention\r\n\r\n          -  Has GI obstruction, poor oral intake, difficulty in taking oral medication, or\r\n             existing esophageal stent\r\n\r\n          -  Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks\r\n             prior to first dose of study interventions\r\n\r\n          -  Has received prior radiotherapy within 2 weeks of start of study intervention\r\n\r\n          -  Has received a live or live attenuated vaccine within 30 days prior to the first dose\r\n             of study intervention; administration of killed vaccines is allowed\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             or any form of immunosuppressive therapy within 7 days prior to the first dose of\r\n             study intervention, or has a history of organ transplant, including allogeneic stem\r\n             cell transplant\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years\r\n\r\n          -  Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years;\r\n             replacement therapy is not considered a form of systemic treatment and is allowed\r\n\r\n          -  Has a history of non-infectious pneumonitis/interstitial lung disease that required\r\n             steroids or current pneumonitis/interstitial lung disease\r\n\r\n          -  Has poorly controlled diarrhea\r\n\r\n          -  Has clinically significant cardiovascular disease within 12 months from first dose of\r\n             study intervention\r\n\r\n          -  Has peripheral neuropathy Grade 2\r\n\r\n          -  Has a known history of human immunodeficiency virus (HIV) infection\r\n\r\n          -  Has a known history of Hepatitis B or know active Hepatitis C virus infection\r\n\r\n          -  Has a weight loss of >20% within the last 3 months\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Metastatic Esophageal Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Levoleucovorin","description":"200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy."},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"400 mg once every 6-week-cycle, via IV infusion."},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"8 mg QD (induction) or 20 mg QD (consolidation) via oral capsule."},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy."},{"intervention_type":"Drug","name":"Drug: 5-FU","description":"4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy."},{"intervention_type":"Drug","name":"Drug: Oxaliplatin","description":"85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy."},{"intervention_type":"Drug","name":"Drug: Leucovorin","description":"400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy."}],"outcomes":[{"outcome_type":"primary","measure":"Part 1 (FP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)","time_frame":"Up to ~21 days","description":"Hematologic DLTs are defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT include any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting >3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, any grade thromboembolic event or any Grade 3 nonhematologic laboratory value requiring medical intervention or hospitalization. The number of participants in Part 1 with DLTs will be presented."},{"outcome_type":"primary","measure":"Part 1 (FP Safety Run-in): Number of Participants With Adverse Events (AEs)","time_frame":"Up to ~51 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 with AEs will be presented."},{"outcome_type":"primary","measure":"Part 1 (FP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE","time_frame":"Up to ~51 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented."},{"outcome_type":"primary","measure":"Part 2 (Main Study): Overall Survival (OS) in all Participants","time_frame":"Up to ~49 months","description":"OS is defined as the time from randomization to death due to any cause. OS in Part 2 for all randomized participants will be presented."},{"outcome_type":"primary","measure":"Part 2 (Main Study): Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in all Participants","time_frame":"Up to ~41 months","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for all randomized participants will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants","time_frame":"Up to ~34 months","description":"ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for all randomized participants will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants","time_frame":"Up to ~34 months","description":"For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for all randomized participants will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10","time_frame":"Up to ~49 months","description":"OS is defined as the time from randomization to death due to any cause. OS in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10","time_frame":"Up to ~41 months","description":"PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): ORR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10","time_frame":"Up to ~34 months","description":"ORR is defined as the percentage of participants with CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 adjusted to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by BICR. ORR in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10","time_frame":"Up to ~34 months","description":"For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), per RECIST 1.1 by BICR, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR in Part 2 for randomized participants with PD-L1 CPS ≥10 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Number of Participants With AEs","time_frame":"Up to ~49 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 with AEs will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Number of Participants who Discontinued Study Treatment Due to an AE","time_frame":"Up to ~49 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 2 who discontinue study treatment due to an AE will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Change From Baseline in Health-related Quality of life (HRQoL) Score Using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)","time_frame":"Baseline and ~24 months","description":"The EORTC QLQ-C30 is a questionnaire to assess the overall HRQoL. Participant responses to the question \" How would you rate your overall quality of life (QoL) during the past week?\" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall QoL. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL EORTC QLQ-C30 score in participants in Part 2 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)","time_frame":"Baseline and ~24 months","description":"The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants in Part 2 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): Time to Deterioration (TTD) in HRQoL Score Using EORTC QLQ-C30","time_frame":"Up to ~ 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point change from baseline in the HRQoL EORTC QLQ-C30 score. The EORTC QLQ-C30 is a questionnaire to assess the overall HRQoL. Participant responses to the question \" How would you rate your overall QoL during the past week?\" are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall QoL. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD in HRQoL EORTC QLQ-C30 score in participants in Part 2 will be presented."},{"outcome_type":"secondary","measure":"Part 2 (Main Study): TTD in HRQoL Score Using EORTC QLQ-OES18","time_frame":"Up to ~ 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point change from baseline in the HRQoL EORTC QLQ-OES18 score. The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A longer TTD indicates a better outcome. The TTD in HRQoL QLQ-OES18 score in participants in Part 2 will be presented."}]}
{"nct_id":"NCT04921358","start_date":"2021-07-27","phase":"Phase 3","enrollment":420,"brief_title":"Tislelizumab in Combination With Sitravatinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer","official_title":"A Randomized Phase 3 Study of Tislelizumab in Combination With Sitravatinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer That Progressed on or After Platinum-Based Chemotherapy and Anti-PD-(L)1 Antibody","primary_completion_date":"2024-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-06-30","last_update":"2021-08-03","description":"The purpose of this study is to evaluate the efficacy and safety of tislelizumab in combination with sitravatinib compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have disease progression following platinum-based chemotherapy and anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody, with the anti-PD-(L)1 antibody administered in combination with or following platinum-based chemotherapy.","other_id":"BGB-A317-Sitravatinib 301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          1. Metastatic or unresectable locally advanced histologically confirmed Non-Small Cell\r\n             Lung Cancer (NCSLC), not amenable to treatment with curative intent\r\n\r\n          2. Able to provide archival/fresh tumor tissues for biomarker analysis to assess PD-L1\r\n             expression and other biomarkers.\r\n\r\n          3. No known Estimated Glomerular Filtration Rate (EGFR) or BRAF mutation, or ALK\r\n             rearrangement or ROS1 rearrangement\r\n\r\n          4. Radiographic progression per Response Evaluation Criteria in Solid Tumours (RECIST)\r\n             v1.1 on or after anti-PD-(L)1 containing therapy as the most recent treatment for\r\n             locally advanced and unresectable or metastatic NSCLC.\r\n\r\n          5. At least 1 measurable lesion as defined based on RECIST v1.1 by investigator\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          1. Has received docetaxel as monotherapy or in combination with other therapies.\r\n\r\n          2. Squamous NSCLC with central cavitation, or NSCLC with hemoptysis (> 50 mL/day)\r\n\r\n          3. Participants with tumor shown by imaging to be located around important vascular\r\n             structures or if the investigator determines that the tumor is likely to invade\r\n             important blood vessels and may cause fatal bleeding.\r\n\r\n          4. Active leptomeningeal disease for metastatic NSCLC or uncontrolled, untreated brain\r\n             metastasis.\r\n\r\n          5. Active autoimmune diseases or history of autoimmune diseases that may relapse.\r\n\r\n        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer (NSCLC)","interventions":[{"intervention_type":"Drug","name":"Drug: Tislelizumab in combination with Sitravatinib","description":"Tislelizumab 200 mg intravenously once every 3 weeks in combination with sitravatinib 100 mg orally once a day, A cycle is 21 days in length  3 days, to be administered until Progressive Disease or intolerable toxicity"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Docetaxel 75 mg/m2 intravenously once every 3 weeks, A cycle is 21 days in length  3 days, to be administered until Progressive Disease or intolerable toxicity."}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival (OS)","time_frame":"From first randomization up to 35 months, approximately","description":"OS is defined as the time from first study drug administration to the date of death due to any reason."},{"outcome_type":"primary","measure":"Progression-free survival (PFS) as assessed by Independent Review Committee (IRC)","time_frame":"From first randomization up to 35 months, approximately","description":"defined as the time from randomization to the first occurrence of disease progression as determined by the IRC based on RECIST v1.1, or death from any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"From first randomization up to 35 months, approximately","description":"defined as the time from randomization to the first occurrence of disease progression as determined by the investigator based on RECIST v1.1, or death from any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"Overall response rate (ORR)","time_frame":"From first randomization up to 35 months, approximately","description":"defined as the proportion of participants with partial response or complete response as determined by the IRC based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"From first randomization up to 35 months, approximately","description":"defined as the proportion of participants whose best overall response (BOR) is complete response, partial response or stable disease as determined by the IRC based on RECIST v1.1"},{"outcome_type":"secondary","measure":"Health-related quality of life (HRQoL) as assessed according to the European Organization and Treatment of Cancer lung cancer module, QLQ-LC13","time_frame":"From first randomization up to 35 months, approximately","description":"A score of 1-4 will be administrated for each item in QLQ-LC13. The higher scores will indicate the worse outcomes."},{"outcome_type":"secondary","measure":"Health-related quality of life (HRQoL) as assessed according to the European Organization for Research and Treatment of Cancer (EORTC) core cancer (QLQ-C30)","time_frame":"From first randomization up to 35 months, approximately","description":"The EORTC QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best)."},{"outcome_type":"secondary","measure":"Health-related quality of life (HRQoL) as assessed according to the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L)","time_frame":"From first randomization up to 35 months, approximately","description":"Patient-reported outcomes based on EuroQoL-Five Dimensions, Five Levels (EQ-5D-5L) for all cohorts The EQ-5D- is a generic, self-reported measure of utility that consists of a five-item descriptive system and a visual analogue scale (EQ VAS). The descriptive system has two versions, namely the 3L and 5L, both involving five health dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). In the EQ-5D-5L that will be used, participants may choose from the following five response levels: no problems=1; slight problems=2; moderate problems=3; severe problems=4; and unable to/extreme problems=5. Higher values indicate worst health."},{"outcome_type":"secondary","measure":"Number of participants experiencing treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0","time_frame":"From first randomization up to 35 months, approximately"}]}
{"nct_id":"NCT04945421","start_date":"2021-07-23","phase":"Phase 1/Phase 2","enrollment":121,"brief_title":"IBI310 in Combination With Siltilimab in Subjects With Anti-PD-1/PD-L1 Resistance R/M NPC","official_title":"The Phase Ib/II, Open-label, Multicenter Study of IBI310 (Anti-CTLA4 mAb) in Combination With Sintilimab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma That Failed to Prior Anti-PD-1/PD-L1 Therapy","primary_completion_date":"2022-08-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-03-31","last_update":"2021-07-26","description":"This is a phase 1b/II, open label, multicenter study of IBI310 (Anti-CTLA4 mAb) in combination with Sintilimab in patients with recurrent/metastatic Nasopharyngeal Carcinoma that failed to prior Anti-PD-1/PD-L1 therapy","other_id":"CIBI310F201","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Aged 18 years;\r\n\r\n          2. ECOG 0 ~ 1;\r\n\r\n          3. Histologically/cytologically confirmed R/M NPC;\r\n\r\n          4. Failed to prior Anti-PD-1 resistance;\r\n\r\n          5. Adequate organ and bone marrow function;\r\n\r\n          6. Expected survival 12 weeks;\r\n\r\n          7. Female subjects of childbearing age or male patients whose sex partners are women of\r\n             childbearing age should take effective contraceptive measures throughout the treatment\r\n             period and within 6 months after the last administration;\r\n\r\n          8. Subjects who sign the written informed consent form, and can abide by the visits and\r\n             related procedures specified in the protocol.\r\n\r\n          9. At least 1 measurable lesion according to the Response Evaluation Criteria in Solid\r\n             Tumors Version 1.1(RECIST V1.1).\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Had tumors other than NPC within the past 5 years.\r\n\r\n          2. Had allogeneic organ or stem cell transplantation.\r\n\r\n          3. The presence of uncontrolled life-threatening illness\r\n\r\n          4. Women of child-bearing potential who are pregnant or breastfeeding because of the\r\n             potentially dangerous effects of the preparative chemotherapy on the fetus or infant.\r\n\r\n          5. Patients who have used large doses of glucocorticoids, anti-cancer monoclonal\r\n             antibodies, and other immunosuppressive agents within 4 weeks.\r\n\r\n          6. HIV positive.\r\n\r\n          7. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.\r\n\r\n          8. Severe, uncontrolled medical conditions and infections.\r\n\r\n          9. At the same time using other test drugs or in other clinical trials.\r\n\r\n         10. Refusal or inability to sign informed consent to participate in the trial.\r\n\r\n         11. Other treatment contraindications.\r\n\r\n         12. Emotional disturbance or mental illness, no civil capacity or limited capacity for\r\n             civil conduct.\r\n\r\n         13. Hepatitis B surface antigen (HBsAg) positive and HBVDNA 1000cps/ml.\r\n\r\n         14. Patients with positive HCV antibody test results can only be included in the study\r\n             when the polymerase chain reaction of HCV RNA is negative.\r\n      ","sponsor":"Innovent Biologics (Suzhou) Co. Ltd.","sponsor_type":"Industry","conditions":"NPC","interventions":[{"intervention_type":"Drug","name":"Drug: Sintilimab","description":"(IBI310 3 mg/kg IV d1, Q3W combined with sintilimab 100 mg IV d1, Q3W) or( IBI310 1 mg/kg IV d1, Q3W combined with sintilimab 200 mg IV d1, Q3W) for up to 4 cycles, and then sintilimab 200 mg IV d1, Q3W until progressive disease, intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first."},{"intervention_type":"Drug","name":"Drug: IBI310","description":"(IBI310 3 mg/kg IV d1, Q3W combined with sintilimab 100 mg IV d1, Q3W) or( IBI310 1 mg/kg IV d1, Q3W combined with sintilimab 200 mg IV d1, Q3W) for up to 4 cycles, and then sintilimab 200 mg IV d1, Q3W until progressive disease, intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first."}],"outcomes":[{"outcome_type":"primary","measure":"ORR(Objective response rate)","time_frame":"Up to 2 years","description":"Investigator evaluated ORR per RECIST V1.1"},{"outcome_type":"secondary","measure":"DOR(Duration of Response)","time_frame":"Up to 2 years","description":"defined as the time from the first documented objective response to the first documented progressive disease or death of any cause, whichever occurs first;"},{"outcome_type":"secondary","measure":"PFS (Progress Free Survival)","time_frame":"Up to 2 years","description":"defined as the time from randomization to the first documented progressive disease or death of any cause, whichever occurs first;"},{"outcome_type":"secondary","measure":"OS (Overall Survival)","time_frame":"Up to 2 years","description":"defined as the time from randomization to death of any cause in subjects without receiving any immunotherapy outside the study protocol for first-line treatment of advanced HCC;"},{"outcome_type":"secondary","measure":"DCR(Disease control rate)","time_frame":"Up to 2 years","description":"defined as the proportion of patients whose best response is CR, PR, and stable disease (SD) non-CR/non-PD"},{"outcome_type":"secondary","measure":"TTR(Time to progress)","time_frame":"Up to 2 years","description":"defined as the time from randomization to the first documented and confirmed objective response (CR or PR)"},{"outcome_type":"secondary","measure":"TEAE(Treatment Emergent Adverse Event)/SAE(Serious Adverse Event)","time_frame":"Up to 2 years","description":"Incidence and severity of treatment-emergent: which is evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v5.0, 2017) grade;"},{"outcome_type":"secondary","measure":"Changes of Quality of life, according to EORTC QLQ-C30","time_frame":"Up to 2 years","description":"According to EORTC QLQ-C30"},{"outcome_type":"secondary","measure":"Changes of Quality of life, according to EORTC QLQ-H&N35","time_frame":"Up to 2 years","description":"According to EORTC QLQ-H&N35"},{"outcome_type":"secondary","measure":"ADAs","time_frame":"Up to 2 years","description":"The immunogenicity of IBI310 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)"}]}
{"nct_id":"NCT04999605","start_date":"2021-07-22","phase":"Phase 1/Phase 2","enrollment":145,"brief_title":"A Study of AK112 Combined With PARP Inhibitor in the Treatment of Recurrent Ovarian Cancer","official_title":"Phase Ib/II Clinical Study of Anti-PD-1 and VEGF Bispecific Antibody (AK112) Combined With PARP Inhibitor in the Treatment of Recurrent Ovarian Cancer","primary_completion_date":"2023-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-06-30","last_update":"2021-08-11","description":"Phase Ib/II open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with PARP inhibitor in patients with recurrent ovarian cancer.","other_id":"AK112-204","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Be able and willing to provide written informed consent.\r\n\r\n          -   18 years old to  75 years old at study enrollment, female subjects.\r\n\r\n          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Have a life expectancy of at least 3 months.\r\n\r\n          -  Have histologically or cytologically diagnosis of epithelial ovarian, fallopian tube,\r\n             or primary peritoneal carcinoma.\r\n\r\n          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\r\n             v1.1 assessed by investigator.\r\n\r\n          -  Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.\r\n\r\n          -  Has adequate organ function.\r\n\r\n          -  All subjects of reproductive potential must agree to use an effective method of\r\n             contraception, as determined by the Investigator, during and for 120 days after the\r\n             last dose of study treatment.\r\n\r\n          -  Able to to comply with all requirements of study participation (including all study\r\n             procedures).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previous history (within five years) or concurrent malignant neoplasm, except that\r\n             basal cell carcinoma and/or squamous cell carcinoma of the skin, superficial bladder\r\n             cancer, cervical cancer in situ or breast cancer in situ that has undergone curative\r\n             therapy.\r\n\r\n          -  Participation in a study of an investigational drug or using an investigational device\r\n             within 4 weeks of first study drug administration.\r\n\r\n          -  Previous use of PARP inhibitors.\r\n\r\n          -  Ovarian, fallopian tube or primary peritoneal cancer cancer of non-epithelial origin\r\n             (such as germ cell carcinoma).\r\n\r\n          -  Previous targeted therapy using small molecule and/or anti-angiogenic therapy\r\n             (including but not limited to bevacizumab or its biosimilar).\r\n\r\n          -  Have a potent or moderate CYP3A inhibitor, or a potent or moderate CYP3A inducer\r\n             within 1 week prior to first study drug administration (or 5 drug half-lives,\r\n             whichever is longer).\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in the past 2\r\n             years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive\r\n             drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid\r\n             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a\r\n             form of systemic treatment.\r\n\r\n          -  Active or previous history of inflammatory bowel disease such as Crohn's disease,\r\n             ulcerative colitis or chronic diarrhea.\r\n\r\n          -  History of immunodeficiency and/or HIV antibody positive subjects.\r\n\r\n          -  Has severe infection 4 weeks prior to first study drug administration, including but\r\n             not limited to complications requiring hospitalization, sepsis or severe pneumonia;\r\n             active infection requiring systemic anti-infective therapy within 2 weeks prior to\r\n             first study drug administration (excluding antiviral therapy for hepatitis B or C).\r\n\r\n          -  Has known active Hepatitis B that is untreated and requiring antiviral therapy during\r\n             study period; or active Hepatitis C subjects (HCV antibody positive with HCV-RNA\r\n             levels above the detection threshold).\r\n\r\n          -  Has undergone major surgery or severe trauma within 30 days prior to the first study\r\n             drug administration.\r\n\r\n          -  Has known active central nervous system (CNS) metastases.\r\n\r\n          -  Uncontrolled co-morbidities including but not limited to symptomatic congestive heart\r\n             failure (NYHA2), unstable angina, acute myocardial infarction, poorly controlled\r\n             arrhythmias, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic\r\n             disorders, severe peptic ulcer disease or gastritis.\r\n\r\n          -  Uncontrolled hypertension despite optimal medical treatment; history of hypertensive\r\n             crisis or hypertensive encephalopathy.\r\n\r\n          -  Any arterial thromboembolism, transient ischemic attack, cerebrovascular accident\r\n             occurred within 6 months prior to the first study drug administration.\r\n\r\n          -  History of abdominal fistula or gastrointestinal perforation associated with anti-VEGF\r\n             therapy; imaging results revealed invasion of the intestinal wall by tumor during\r\n             screening.\r\n\r\n          -  Imaging or clinical findings of gastrointestinal obstruction, including incomplete\r\n             obstruction.\r\n\r\n          -  Unable to swallow tablets or has had gastrointestinal abnormalities that may affect\r\n             drug absorption as determined by the investigator.\r\n\r\n          -  Has had live vaccine within 30 days prior to first study drug administration or plan\r\n             to receive live vaccine during the study period.\r\n\r\n          -  Has known psychiatric or substance abuse disorders, including alcohol or drug abuse.\r\n\r\n          -  Pregnant or lactating female subject.\r\n\r\n          -  Any prior or concurrent disease, treatment, or laboratory test abnormality that may\r\n             confuse study results, affect subjects' full participation in the study, or may not be\r\n             in their best interest to participate.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"Ovarian Neoplasms|Recurrent Ovarian Carcinoma|Relapsed Ovarian Cancer|Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AK112 low dose","description":"AK112 injection low dose+ olaparib (Lynparza) PARP inhibitor"},{"intervention_type":"Drug","name":"Drug: AK112 medium dose","description":"AK112 injection medium dose+ olaparib (Lynparza) PARP inhibitor"},{"intervention_type":"Drug","name":"Drug: AK112 high dose","description":"AK112 injection high dose+ olaparib (Lynparza) PARP inhibitor"}],"outcomes":[{"outcome_type":"primary","measure":"Safety endpoint: number of subjects with adverse events (AE)","time_frame":"Up to approximately 2 years","description":"An AE is any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment."},{"outcome_type":"primary","measure":"Primary efficacy endpoint: objective response rate (ORR)","time_frame":"Up to approximately 2 years","description":"ORR is the proportion of subjects with complete response(CR) or partial response(PR) assessed according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Efficacy Endpoint assessed according to RECIST v1.1 : disease control rate (DCR)","time_frame":"Up to approximately 2 years","description":"DCR based on RECIST v1.1. DCR is defined as the proportion of subjects with CR, PR, or SD."},{"outcome_type":"secondary","measure":"Efficacy Endpoint assessed according to RECIST v1.1 : progression-free survival (PFS)","time_frame":"Up to approximately 2 years","description":"PFS based on RECIST v1.1. PFS is defined as the time from the date of randomization till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first)"},{"outcome_type":"secondary","measure":"Efficacy Endpoint assessed according to RECIST v1.1 : Overall survival (OS)","time_frame":"Up to approximately 2 years","description":"OS based on RECIST v1.1. OS is defined as the time from the date of randomization or first dosing date to death due to any cause"},{"outcome_type":"secondary","measure":"Serum PK concentrations of AK112","time_frame":"Up to approximately 2 years","description":"Serum PK concentrations of AK112 in individual subjects at different time points after AK112 administration"},{"outcome_type":"secondary","measure":"To evaluate the immunogenicity of AK112: Number of subjects with anti-drug antibodies (ADA)","time_frame":"Up to approximately 2 years","description":"Immunogenicity of AK112: Number of subjects with detectable anti-drug antibodies (ADA)"},{"outcome_type":"secondary","measure":"To evaluate the immunogenicity of AK112: Percentage of subjects with anti-drug antibodies (ADA)","time_frame":"Up to approximately 2 years","description":"Immunogenicity of AK112: Percentage of subjects with detectable anti-drug antibodies (ADA)"},{"outcome_type":"secondary","measure":"To evaluate the correlation between the expression of PD-L1 and the antitumor activity of AK112 in tumor tissues","time_frame":"Up to approximately 2 years","description":"Correlation between PD-L1 and AK112 in tumor tissues"},{"outcome_type":"secondary","measure":"To evaluate the association between gBRCA1/2 mutation in peripheral blood and the antitumor activity of AK112 in subjects with recurrent ovarian cancer","time_frame":"Up to approximately 2 years","description":"Association between gBRCA1/2 mutation in peripheral blood and antitumor activity of AK112"}]}
{"nct_id":"NCT04956640","start_date":"2021-07-19","phase":"Phase 1","enrollment":260,"brief_title":"Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)","official_title":"A Phase 1a/1b Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors","primary_completion_date":"2023-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-10-31","last_update":"2021-09-21","description":"The purpose of this study is to find out whether the study drug, LY3537982, is safe and effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must have already received or were not able to tolerate the standard of care. The study will last up to approximately 2 years.","other_id":"LOXO-RAS-20001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients have measurable disease per Response Evaluation Criteria in Solid Tumors\r\n             version 1.1 (RECIST v1.1).\r\n\r\n          -  Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or\r\n             circulating tumor deoxyribonucleic acid (DNA).\r\n\r\n          -  Participants must have a histological or a cytologically proven diagnosis of locally\r\n             advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.\r\n\r\n          -  Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\r\n\r\n          -  Have adequate organ function.\r\n\r\n          -  Have discontinued all previous treatments for cancer with resolution of any\r\n             significant ongoing adverse events (AEs).\r\n\r\n          -  Must be able to swallow capsule/tablet.\r\n\r\n          -  Agree and adhere to contraceptive use, if applicable.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Disease suitable for local therapy administered with curative intent.\r\n\r\n          -  Have an active, ongoing, or untreated infection.\r\n\r\n          -  Have a serious pre-existing medical condition(s) that, in the judgment of the\r\n             investigator, would preclude participation in this study.\r\n\r\n          -  Have a serious cardiac condition.\r\n\r\n          -  Have a second active primary malignancy or have been diagnosed and/or treated for an\r\n             additional malignancy within 3 years prior to enrollment.\r\n\r\n          -  Have symptomatic central nervous system (CNS) malignancy or metastasis and/or\r\n             carcinomatous meningitis. Patients with treated CNS metastases are eligible for this\r\n             study if they are not currently receiving corticosteroids in excess of 10 milligrams\r\n             (mg) per day prednisone/prednisolone (or equivalent) and their disease is asymptomatic\r\n             and radiographically stable for at least 30 days.\r\n\r\n          -  Have received prior treatment with any KRAS G12C small molecule inhibitor, except in\r\n             certain scenarios where such prior therapy is allowed as per protocol.\r\n\r\n          -  For Cohorts B2, B3, and B5/C1, patients treated with drugs known to be strong\r\n             inhibitors or inducers of cytochrome P450 (CYP)3A.\r\n\r\n          -  The following patients will be excluded from Cohort B4:\r\n\r\n               -  Experienced certain serious side effects with prior immunotherapy.\r\n\r\n               -  Have an active autoimmune disease that has required systemic anti-autoimmune\r\n                  treatment in the past 2 years.\r\n\r\n               -  Have undergone prior allogeneic hematopoietic stem cell transplantation within\r\n                  the last 5 years.\r\n\r\n               -  Have received a live vaccine within 30 days prior to the first dose of study\r\n                  drug.\r\n\r\n          -  Pregnant, breastfeeding, or expecting to conceive or father children within the\r\n             projected duration of the trial through 180 days after the last dose of study\r\n             medication.\r\n\r\n          -  Known allergic reaction against any of the components of the study treatments.\r\n      ","sponsor":"Eli Lilly and Company","sponsor_type":"Industry","conditions":"Pancreatic Neoplasms|Ovarian Neoplasms|Endometrial Neoplasms|Colorectal Neoplams|Carcinoma, Non-Small-Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: LY3537982","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Abemaciclib","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Erlotinib","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Sintilimab","description":"Intravenous"},{"intervention_type":"Drug","name":"Drug: Temuterkib","description":"Oral"},{"intervention_type":"Drug","name":"Drug: LY3295668","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Cetuximab","description":"Intravenous"}],"outcomes":[{"outcome_type":"primary","measure":"Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy","time_frame":"Cycle 1 (21 Days)","description":"Measured by the number of patients with dose-limiting toxicities (DLTs)"},{"outcome_type":"primary","measure":"Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents","time_frame":"Cycle 1 (21 Days)","description":"Measured by the number of patients with dose-limiting toxicities (DLTs)"},{"outcome_type":"secondary","measure":"To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)","time_frame":"Estimated up to 2 years","description":"ORR"},{"outcome_type":"secondary","measure":"To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)","time_frame":"Estimated up to 2 years","description":"DOR"},{"outcome_type":"secondary","measure":"To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)","time_frame":"Estimated up to 2 years","description":"TTR"},{"outcome_type":"secondary","measure":"To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)","time_frame":"Estimated up to 2 years","description":"DCR"},{"outcome_type":"secondary","measure":"To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)","time_frame":"Estimated up to 2 years","description":"PFS"},{"outcome_type":"secondary","measure":"To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)","time_frame":"Estimated up to 2 years","description":"OS"},{"outcome_type":"secondary","measure":"To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)","time_frame":"Predose estimated up to 2 years","description":"PK: AUC of LY3537982"},{"outcome_type":"secondary","measure":"To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)","time_frame":"Predose estimated up to 2 years","description":"PK: Cmax of LY3537982"}]}
{"nct_id":"NCT04952597","start_date":"2021-07-15","phase":"Phase 2","enrollment":120,"brief_title":"Study of Ociperlimab Plus Tislelizumab Plus Chemoradiotherapy in Participants With Untreated Limited-Stage Small Cell Lung Cancer","official_title":"A Phase 2, Multicenter, Randomized, 3-Arm, Open-Label Study to Investigate the Preliminary Efficacy and Safety of the Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) Plus Tislelizumab Plus Concurrent Chemoradiotherapy in Patients With Untreated Limited-Stage Small Cell Lung Cancer","primary_completion_date":"2024-03-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-03-30","last_update":"2021-07-30","description":"This phase 2 trial examining the combination of ociperlimab plus tislelizumab plus cCRT is expected to provide valuable data to advance treatment options in the serious unmet medical need population of LS-SCLC patients. Immunotherapy combined with chemoradiotherapy may have a synergetic anti -cancer activities. The combination of anti-TIGIT antibody and anti-PD-1/L1 antibody may augment the immune effect with tolerable safety profile. The novel therapeutic strategy with dule immune therapy in combination with CRT is expected to provide valuable data to advance treatment options in the population of LS-SCLC patients.","other_id":"AdvanTIG-204","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Patient has pathologically (histologically or cytologically) proven diagnosis of small\r\n             cell lung cancer\r\n\r\n          -  Has limited-stage disease (stage Tx, T1-T4, N0-3, M0; AJCC staging, 8th edition), and\r\n             can be safely treated with definitive radiation doses.\r\n\r\n          -  Patient has not received any prior treatment for LS-SCLC.\r\n\r\n          -  Patient has measurable disease as assessed according to RECIST v1.1 that is\r\n             appropriate for selection as a target lesion for repeat measurement, as determined by\r\n             local site investigator/radiology review\r\n\r\n          -  ECOG Performance Status  2 assessed within 7 days before the first administration of\r\n             study intervention, and must have a life expectancy of  12 weeks.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Mixed small cell lung cancer histology. Note: mixed SCLC with the component of\r\n             neuroendocrine carcinoma origin is considered eligible\r\n\r\n          -  Have received surgical resection for LS-SCLC\r\n\r\n          -  Any patient for whom the tumor is considered resectable by surgery or stereotactic\r\n             body radiation therapy/stereotactic ablative radiotherapy should be considered\r\n             ineligible\r\n\r\n          -  Is expected to require any other form of antineoplastic therapy while on study.\r\n\r\n          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, or any other\r\n             antibody or drug specifically targeting T-cell costimulation or checkpoint pathways\r\n\r\n        Note: Other protocol-defined Inclusion/Exclusion criteria may appl\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Limited Stage Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Ociperlimab","description":"Ociperlimab is a monoclonal antibody formulated for intravenous injection."},{"intervention_type":"Drug","name":"Drug: Tislelizumab","description":"Tislelizumab is a monoclonal antibody formulated for intravenous injection."},{"intervention_type":"Drug","name":"Drug: Concurrent Chemoradiotherapy","description":"Management (handling, storage, administration, and disposal) of cisplatin, carboplatin, and etoposide will be in accordance with the relevant local guidelines and/or prescribing information/summary of product characteristics."}],"outcomes":[{"outcome_type":"primary","measure":"Progression free survival (PFS)","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."},{"outcome_type":"secondary","measure":"Complete Response (CR) rate as assessed by investigator per RECIST v1.1","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR)","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."},{"outcome_type":"secondary","measure":"Safety and tolerability: The incidence and severity of treatment-emergent adverse events (TEAEs)","time_frame":"30 months from First Patient In date","description":"graded according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)."},{"outcome_type":"secondary","measure":"Distant metastasis-free survival (DMFS)","time_frame":"30 months from First Patient In date","description":"Determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1."}]}
{"nct_id":"NCT04951648","start_date":"2021-07-15","phase":"Phase 3","enrollment":220,"brief_title":"A Phase III Study to Assess the Efficacy and Safety of Almonertinib Versus Platinum-based Chemotherapy as First-line Therapy in Patients With Locally Advanced or Metastatic NSCLC Harbouring Uncommon EGFR Mutation","official_title":"A Randomized Controlled, Open-lable, Phase III, Multicenter Clinical Study of Almonertinib Versus Platinum-based Chemotherapy as First-line Therapy in Patients With Locally Advanced or Metastatic NSCLC Harbouring Uncommon EGFR Mutation","primary_completion_date":"2023-10-04","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-09-06","last_update":"2021-07-07","description":"To assess the efficacy and safety of Almonertinib versus platinum-based chemotherapy as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutation.","other_id":"HS-10296-305","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Subjects are willing to participate in this clinical study, understand the study\r\n             procedures and are able to sign the informed consent in person.\r\n\r\n          2. Age at least 18 years.\r\n\r\n          3. Histologically or cytologically confirmed diagnosis of primary non-small lung cancer\r\n             (NSCLC), histologically confirmed non-squamous pathology.\r\n\r\n          4. Locally advanced or metastatic NSCLC.\r\n\r\n          5. Patients must be treatment-nave for locally advanced or metastatic NSCLC.\r\n\r\n          6. The tumor harbors uncommon EGFR mutations (one of the following EGFR mutation: L861Q,\r\n             G719X or S768I), assessed by Xiamen AmoyDx EGFR (ADx-ARMS, Super-ARMS method) kit in\r\n             central laboratory.\r\n\r\n          7. Measurable disease by RECIST 1.1.\r\n\r\n          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          9. Female patients should be using adequate contraceptive measures and should not be\r\n             breastfeeding during the study and six months after the last dosing of study. Male\r\n             patients should be willing to use barrier contraception (condoms) during the study and\r\n             six months after the last dosing of study.\r\n\r\n         10. A pregnancy test should be done before randomization unless having an evidence of\r\n             non-child-bearing potential.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Treatment with any of the following:\r\n\r\n               1. Prior treatment with EGFR-TKI therapy.\r\n\r\n               2. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field\r\n                  of radiation within 4 weeks prior to randomization.\r\n\r\n               3. The presence of pleural effusion/peritoneal effusion/pericardial effusion\r\n                  requiring clinical intervention.\r\n\r\n               4. Major surgery within 4 weeks prior to randomization.\r\n\r\n               5. Spinal cord compression or unstable brain metastasis; Meningeal or brainstem\r\n                  metastases.\r\n\r\n               6. Patients had received medications or herbal supplements known to be strong\r\n                  inducers and inhibitors of cytochrome CYP3A4 within 7 days prior to randomization\r\n                  or required to continue these agents during the study period.\r\n\r\n               7. Patients are receiving medications known to prolong QT interval or may cause tip\r\n                  torsion ventricular tachycardia, or are still in the washout period (relatively\r\n                  random phase), or need to be continued during the study period.\r\n\r\n               8. Patients were subjects in another clinical trial within 4 weeks prior to\r\n                  randomization or patients were within 5 half-lives of any other investigational\r\n                  agent.\r\n\r\n          2. Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE)  Grade\r\n             2 from the prior anticancer therapy.\r\n\r\n          3. Inadequate bone marrow reserve or organ function.\r\n\r\n          4. Any of the following cardiac criteria:\r\n\r\n               1. Mean resting corrected QT interval (QTc) > 470 ms obtained from 3\r\n                  electrocardiograms (ECGs), using the screening clinic's ECG machine and\r\n                  Fridericia's formula for QT interval correction (QTcF).\r\n\r\n               2. Any clinically important abnormalities in rhythm, conduction, or morphology of\r\n                  the resting ECG (e.g., PR interval > 250 ms).\r\n\r\n               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic\r\n                  events, such as heart failure or any concomitant medication known to prolong the\r\n                  QT interval.\r\n\r\n               4. Left ventricular ejection fraction (LVEF) <50%.\r\n\r\n          5. History of other malignancies, excluding fully treated non-melanoma skin cancer,\r\n             Malignant freckled nevus, in-situ cancer, other solid tumors that hadn't been\r\n             recurrent for > 5 years following the end of treatment, or local prostate cancer after\r\n             radical resection.\r\n\r\n          6. Any evidence of severe or uncontrolled systemic diseases (including uncontrolled\r\n             hypertension and active bleeding diatheses) or active infection (including hepatitis\r\n             B, hepatitis C, and human immunodeficiency virus (HIV), etc.).\r\n\r\n          7. Acquired or congenital immune deficiency diseases, or history of organ\r\n             transplantation.\r\n\r\n          8. Serious gastrointestinal function abnormalities that may interfere with drug\r\n             ingestion, transport, or absorption.\r\n\r\n          9. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion,\r\n             present a specific risk to the patient's safety.\r\n\r\n         10. Pregnant or lactating, or intending to become pregnant during the study\r\n\r\n         11. Judgment by the investigator that the patient should not participate in the study if\r\n             the patient is unlikely to comply with study procedures, restrictions, and\r\n             requirements.\r\n\r\n         12. Any disease or condition that, in the opinion of the investigator, would compromise\r\n             the safety of the patient or interfere with study assessments.\r\n      ","sponsor":"Jiangsu Hansoh Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Almonertinib","description":"Almonertinib 165 mgorally once a day Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met."},{"intervention_type":"Drug","name":"Drug: chemotherapy","description":"Pemetrexed (500mg/m2) plus Carboplatin (AUC5)or Pemetrexed (500mg/m2) plus Cisplatin (75mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4~6 cycles, followed by pemetrexed mainten-ance therapy every 3 weeks until disease progress-ssion, unacceptable toxicity or other discontinuation criteria are met."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) assessed by IRC (Independent Review Committee)","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.","description":"PFS is defined as the time from randomization until the date of objective disease progression or death regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"PFS assessed by INVs (Investigators)","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.","description":"PFS is defined as the time from randomization until the date of disease progression as assessed by INVs according to RECIST 1.1 or death from any cause on study."},{"outcome_type":"secondary","measure":"Objective response rate (ORR) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.","description":"ORR is defined as the number (%) of patients with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of response (DoR) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.","description":"DoR is defined as the time from date for first documented response of until the documented response of progression per RECIST 1.1 or death in the absence of progression based on blinded independent central review assessment."},{"outcome_type":"secondary","measure":"Disease control rate (DCR) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 2 years.","description":"DCR is defined as the percentage of patients who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Depth of response (DepOR) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.","description":"DepOR is defined as the change amount of the sum of the lengths of the longest diameters of the target lesions on blinded independent central review assessment according to RECIST 1.1 in the absence of New Lesions (NLs) or progression of Non-Target Lesions when compared to baseline."},{"outcome_type":"secondary","measure":"Proportion of patients alive and progression free at 6 months (APF6) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 6 months post-randomization.","description":"APF6 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 6 months after randomization."},{"outcome_type":"secondary","measure":"Proportion of patients alive and progression free at 9 months (APF9) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 9 months post-randomization.","description":"APF9 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 9 months after randomization."},{"outcome_type":"secondary","measure":"Proportion of patients alive and progression free at 12 months (APF12) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 12 months post-randomization.","description":"APF12 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization."},{"outcome_type":"secondary","measure":"Proportion of patients alive and progression free at 24 months (APF24) assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~6 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 24 months post-randomization.","description":"APF24 is defined as the percentage (%) of patients who were alive and progression free per RECIST 1.1 at 24 months after randomization."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From the date of randomization until death due to any cause; up to a maximum of approximately 3 years.","description":"OS is defined as the time from the date of randomization until death due to any cause."},{"outcome_type":"secondary","measure":"Percentage of patients alive at 36 months (OS36)","time_frame":"From randomization until death due to any cause, up to a maximum of approximately 3 years.","description":"OS36 was defined as the percentage (%) of patients who were alive at 36 months after randomization per the Kaplan-Meier estimate of OS at 36 months."},{"outcome_type":"secondary","measure":"Incidence of Adverse Events (AEs)","time_frame":"From the screening period to 28 days after treatment completion, approximately 3 years.","description":"AEs are graded according to CTCAE v5.0 and recorded in the case report form."}]}
{"nct_id":"NCT04951635","start_date":"2021-07-15","phase":"Phase 3","enrollment":150,"brief_title":"A Phase III Study to Assess the Effects of Almonertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer","official_title":"A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre Study of Almonertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based Chemoradiation Therapy","primary_completion_date":"2024-07-15","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2027-01-15","last_update":"2021-07-07","description":"To assess the efficacy and safety of Almonertinib versus placebo following chemoradiation in patients with stage III unresectable epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC).","other_id":"HS-10296-304","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Provision of informed consent before any study-specific procedures, sampling and\r\n             analyses.\r\n\r\n          2. Male or female, age at least 18 years.\r\n\r\n          3. Histologically or cytologically confirmed diagnosis of primary non-small lung cancer\r\n             (NSCLC) on predominantly non-squamous pathology who present with locally advanced,\r\n             unresectable (Stage III) disease (according to AJCC 8th edition lung cancer\r\n             classification). Recommended by not required: In addition to obvious cT4 disease,\r\n             lymph node status N2 or N3 should be confirmed by intrabronchial ultrasound,\r\n             mediastinoscopy or thoracoscopy biopsy, and under the condition of no biopsy or\r\n             negative biopsy, the whole body screening of 18F-Fluro-deoxyglucose positron emission\r\n             tomography (PET)or contrast agent-enhanced computed tomography (CT) to confirm.\r\n\r\n          4. The tumor harbours one of the two common EGFR mutations known to be associated with\r\n             EGFR-TKI sensitivity (Ex19Del, L858R), either alone or in combination with other EGFR\r\n             mutations including T790M, assessed by cobas EGFR Mutation Test (Roche Diagnostics)\r\n             or Xiamen AmoyDx EGFR (ADx-ARMS, Super-ARMS method) kit in site or central laboratory.\r\n\r\n          5. Patients must have received either concurrent chemoradiation or sequential\r\n             chemoradiation including at least 2 cycles of platinum based chemotherapy and a total\r\n             dose of radiation of 60 Gy 10% (54 to 66 Gy).\r\n\r\n          6. Chemoradiation must be completed 6 weeks prior to randomization.\r\n\r\n          7. Patients must not have had disease progression during or following definitive\r\n             platinum-based, chemoradiation therapy.\r\n\r\n          8. A WHO performance status of 0-1 with no deterioration over the past 2 weeks and a\r\n             minimum life expectancy of 12 weeks.\r\n\r\n          9. Female patients should be using adequate contraceptive measures and should not be\r\n             breastfeeding at the screening period, during the study, and six months after the last\r\n             dosing of study. A pregnancy test should be done before first dosing unless having\r\n             evidence of non-child-bearing potential.\r\n\r\n         10. Male patients should be willing to use barrier contraception (condoms)\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Treatment with any of the following:\r\n\r\n               1. Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or\r\n                  investigational agents for NSCLC outside of that received in the definitive\r\n                  setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT\r\n                  regimens is allowed for treatment of Stage III disease). Patients who have\r\n                  previously undergone surgery for stage I or stage II NSCLC can be enrolled. If\r\n                  neoadjuvant or adjuvant therapy (non-EGFR tyrosine kinase inhibitor) is used,\r\n                  neoadjuvant or adjuvant therapy needs to be completed for at least half a year (6\r\n                  months) before enrollment.\r\n\r\n               2. Prior treatment with EGFR-TKI therapy.\r\n\r\n               3. Major surgery (including primary tumor surgery, excluding placement of vascular\r\n                  access) within 4 weeks of the first dose of study drug.\r\n\r\n               4. Patients currently receiving (unable to stop use prior to receiving the first\r\n                  dose of study treatment) medications or herbal supplements known to be strong\r\n                  inducers and inhibitors of cytochrome CYP3A4 (at least 7 days prior to receiving\r\n                  the first dose of study drug).\r\n\r\n               5. Treatment with an investigational drug within five half-lives of the compound or\r\n                  any of its related material.\r\n\r\n          2. Mixed small cell and non-small cell lung cancer histology.\r\n\r\n          3. History of interstitial lung disease (ILD) prior to chemoradiation.\r\n\r\n          4. Symptomatic pneumonitis following chemoradiation.\r\n\r\n          5. Inadequate bone marrow reserve or organ function.\r\n\r\n          6. Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE)  Grade\r\n             2 from the prior chemoradiation therapy.\r\n\r\n          7. Any of the following cardiac criteria:\r\n\r\n               1. Mean resting corrected QT interval (QTc) > 470 ms obtained from 3\r\n                  electrocardiograms (ECGs), using the screening clinic's ECG machine and\r\n                  Fridericia's formula for QT interval correction (QTcF).\r\n\r\n               2. Any clinically important abnormalities in rhythm, conduction, or morphology of\r\n                  the resting ECG (e.g., PR interval > 250 ms).\r\n\r\n               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic\r\n                  events, such as heart failure or any concomitant medication known to prolong the\r\n                  QT interval.\r\n\r\n               4. Left ventricular ejection fraction (LVEF)  40%.\r\n\r\n          8. History of other malignancies, excluding fully treated non-melanoma skin cancer,\r\n             in-situ cancer, or other solid tumors that hadn't recurrent for > 5 years following\r\n             the end of treatment.\r\n\r\n          9. Any evidence of severe or uncontrolled systemic diseases (including uncontrolled\r\n             hypertension and active bleeding diatheses) or active infection (including hepatitis\r\n             B, hepatitis C, and human immunodeficiency virus (HIV)).\r\n\r\n         10. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to\r\n             swallow the study drug that would preclude adequate absorption of Almonertinib.\r\n\r\n         11. History of hypersensitivity to any active or inactive ingredient of Almonertinib or to\r\n             drugs with a similar chemical structure or class to Almonertinib.\r\n\r\n         12. Judgment by the investigator that the patient should not participate in the study if\r\n             the patient is unlikely to comply with study procedures, restrictions, and\r\n             requirements.\r\n\r\n         13. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion,\r\n             present a specific risk to the patient's safety.\r\n\r\n         14. Any disease or condition that, in the opinion of the investigator, would compromise\r\n             the safety of the patient or interfere with study assessments.\r\n      ","sponsor":"Jiangsu Hansoh Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Almonertinib","description":"The initial dose of Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions.\r\nTreatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo)."},{"intervention_type":"Drug","name":"Drug: Placebo Almonertinib","description":"The initial dose of Placebo Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions.\r\nTreatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. The 2:1 ratio (Almonertinib to placebo)."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) assessed by IRC (Independent Review Committee)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.","description":"Progression-free survival (PFS) assessed by IRC (Independent Review Committee) Description: PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"PFS assessed by INVs (Investigators)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.","description":"PFS is defined as the time from randomization to progression of tumor as assessed by INVs or death from any cause on study."},{"outcome_type":"secondary","measure":"Time to CNS PFS assessed by IRC","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years.","description":"Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From baseline until death due to any cause; up to a maximum of approximately 4 years.","description":"OS is defined as the time from the date of randomization until death due to any cause."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.","description":"Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.","description":"Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.","description":"Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Time to death or distant metastases (TTDM)","time_frame":"Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years.","description":"Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Incidence of Adverse Events (AEs)","time_frame":"From the screening period to 28 days after treatment completion, approximately 4 years.","description":"AEs are graded according to CTCAE v5.0 and recorded in the case report form."}]}
{"nct_id":"NCT04924101","start_date":"2021-07-15","phase":"Phase 2","enrollment":120,"brief_title":"Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Chemotherapy as First-Line Treatment in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (MK-3475-B99/ KEYNOTE-B99)","official_title":"A Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Etoposide and Cisplatin or Carboplatin for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYNOTE-B99)","primary_completion_date":"2026-07-14","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-07-14","last_update":"2021-09-16","description":"The purpose of this study is to evaluate the use of investigational agents (MK-4830, MK-5890 and Lenvatinib (MK-7902)) in combination with pembrolizumab and etoposide/platinum chemotherapy for the first-line treatment of participants with extensive-stage small cell Lung Cancer (ES-SCLC). No formal hypothesis testing will be performed for this study.","other_id":"3475-B99","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has histologically or cytologically confirmed diagnosis of extensive-stage small cell\r\n             lung cancer (ES-SCLC) in need of first-line therapy\r\n\r\n          -  Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint\r\n             Committee on Cancer, Eighth Edition\r\n\r\n          -  Male participants are eligible to participate if they agree to the following during\r\n             the intervention period and for at least the time needed to eliminate each study\r\n             intervention after the last dose of study intervention. The length of time required to\r\n             continue contraception for each study intervention is as follows: Lenvatinib (7 days);\r\n             Etoposide, Cisplatin, or Carboplatin (180 days) and Pembrolizumab, MK-4830, or MK-5890\r\n             (no contraception measures); refrain from donating sperm plus either be abstinent from\r\n             heterosexual intercourse as their preferred and usual lifestyle (abstinent on a\r\n             long-term and persistent basis) and agree to remain abstinent or must agree to use\r\n             contraception per protocol unless confirmed to be azoospermic\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant or\r\n             breastfeeding, and at least one of the following conditions applies: Is not a\r\n             woman/women of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive\r\n             method that is highly effective with low user dependency or be abstinent from\r\n             heterosexual intercourse as their preferred and usual lifestyle (abstinent on a\r\n             long-term and persistent basis), during the intervention period and for at least the\r\n             time needed to eliminate each study intervention after the last dose of study\r\n             intervention and agrees not to donate eggs to others or freeze/store for her own use\r\n             for the purpose of reproduction during this period. The length of time required to\r\n             continue contraception for each study intervention is as follows: Lenvatinib (30\r\n             days), Etoposide, Cisplatin, or Carboplatin (180 days), and Pembrolizumab, MK-4830, or\r\n             MK-5890 (120 days)\r\n\r\n          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as\r\n             required by local regulations) within 24 hours before the first dose of study\r\n             intervention\r\n\r\n          -  Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology\r\n             and verified by blinded independent central review (BICR)\r\n\r\n          -  Submits an archival tumor tissue sample or newly obtained core, incisional, or\r\n             excisional biopsy of a tumor lesion not previously irradiated where such sample exist\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed\r\n             within 7 days before randomization\r\n\r\n          -  Has adequate organ function within 10 days before the first dose of study intervention\r\n\r\n          -  Has adequately controlled blood pressure (BP) with or without antihypertensive\r\n             medications, defined as BP 150/90 mm Hg with no changes in antihypertensive\r\n             medications within 1 week before randomization\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has had major surgery within 3 weeks before first dose of study interventions\r\n\r\n          -  Has a preexisting Grade 3 gastrointestinal or non-gastrointestinal fistula\r\n\r\n          -  Has urine protein 1 g/24 hours\r\n\r\n          -  Has a left ventricular ejection fraction (LVEF) below the institutional (or local\r\n             laboratory) normal range, as determined by multiple gated acquisition (MUGA) or\r\n             echocardiogram (ECHO)\r\n\r\n          -  Prolongation of QT interval with Fridericia's correction (QTcF) interval to >480 ms\r\n\r\n          -  Has clinically significant cardiovascular disease or major arterial thromboembolic\r\n             event within 12 months before first dose of study intervention, including New York\r\n             Heart Association Class III or IV congestive heart failure, unstable angina,\r\n             myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated\r\n             with hemodynamic instability\r\n\r\n          -  Has active hemoptysis within 3 weeks before the first dose of study intervention\r\n\r\n          -  Has gastrointestinal malabsorption or any other condition that might affect oral study\r\n             intervention absorption\r\n\r\n          -  Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose\r\n             of study intervention\r\n\r\n          -  Has any major hemorrhage or venous thromboembolic events within 3 months before the\r\n             first dose of study intervention. Participants with venous thrombosis diagnosed more\r\n             than 3 months before the first dose of study intervention must be on stable doses of\r\n             anticoagulants\r\n\r\n          -  Has a history of inflammatory bowel disease\r\n\r\n          -  Has a history of a gastrointestinal perforation within 6 months before the first dose\r\n             of study intervention\r\n\r\n          -  Is considered a poor medical risk due to a serious, uncontrolled medical disorder or\r\n             nonmalignant systemic disease\r\n\r\n          -  Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1),\r\n             anti-programmed cell death ligand 1 (anti-PD-L1), or anti programmed cell death ligand\r\n             2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory\r\n             T-cell receptor\r\n\r\n          -  Has received prior treatment (chemotherapy, radiotherapy, or surgical resection)\r\n             including investigational agents for SCLC\r\n\r\n          -  Is expected to require any other form of antineoplastic therapy for SCLC, including\r\n             radiation therapy, while on study\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study intervention\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks before the first dose of\r\n             study intervention\r\n\r\n          -  Has radiographic evidence of encasement or invasion of a major blood vessel, or of\r\n             intratumoral cavitation\r\n\r\n          -  Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who\r\n             is clinically stable following treatment for these conditions is eligible\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior the first dose of study intervention\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years\r\n\r\n          -  Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis. Participants with brain metastases may participate only if they satisfy\r\n             all of the following: a) Completed treatment at least 14 days before the first dose of\r\n             study intervention b) Have no evidence of new or enlarging brain metastases confirmed\r\n             by posttreatment repeat brain imaging performed at least 4 weeks after pretreatment\r\n             brain imaging, and c) Are neurologically stable without the need for steroids for at\r\n             least 7 days before the first dose of study intervention as per local site assessment.\r\n             Participants with untreated brain metastases will be allowed if they are asymptomatic,\r\n             the investigator determines there is no immediate CNS-specific treatment required,\r\n             there is no significant surrounding edema, and the brain metastases are of 5 mm or\r\n             less in size and 3 or fewer in number\r\n\r\n          -  Has a history of severe hypersensitivity reaction to any study intervention and/or any\r\n             of its excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n          -  Has a history of (noninfectious) pneumonitis/interstitial lung disease that required\r\n             steroids or has current pneumonitis/interstitial lung disease\r\n\r\n          -  Has a known history of, or active, neurologic paraneoplastic syndrome\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B\r\n             virus infection or an active Hepatitis C infection\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the study, interfere with the participant's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             the participant to participate, in the opinion of the treating investigator\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with the\r\n             participant's ability to cooperate with the requirements of the study\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"IV infusion"},{"intervention_type":"Biological","name":"Biological: MK-4830","description":"IV infusion"},{"intervention_type":"Biological","name":"Biological: MK-5890","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Oral capsule"},{"intervention_type":"Drug","name":"Drug: Etoposide","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"IV infusion"}],"outcomes":[{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 5 years","description":"OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)","time_frame":"Up to approximately 5 years","description":"ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented."},{"outcome_type":"primary","measure":"Six-Month Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1","time_frame":"Up to approximately 6 months","description":"Six-month PFS is defined as the survival without documented disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first at 6 months after randomization. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) as Assessed by BICR per RECIST 1.1","time_frame":"Up to approximately 5 years","description":"DOR is defined as the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) until first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) as Assessed by BICR per RECIST 1.1","time_frame":"Up to approximately 5 years","description":"PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented."},{"outcome_type":"secondary","measure":"Percent Change From Baseline in Tumor Size as Assessed by BICR","time_frame":"Baseline, 5 years","description":"Tumor size change is defined as the percent change from baseline in the sum of the diameters of the target lesions as assessed by BICR. Percent change from baseline in tumor size as assessed by BICR will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced an Adverse Event (AE)","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Treatment Due to an AE","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be presented."},{"outcome_type":"secondary","measure":"Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale (Items 29 and 30) at Week 19","time_frame":"Baseline, Week 19","description":"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question \"How would you rate your overall health during the past week?\" (Item 29) and the Quality of Life (QoL) question \"How would you rate your overall quality of life during the past week?\" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The mean change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented."}]}
{"nct_id":"NCT04851834","start_date":"2021-07-12","phase":"Phase 1/Phase 2","enrollment":125,"brief_title":"NTX-301 Monotherapy in Advanced Solid Tumours and in Combination With Platinum-based Chemotherapy in Advanced Ovarian & Bladder Cancer and in Combination With Temozolomide in High-grade Glioma","official_title":"A Phase 1/2, Open-label, Dose-exploration and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NTX-301 Monotherapy in Advanced Solid Tumours, and in Combination With Platinum-based Chemotherapy in Advanced Ovarian & Bladder Cancer, and in Combination With Temozolomide as Adjuvant (Maintenance) Therapy in High-grade Glioma (Optional Arm)","primary_completion_date":"2023-08-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-11-30","last_update":"2021-07-14","description":"This is a Phase 1/2, open-label, dose-exploration, combination/expansion study, which will start by evaluating the safety and tolerability of NTX-301, an oral DNMT1 inhibitor, as a monotherapy in patients with advanced solid tumours, who have failed treatment with available therapies known to be active for treatment of their corresponding disease. It will then explore the safety and tolerability of NTX-301 in combination with platinum-based therapy in patients with ovarian and bladder cancer. Optionally, the safety and tolerability of NTX-301 in combination with Temozolomide (TMZ) in patients with Isocitrate Dehydrogenase 1 (IDH1) mutated high-grade glioma will also be assessed.","other_id":"XNTR-20-02","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Dose escalation to determine MTD/RP2D, then dose expansion","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Ability to understand and be willing to sign an informed consent form.\r\n\r\n          2. Male or female,  18 years old at the time of screening.\r\n\r\n          3. Diagnosis of histologically or cytologically confirmed:\r\n\r\n               1. Locally advanced or metastatic cancer (all solid tumours). Patients must be\r\n                  considered refractory or intolerant to standard (SOC) therapies or have refused\r\n                  standard therapy (Phase 1a, Dose Escalation Monotherapy), OR\r\n\r\n               2. Locally advanced or metastatic cancer (ovarian or bladder cancer). Patients must\r\n                  be considered refractory or intolerant to standard (SOC) therapies or have\r\n                  refused standard therapy (Phase 1b, Dose & Disease Expansion Combination Arms,\r\n                  Arms 1 & 2), OR\r\n\r\n               3. High-grade glioma, such as glioblastoma multiforme (GBM) that are either: Newly\r\n                  diagnosed and are undergoing, or are planned to undergo, 42 days of standard of\r\n                  care (SOC) chemoradiation therapy as per part 1 of the eviQ protocol 3364 v.1.\r\n                  Patients successfully enrolled will receive a subsequent combination of NTX-301\r\n                  and Temozolomide on day 1 of their first 28-day cycle of part 2 of the eviQ\r\n                  protocol 3364 v.1. This combination arm replaces the Temozolomide monotherapy SOC\r\n                  maintenance therapy as described in Part 2 of the eviQ protocol 3364 v.1. In\r\n                  order to prevent any potential delays after radiotherapy, patients can be\r\n                  enrolled at any time during Chemoradiation (eviQ Part 1). In order to commence\r\n                  the TMZ combination arms the patient is required to complete the full 42 days of\r\n                  eviQ part 1, and also receive their first dose of the TMZ combination arm within\r\n                  the screening window. This timing can be adjusted based on medical need on a\r\n                  patient-by-patient basis as per the discretion of the principal investigator\r\n                  together with the approval of the medical monitor (Phase 1b, 2a, Dose & Disease\r\n                  Expansion Combination GBM (optional) Arm, Arms 3 & 4)\r\n\r\n             Note: patients must also have:\r\n\r\n             a. At least one measurable disease lesion per RECIST 1.1 &/or RANO criteria.\r\n\r\n          4. Eastern Cooperative Oncology Group performance status of 0 to 2 for Phase 1a, and 0 to\r\n             1 for Phase 1b, 2a.\r\n\r\n          5. Able to take oral medications and willing to record daily adherence to the study drug.\r\n\r\n          6. QT interval corrected using the Fridericia method (QTcF)  450 msec for males and \r\n             460 msec for females at screening and on Day 1, prior to dose administration (the mean\r\n             of triplicate measurements will be used to determine eligibility).\r\n\r\n          7. Evidence of adequate hepatic function at screening, as defined by the following:\r\n\r\n               1. AST and ALT 2.5  upper limit of normal (ULN) (5  ULN if liver metastases are\r\n                  present); and\r\n\r\n               2. Total bilirubin 1.5  ULN (< 2.0 x ULN for subjects with liver metastases or\r\n                  documented Gilbert's syndrome).\r\n\r\n          8. Adequate haematology laboratory assessment at screening, as defined by:\r\n\r\n               1. Absolute neutrophil count 1.00 x109/L;\r\n\r\n               2. Haemoglobin 90 g/L; and\r\n\r\n               3. Platelet count 100 x109/L.\r\n\r\n          9. Evidence of adequate renal function, as defined by a calculated creatinine clearance\r\n             50 mL/min using the Cockcroft-Gault equation or 24-hour urine collection with plasma\r\n             and urine creatinine concentrations respectively.\r\n\r\n         10. Adequate coagulation laboratory assessments (i.e., within normal reference range\r\n             values) at screening, in the opinion of the Investigator.\r\n\r\n         11. Female patients must be:\r\n\r\n               1. Of non-child-bearing potential i.e., surgically sterilized (hysterectomy,\r\n                  bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the\r\n                  Screening visit) or postmenopausal (where postmenopausal is defined as no menses\r\n                  for 12 months without an alternative medical cause and a follicle-stimulating\r\n                  hormone level consistent with postmenopausal status, per local laboratory\r\n                  guidelines), or\r\n\r\n               2. Of child-bearing potential, must agree not to attempt to become pregnant, must\r\n                  not donate ova, and, if engaging in sexual intercourse with a male partner, must\r\n                  agree to use an acceptable method(s) of contraception from signing the consent\r\n                  form until at least 45 days after the last dose of study drug.\r\n\r\n         12. Male patients must agree not to donate sperm and if engaging in sexual intercourse\r\n             with a female partner who could become pregnant, must agree to use an acceptable\r\n             method of contraception from signing the consent form until at least 90 days after the\r\n             last dose of study drug\r\n\r\n         13. Estimated life expectancy of at least 3 months, in the opinion of the Investigator.\r\n\r\n         14. Willing and able to comply with all scheduled visits, treatment plans, laboratory\r\n             tests, and other study procedures.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Investigational agents, including hypomethylating agents, in the past 5 half-lives\r\n\r\n          2. Patients with symptomatic brain metastases.\r\n\r\n          3. Uncontrolled pleural effusion(s), pericardial effusion or ascites. Note: if they are\r\n             controlled with recurrent drainage procedures, patients will be eligible for\r\n             enrolment.\r\n\r\n          4. Evidence of abnormal cardiac function as defined by any of the following:\r\n\r\n               1. Myocardial infarction within 6 months of Cycle 1, Day 1\r\n\r\n               2. Symptomatic congestive heart failure (New York Heart Association > class II)\r\n\r\n               3. Unstable angina\r\n\r\n               4. Cardiac arrhythmia requiring medication.\r\n\r\n          5. Unable to swallow oral medications.\r\n\r\n          6. Gastrointestinal (GI) conditions that, in the opinion of the Investigator, could\r\n             affect the absorption of NTX-301\r\n\r\n          7. History of bowel obstruction, abdominal fistula, gastrointestinal perforation or\r\n             intra-abdominal abscess within 6 months of the first administration of NTX-301 (Cycle\r\n             1, Day 1) (unless otherwise approved by the Investigator).\r\n\r\n          8. Use of any herbal or prescription medications, or consumption of foods known to be\r\n             strong inhibitors of cytochrome P450 3A (CYP3A) enzymes within 7 days prior to the\r\n             first administration of NTX-301 (Cycle 1, Day 1). These include (but are not limited\r\n             to):\r\n\r\n               1. Medications: refer to eMIMS Australia (www.emims.com.au)\r\n\r\n               2. Foods: Grapefruit or Seville orange (or grapefruit- or Seville orange-containing\r\n                  products, including juices).\r\n\r\n          9. Use of any herbal or prescription medications known to be strong inducers of CYP3A\r\n             enzymes within 7 days prior to the first administration of NTX-301 (Cycle 1, Day 1)\r\n             (refer to eMIMS Australia (www.emims.com.au)).\r\n\r\n         10. Clinically significant active infection within 2 weeks of the first dose of NTX-301\r\n             (Cycle 1, Day 1).\r\n\r\n         11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2),\r\n             hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the\r\n             Screening visit.\r\n\r\n         12. History of other malignancy within the past 2 years, with the following exceptions:\r\n\r\n               1. Malignancy treated with curative intent and with no known active disease present\r\n                  for  2 years before enrolment and felt to be at low risk for recurrence by the\r\n                  treating physician.\r\n\r\n               2. Adequately treated non-melanoma skin cancer or lentigo malignancy without\r\n                  evidence of disease.\r\n\r\n               3. Adequately treated cervical carcinoma in situ without evidence of disease.\r\n\r\n               4. Adequately treated breast ductal carcinoma in situ without evidence of disease.\r\n\r\n               5. Prostatic intraepithelial neoplasia without evidence of prostate cancer.\r\n\r\n               6. Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in\r\n                  situ.\r\n\r\n         13. Major surgery within 28 days of Cycle 1, Day1, with the following exceptions:\r\n\r\n             a. Major surgical procedures 28 days of beginning study drug, or Minor surgical\r\n             procedures 7 days. No waiting required following port-a-cath placement or for venous\r\n             access. Planned elective surgery unrelated to the patient's oncologic diagnosis, such\r\n             as hernia repair, may be allowed, at the discretion of the Investigator, as long as it\r\n             was performed at least 2 weeks prior to starting NTX-301, and the patient has\r\n             recovered fully from this procedure.\r\n\r\n         14. Received cancer-directed therapy within the following timeframes:\r\n\r\n               1. Anti-tumour therapy (chemotherapy, antibody therapy, molecular targeted therapy,\r\n                  hormonal therapy or investigational agent) within 28 days or (unless 5 times the\r\n                  half-life is shorter than 28 days); Note: concurrent use of hormone deprivation\r\n                  therapy for hormone-refractory prostate cancer, bisphosphonate or denosumab for\r\n                  skeletal related events per institution guideline is permitted.\r\n\r\n               2. Wide field radiation administered 28 days or limited field radiation for\r\n                  palliation 7 days prior to starting study drug or has not recovered from side\r\n                  effects of radiation therapy.\r\n\r\n               3. Receiving treatment with any other concurrent investigational device(s) or\r\n                  conventional agent(s) within 28 days (unless 5 times the half-life is shorter\r\n                  than 28 days) of Cycle 1, Day 1.\r\n\r\n         15. Adverse Events due to investigational or conventional agents >4 weeks earlier that\r\n             have not recovered to a severity of Grade 0 or Grade 1 (per Common Terminology\r\n             Criteria for Adverse Events (CTCAE) version 5.0 or higher), with the exception of\r\n             alopecia.\r\n\r\n             Notes (applies to Phase 1a, dose levels 3-5 and Phase 1b only):\r\n\r\n             i. Patients with chronic Grade 2 toxicities may be eligible per discretion of the\r\n             Investigator and Sponsor (e.g., Grade 2 chemotherapy induced neuropathy).\r\n\r\n             ii. Grade 2 or 3 toxicities from prior anti-tumour therapy that are considered\r\n             irreversible - defined as having been present and stable for > 6 months (such as\r\n             ifosfamide-related proteinuria) may be allowed if they are not otherwise described in\r\n             the exclusion criteria AND there is agreement to allow by both the Investigator and\r\n             Sponsor\r\n\r\n         16. For women of childbearing potential, a positive pregnancy test at screening, or on Day\r\n             1, prior to dose administration.\r\n\r\n         17. Pregnant or breast-feeding (or planning to breastfeed while on study through 15 days\r\n             after the last dose of study drug.\r\n\r\n         18. Hypersensitivity or other clinically significant reaction to the study drug or its\r\n             inactive ingredients.\r\n\r\n         19. Known substance abuse or medical, psychological, or social conditions that, in the\r\n             opinion of the Investigator, may interfere with the patient's participation in the\r\n             clinical study or evaluation of the clinical study results.\r\n\r\n         20. Any other condition or prior therapy that in the opinion of the Investigator would\r\n             make the patient unsuitable for this study, including inability to cooperate fully\r\n             with the requirements of the study protocol or likelihood of noncompliance with any\r\n             study requirements\r\n      ","sponsor":"Xennials Therapeutics Australia Pty Ltd","sponsor_type":"Industry","conditions":"Advanced Solid Tumor|Platinum-Resistant Ovarian Cancer|Platinum-Resistant Urothelial Carcinoma|High-grade Glioma","interventions":[{"intervention_type":"Drug","name":"Drug: NTX-301","description":"Oral hypomethylating agent"},{"intervention_type":"Drug","name":"Drug: Platinum-based Chemotherapy","description":"Standard of care for ovarian and bladder cancer"},{"intervention_type":"Drug","name":"Drug: Temozolomide","description":"Standard of care for high-grade glioma"}],"outcomes":[{"outcome_type":"primary","measure":"Safety & Tolerability: Incidence, type, and severity of Adverse Events (AE)","time_frame":"15 Months"},{"outcome_type":"primary","measure":"Safety & Tolerability: Dose-limiting Toxicities (DLT)","time_frame":"15 Months"},{"outcome_type":"secondary","measure":"Incidence of DLTs according to the MTD/RP2D evaluation process","time_frame":"12 Months"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Maximum observed concentration (Cmax)","time_frame":"12 Months"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Time to Cmax (Tmax)","time_frame":"12 Months"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Trough concentrations","time_frame":"12 Months"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Area under the concentration-time curve (AUC0-t)","time_frame":"12 Months"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Apparent terminal elimination half-life (t1/2)","time_frame":"12 Months"},{"outcome_type":"other","measure":"Tumour Response Assessment per RECIST 1.1 &/or RANO criteria","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Efficacy: Objective response rate (ORR)","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Efficacy: Disease control rate (DCR)","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Efficacy: Time to response (TTR)","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Efficacy: Duration of response (DOR)","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Efficacy: Progression free survival (PFS)","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Pharmacodynamics (PD): DNMT1 level","time_frame":"Up to 32 Months"},{"outcome_type":"other","measure":"Pharmacodynamics (PD): Global DNA Methylation","time_frame":"Up to 32 Months"}]}
{"nct_id":"NCT04787042","start_date":"2021-07-08","phase":"Phase 1/Phase 2","enrollment":198,"brief_title":"Phase 1a and Phase 2 Study for PK, PD, Safety and Preliminary Efficacy of ST-067","official_title":"A Phase 1a Open-Label, Dose-Escalation, and a Phase 2 Study to Investigate the Safety, PK, PD, and Clinical Activity of ST-067 Administered Subcutaneously as Monotherapy in Patients With Relapsed or Refractory Solid Tumors","primary_completion_date":"2023-05-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-07-30","last_update":"2021-07-29","description":"This is a multicenter Phase 1a open-label, dose escalation study, and a Phase 2 study of ST-067. Phase 1a is a first-in-human (FIH) dose escalation study in patients aged 18 years or older diagnosed with solid tumors who have exhausted available standard. Phase 2 will enroll patients aged 18 years or older diagnosed with the following solid tumors: melanoma, renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and microsatellite instability-high tumors.","other_id":"ST-067-001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Dose escalation and expansion","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Male and female patients aged 18 years\r\n\r\n          2. Must provide written informed consent and any authorizations required by local law\r\n\r\n          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          4. Have histologically or cytologically confirmed diagnosis of advanced/metastatic solid\r\n             tumor\r\n\r\n             For Phase 1a, the following solid tumors are allowed: Melanoma, Merkel cell, RCC,\r\n             urothelial, NSCLC,TNBC, SCCHN, microsatellite instability high, high tumor mutation\r\n             burden (Hi TMB) or mismatch repair deficient, gastric, cervical, endometrial,\r\n             cutaneous squamous, small cell lung, esophageal, hepatocellular carcinoma and platinum\r\n             resistant ovarian cancer.\r\n\r\n               1. For patients who have developed disease progression through standard therapy, or\r\n\r\n               2. For patients whom standard of care therapy that prolongs survival is not\r\n                  available or suitable (according to the investigator and after consultation with\r\n                  the Medical Monitor)\r\n\r\n             For Phase 2, the following solid tumors are allowed:\r\n\r\n             Melanoma, RCC, TNBC, NSCLC, SCCHN, and MSI-Hi tumors\r\n\r\n          5. Has at least 1 measurable lesion per RECIST 1.1 criteria which has not been biopsied\r\n             or received prior irradiation\r\n\r\n          6. Has an accessible tumor for biopsy pre- and on-treatment (mandatory).\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. History of another malignancy\r\n\r\n          2. Known symptomatic brain metastases requiring >10 mg/day of prednisolone\r\n\r\n          3. Significant cardiovascular disease\r\n\r\n          4. Significant ECG abnormalities i\r\n\r\n          5. Evidence of an ongoing systemic bacterial, fungal, or viral infection\r\n\r\n          6. Has received a live vaccine within 30 days\r\n\r\n          7. Major surgery within 4 weeks\r\n\r\n          8. Prior solid organ or bone marrow progenitor cell transplantation\r\n\r\n          9. Prior high dose chemotherapy requiring stem cell rescue\r\n\r\n         10. History of active autoimmune disorders\r\n\r\n         11. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids.\r\n      ","sponsor":"Simcha IL-18, Inc.","sponsor_type":"Industry","conditions":"Cancer|Solid Tumor|Melanoma|Renal Cell Carcinoma|Triple-negative Breast Cancer|Non Small Cell Lung Cancer|Squamous Cell Carcinoma of the Head and Neck|Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: ST-067","description":"ST-067 is an engineered variant of human interleukin-18."}],"outcomes":[{"outcome_type":"primary","measure":"Determine the maximum tolerated dose of ST-067 in phase 1a","time_frame":"Day 29","description":"6 to 12 patients have been enrolled at a dose level that is predicted to be the MTD"},{"outcome_type":"primary","measure":"Initial assessment of efficacy in phase 2","time_frame":"At 8 weeks","description":"Investigator-assessed ORR, defined as either a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on computed tomography (CT) or magnetic resonance imaging (MRI) scans"},{"outcome_type":"primary","measure":"Number of Participants With Treatment-Related Adverse Events","time_frame":"Day 29","description":"AE assessed by CTCAE 5.0"},{"outcome_type":"secondary","measure":"PK","time_frame":"Day 29","description":"Peak Plasma Concentration (Cmax)"},{"outcome_type":"secondary","measure":"ADA","time_frame":"Day 29","description":"Incidence of ADA to ST-067"}]}
{"nct_id":"NCT04799847","start_date":"2021-07-07","phase":"Phase 1/Phase 2","enrollment":167,"brief_title":"Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine","official_title":"A Multicenter, Non-randomized, Uncontrolled, Open-label Phase I/II Study to Observe the Safety and Preliminary Efficacy of Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine","primary_completion_date":"2023-11-22","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-11-27","last_update":"2021-03-18","description":"A Multicenter, Non-randomized, Uncontrolled, Open-label Phase I/II study to Observe the Safety and Preliminary Efficacy of Catumaxomab in Patients with Non-Muscle-Invasive Bladder Cancer who have Failed or are Intolerant to Bacillus Calmette-Guerin (BCG) Vaccine","other_id":"LP0190512","allocation":"N/A","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Signed and dated informed consent forms have been provided.\r\n\r\n          2. Willing to be complaint with the study procedures during the study.\r\n\r\n          3. Male or female, age  18 years old when signing informed consents.\r\n\r\n          4. Histologically or cytologically diagnosed as NMIBC, i.e., bladder cancer in the\r\n             following pTNM status: pTis, pTa, pT1.\r\n\r\n          5. Have received the standard therapy recommended in the current NMIBC clinical\r\n             guidelines, including intravesical BCG instillation, and diagnosed as BCG failure or\r\n             intolerance.\r\n\r\n          6. Have undergone standard TURBT + immediate intravesical chemotherapy before the signing\r\n             of ICF, with the absence of visible tumor lesion residues in the surgical field.\r\n\r\n          7. Recovered from any toxicity due to previous treatment (Grade 0-1 according to\r\n             NCI-CTCAE v 5.0).\r\n\r\n          8. Estimated life span is  6 months.\r\n\r\n          9. Eastern Oncology Cooperative Group (ECOG) performance status 0-1.\r\n\r\n         10. The laboratory test values during the screening period are in accordance with the\r\n             following table:\r\n\r\n               -  ANC(absolute neutrophil count)>=1.5x10^9/L\r\n\r\n               -  Hemoglobin>=80 g/L\r\n\r\n               -  Platelet>=100x10^9/L\r\n\r\n               -  Lymphocyte percentage>=20%\r\n\r\n               -  Serum Bilirubin <=1.25\r\n\r\n               -  ULN(or 2.5 ULN if there is Gilbert)\r\n\r\n               -  AST and ALT <=2.5 ULN without liver metastasisor<=5 ULN if liver metastasis)\r\n\r\n               -  Serum creatinine <=2.0 mg/dL or\r\n\r\n               -  Calculated creatinine clearance>=30 mL/min.\r\n\r\n         11. For women of childbearing potential: use an efficient method for contraception at\r\n             least 1 month prior to screening and agree to use this method for contraception during\r\n             the study period and 30 days after the last intravesical instillation.;\r\n\r\n         12. For men with fertility potential: use condoms or other methods to ensure effective\r\n             contraception for sexual partners from screening to 30 days after the last\r\n             intravesical instillation.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Known or suspected of being allergic to catumaxomab or similar antibodies.\r\n\r\n          2. Besides the TURBT + immediate postoperative infusion chemotherapy for this NMIBC\r\n             recurrence, participants received other anti-tumor treatments, including other\r\n             anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents,\r\n             hormone therapy, radiation therapy (excluding local radiation therapy for pain\r\n             relief), etc., the interval between the last instillation and the first intravesical\r\n             instillation is  21 days.\r\n\r\n          3. Tumor metastases outside the bladder confirmed in imaging examination.\r\n\r\n          4. With other primary malignant tumors diagnosed before the signing of ICF, excluding\r\n             squamous cell carcinoma in situ of skin or cervical carcinoma in situ without\r\n             recurrence within 5 years after resection.\r\n\r\n          5. The following diseases have not been resolved to CTCAE grade 0-1 in 3 days prior to\r\n             the first instillation:\r\n\r\n               -  Uncontrolled acute and chronic infections such as pneumonia, biliary infection,\r\n                  hepatitis B virus infection and hepatitis C virus infection, etc.\r\n\r\n               -  Dyspnea.\r\n\r\n               -  Acute /chronic renal injury.\r\n\r\n               -  Nephrotic syndrome.\r\n\r\n               -  Bladder perforation.\r\n\r\n               -  Urinary tract obstruction.\r\n\r\n          6. NYHA Class 3 or 4.\r\n\r\n          7. Related symptoms and signs of cardiovascular diseases: including myocardial\r\n             infarction, congestive heart failure, and arrhythmia.\r\n\r\n          8. Known cerebrovascular accidents.\r\n\r\n          9. History of autoimmune diseases (eg, inflammatory bowel disease, idiopathic\r\n             thrombocytopenic purpura, systemic lupus erythematosus, autologous hemolytic anemia,\r\n             rheumatoid arthritis, etc.).\r\n\r\n         10. Patients with known HIV serology positive, hepatitis C infection and/or hepatitis B\r\n             (Except the patients with positive HepBsAg or core antibody are responding to anti-HBV\r\n             treatment, they are allowed to participate in the study.\r\n\r\n             Notes: HepBsAg-negative patients at screening, or patients are undergoing treatment\r\n             with interferon-2a [IFN] or peginterferon-2a [Peg-IFN] and hepatitis B virus [HBV] DNA\r\n             < 2000 international units [IU], or partients who are receiving nucleoside [acid]\r\n             analogues at screening and HBV DNA below the lower limit of normal [LLN] are eligible\r\n             to participate in the study.\r\n\r\n         11. Pregnancy or breastfeeding during study treatment and follow-up period.\r\n\r\n         12. Patients with confirmed past history of neurological or psychotic disorders, including\r\n             epilepsy or dementia.\r\n\r\n         13. Other serious systemic conditions that may limit the participation in this study (e.g.\r\n             uncontrolled diabetes, cardiovascular and cerebrovascular disease, severe\r\n             gastrointestinal disease, and renal disease, etc.).\r\n      ","sponsor":"LintonPharm Co.,Ltd.","sponsor_type":"Industry","conditions":"Bladder Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Catumaxomab","description":"This study is conducted in 3 phases sequentially: dose escalation phase, dose expansion phase and dose extension phase. In the dose escalation phase, the preliminary safety and pharmacokinetic profile of catumaxomab by instillation, at 3 dose levels, in NMIBC patients are investigated."}],"outcomes":[{"outcome_type":"primary","measure":"Dose escalation phase and dose expansion phase only: DLT incidence.","time_frame":"28 days","description":"Dose Limited Toxicity"},{"outcome_type":"primary","measure":"1-year recurrence rate since the initial instillation","time_frame":"1 year","description":"1-year recurrence rate since the initial instillation"},{"outcome_type":"secondary","measure":"Recurrence rate at 3 months / 6 months / 2 years.","time_frame":"Up to 2 years","description":"Recurrence rate at 3 months / 6 months / 2 year"},{"outcome_type":"secondary","measure":"PFS","time_frame":"2 years","description":"Relapse-free survival"},{"outcome_type":"secondary","measure":"2-year progression rate to MIBC.","time_frame":"2 years","description":"2-year progression rate to MIBC."},{"outcome_type":"secondary","measure":"The incidence and severity of treatment-emergent adverse events (TEAEs)","time_frame":"2 years","description":"The incidence and severity of treatment-emergent adverse events (TEAEs) during intravesical instillation with catumaxomab are observed according to the National Cancer Institute Common Terminology Standard for Adverse Events (NCI-CTCAE) v5.0."},{"outcome_type":"secondary","measure":"ADA","time_frame":"2 years","description":"he incidence of anti-drug antibodies (ADA) to catumaxomab by intravesical instillation in serum."}]}
{"nct_id":"NCT04729387","start_date":"2021-07-02","phase":"Phase 3","enrollment":358,"brief_title":"Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected","official_title":"EPIK-O: A Phase III, Multi-center, Randomized (1:1), Open-label, Active-controlled, Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Olaparib as Compared to Single Agent Cytotoxic Chemotherapy, in Participants With no Germline BRCA Mutation Detected, Platinum-resistant or Refractory, High-grade Serous Ovarian Cancer","primary_completion_date":"2023-06-02","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-01-31","last_update":"2021-08-16","description":"The objective of this study is to assess the efficacy and safety of the combination of alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.","other_id":"CBYL719K12301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participant has histologically confirmed diagnosis of high-grade serous or high-grade\r\n             endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer\r\n\r\n          -  Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a\r\n             lesion at a previously irradiated site may only be counted as a target lesion if there\r\n             is clear sign of progression since the irradiation)\r\n\r\n          -  If no measurable disease is present, the disease should be assessable by Gynecologic\r\n             Cancer Intergroup criteria (GCIC) for CA-125\r\n\r\n          -  Participant has no germline BRCA1/2 mutation as determined by an FDA approved assay.\r\n\r\n          -  Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0\r\n             or 1\r\n\r\n          -  Participant has platinum-resistant (progression within one to six months after\r\n             completing platinum-based therapy) or platinum refractory disease (progression during\r\n             treatment or within 4 weeks after the last dose), where platinum-based therapy is not\r\n             an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions.\r\n             The platinum-based chemotherapy regimen does not necessarily need to be the last\r\n             regimen the participant received prior to study entry.\r\n\r\n          -  Participant must have received at least one but no more than three prior systemic\r\n             treatment regimens and for whom single-agent chemotherapy is appropriate as the next\r\n             line of treatment.\r\n\r\n          -  Participant has adequate bone marrow and organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor.\r\n\r\n          -  Participant is concurrently using other anti-cancer therapy\r\n\r\n          -  Participant is in a state of small or large bowel obstruction or has other impairment\r\n             of gastrointestinal (GI) function or GI disease\r\n\r\n          -  Participant has had surgery within 14 days prior to starting study drug or has not\r\n             recovered from major side effects\r\n\r\n          -  Participant has not recovered from all toxicities 5 related to prior anticancer\r\n             therapies to baseline or NCI CTCAE Version 4.03 Grade 1. Exception to this criterion:\r\n             participants with any grade of alopecia are allowed to enter the study.\r\n\r\n          -  Participants with liver impairment and Child Pugh score B or C\r\n\r\n          -  Participant has received radiotherapy  4 weeks or limited field radiation for\r\n             palliation 2 weeks prior to randomization, and who has not recovered to baseline,\r\n             grade 1 or better from related side effects of such therapy (with the exception of\r\n             alopecia).\r\n\r\n          -  Participant has a known hypersensitivity to any of the study drugs or excipients\r\n\r\n        Other inclusion/exclusion criteria may apply\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Alpelisib","description":"Alpelisib will be administered at 200 mg orally once daily following food on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Olaparib","description":"Olaparib will be administered at 200 mg orally twice daily irrespective of meals on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle."},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Paclitaxel will be administered at 80 mg/m2 as an intravenous infusion weekly during a 28-day treatment cycle, starting on Cycle 1 Day 1, and on Day 8, Day 15 and Day 22 of every cycle thereafter"},{"intervention_type":"Drug","name":"Drug: Pegylated liposomal doxorubicin (PLD)","description":"PLD will be administered at 40-50 mg/m2 (physician discretion) as an intravenous infusion once every 28-days in a 28 day treatment cycle, starting on Cycle 1 Day 1"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria","time_frame":"From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 23 months","description":"PFS is defined as the time from the date of randomization to the date of the first documented progression (based on RECIST 1.1 criteria) or death due to any cause. If a participant has not had an event, PFS will be censored at the date of the last adequate tumor assessment"},{"outcome_type":"secondary","measure":"Overall survival","time_frame":"From randomization until death, assessed up to approximately 44 months","description":"Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive"},{"outcome_type":"secondary","measure":"Number of participants with dose interruptions and dose reductions","time_frame":"From randomization until end of treatment, assessed up to approximately 18 months","description":"Tolerability measured by the number of participants who have dose interruptions and dose reductions"},{"outcome_type":"secondary","measure":"Dose intensity","time_frame":"From randomization until end of treatment, assessed up to approximately 18 months","description":"Tolerability measured by the dose intensity of study drug. Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure."},{"outcome_type":"secondary","measure":"Time to definitive deterioration of the Eastern Cooperative Oncology Group (ECOG) performance status (PS)","time_frame":"Up to approximately 18 months","description":"PS will be assessed using ECOG scale. The scale consists of 6 grades (from 0 to 5) where 0 implies fully active and 5 implies dead. Time to definitive deterioration in ECOG PS is defined as the time from the date of randomization to the date when ECOG PS has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or above."},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR) with confirmed response based on BIRC assessment according to RECIST 1.1 criteria","time_frame":"Up to approximately 23 months","description":"ORR with confirmed response is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per BIRC assessment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR) with confirmed response based on BIRC assessment according to RECIST 1.1","time_frame":"Up to approximately 23 months","description":"Clinical benefit rate (CBR) with confirmed response is defined as the proportion of participants with a best overall response of confirmed CR or PR, or stable disease (SD) lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per BIRC assessment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Time to response (TTR) based on BIRC assessment and according to RECIST 1.1","time_frame":"From the date of randomization to the first documented response, assessed up to approximately 23 months","description":"TTR is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR) based on tumor response data as per BIRC assessment and according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR) with confirmed response based on BIRC assessment and according to RECIST 1.1","time_frame":"From first documented response to first documented progression or death, assessed up to approximately 23 months","description":"DOR with confirmed response only applies to participants whose best overall response is confirmed CR or confirmed PR according to RECIST 1.1 based on tumor response data per BIRC assessment. The start date is the date of first documented response of CR or PR and the end date is defined as the date of the first documented progression or death due to underlying cancer"},{"outcome_type":"secondary","measure":"Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of alpelisib and olaparib","time_frame":"Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)","description":"The AUCtau will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib"},{"outcome_type":"secondary","measure":"Area under the curve from time zero to the last measurable concentration sampling time (AUClast)of alpelisib and olaparib","time_frame":"Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)","description":"The AUClast will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib"},{"outcome_type":"secondary","measure":"Maximum Concentration (Cmax) of alpelisib and olaparib","time_frame":"Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)","description":"The Cmax will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib"},{"outcome_type":"secondary","measure":"Time to reach maximum concentration (Tmax) of alpelisib and olaparib","time_frame":"Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)","description":"The Tmax will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib"},{"outcome_type":"secondary","measure":"Change from baseline in Function Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI)","time_frame":"From baseline up to approximately 44 months","description":"Health-related quality of life will be assessed by the Trial Outcome Index (TOI) of the Function Assessment of Cancer Therapy - Ovarian (FACT-O). The TOI is an index driven from FACT-O summarizing patients' physical and functional well-being as well as ovarian cancer-specific symptoms driven from FACT-O. The FACT-O TOI score ranges from 0 to 100 with higher scores indicating better quality of life."}]}
{"nct_id":"NCT04906395","start_date":"2021-07-01","phase":"Phase 3","enrollment":250,"brief_title":"Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer","official_title":"Phase 3,Single Arm,Open-Label Study Evaluating Ovarian Suppression Following 3 Month Leuprolide Acetate For Injectable Suspension (TOL2506) in Combination With Endocrine Therapy in Premenopausal Subjects With Hormone-Receptor-Positive (HR+),Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-31","last_update":"2021-09-17","description":"This is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. The study will also aim to assess administration of TOL2506 in men with HR+ breast cancer. Study duration, for individual subjects, will be up to 57 weeks, including a Screening Period of up to 9 weeks, a Treatment Period of 48 weeks, and an End of Study Visit (Visit 8, Week 48). Eligible subjects will enter into the Treatment Period in 1 of 2 groups: those who will receive tamoxifen concurrently with TOL2506 or those who will initiate therapy with an AI (letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, upon confirmation that estradiol (E2) levels of < 20 pg/mL have been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the discretion of the Investigator. However, a switch is not permitted 28 days prior to a dosing visit. At the end of the Treatment Period, subjects will be eligible for compassionate use of TOL2506 (expanded access) until TOL2506 receives marketing approval and is commercially available.","other_id":"TOL2506A","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":55,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Females\r\n\r\n               1. Able to understand the investigational nature of this study and provide written\r\n                  informed consent prior to the participation in the trial\r\n\r\n               2. Age 18 to 55, inclusive\r\n\r\n               3. Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or,\r\n                  PR>1%, HER2-negative per ASCO CAP guidelines)\r\n\r\n               4. Is a candidate for endocrine therapy + ovarian suppression\r\n\r\n               5. Is premenopausal at the time of study entry.\r\n\r\n                    -  E2 > 30 pg/mL\r\n\r\n                    -  Follicle stimulating hormone (FSH) < 40 IU/L\r\n\r\n                    -  Last menstrual period within the 3 months prior to first dose of TOL2506\r\n\r\n                  Exclusion Criteria:\r\n\r\n          -  Females\r\n\r\n               1. Body mass index (BMI) < 18.00 kg/m2 or > 35.00 kg/m2\r\n\r\n               2. Breastfeeding\r\n\r\n               3. Life expectancy < 12 months\r\n\r\n               4. Eastern Cooperative Oncology Group (ECOG) performance status  3\r\n\r\n               5. Unacceptable hepatic function as determined by any of the following:\r\n\r\n                    1. Alanine aminotransferase (ALT)  2X upper limit of normal (ULN)\r\n\r\n                    2. Aspartate aminotransferase (AST)  2X ULN\r\n\r\n                    3. Bilirubin  2X ULN\r\n\r\n                    4. Alkaline phosphatase  2X ULN\r\n\r\n                    5. Severe hepatic impairment (Child-Pugh Class C)\r\n\r\n               6. Unacceptable renal function as determined by any of the following:\r\n\r\n                    1. Creatinine  3X ULN\r\n\r\n                    2. Creatinine clearance  30 mL/minute\r\n\r\n                    3. Creatinine clearance  60 mL/minute in subjects with bone density 1.5\r\n                       standard deviations below the young adult normal mean\r\n\r\n               7. History of significantly abnormal ECG or screening 12-lead ECG demonstrating any\r\n                  of the following:\r\n\r\n                    1. HR > 100 BPM\r\n\r\n                    2. QRS > 120 msec\r\n\r\n                    3. QTc > 450 msec\r\n\r\n                    4. PR > 220 msec\r\n\r\n               8. Prior (within 28 days prior to Day 0) and/or concomitant use of medications known\r\n                  to prolong the QT/QTc interval\r\n\r\n               9. Prior use of tamoxifen, other SERMs (eg, raloxifene) or antagonists (eg,\r\n                  fulvestrant), aromatase inhibitor, mammalian target of rapamycin (mTOR)\r\n                  inhibitors, or hormone replacement therapy within 3 months before breast cancer\r\n                  diagnosis\r\n\r\n              10. Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer\r\n\r\n              11. History of treatment for osteopenia/osteoporosis\r\n\r\n              12. Prior or current use of drugs or supplements known to increase bone mineral\r\n                  density (ie, bisphosphonates, denosumab, teriparatide, abaloparatide,\r\n                  romosozumab, calcitonin, fluoride, strontium)\r\n\r\n              13. Low trauma fracture(s) occurring within 12 months prior to Screening (defined as\r\n                  a fracture that results from a fall from a standing height or less, excluding\r\n                  fingers, toes, face and skull)\r\n\r\n              14. Conditions that preclude bone mineral density measurement (lumbar spine/bilateral\r\n                  hip surgery with hardware in place, abdominal clips, umbilical ring [not willing\r\n                  to remove] or weight that exceeds the DEXA machine limitation)\r\n\r\n              15. Any other medical condition or serious illness, presence of a second malignancy\r\n                  under current treatment or follow-up, or the presence of clinically significant\r\n                  findings on the physical exam, laboratory testing, medical history (including\r\n                  conditions that may be associated with low bone mass), that in the opinion of the\r\n                  Investigator may interfere with trial conduct, subject safety, or interpretation\r\n                  of study results\r\n\r\n              16. Already receiving and/or previously received GnRH analogs within 1 year before\r\n                  breast cancer diagnosis\r\n\r\n              17. Psychiatric, addictive, or other disorders that would preclude study compliance\r\n\r\n              18. Use of medications that may impact subject safety and/or affect the PK of the\r\n                  drug and hormonal assessments including but not limited to:\r\n\r\n                    1. Oral or transdermal hormonal therapy within 30 days prior to Screening\r\n\r\n                    2. Estrogen, progesterone, or androgens within 30 days prior to Screening\r\n\r\n                    3. Hormonal contraceptives within 30 days prior to Screening\r\n\r\n                    4. Medications known to result in clinically important decreases in bone mass\r\n                       taken within 6 months prior to Screening\r\n\r\n              19. Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH\r\n                  agonist/analogs or to any of the components of the IP\r\n\r\n              20. Sexually active with a male partner and not willing to use non-hormonal\r\n                  contraceptive methods throughout the study\r\n\r\n              21. Is of childbearing potential with a positive serum pregnancy test at Screening or\r\n                  urine pregnancy test at Day 0\r\n\r\n              22. Exposure to any investigational agent within 30 days prior to the first dose of\r\n                  TOL2506\r\n\r\n        See contact information to obtain inclusion/exclusion criteria for males\r\n      ","sponsor":"Tolmar Inc.","sponsor_type":"Industry","conditions":"Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TOL2506","description":"Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months."},{"intervention_type":"Drug","name":"Drug: Tamoxifen","description":"20 mg once daily or 10 mg 2 times daily - either tablet or solution"},{"intervention_type":"Drug","name":"Drug: Letrozole Tablets","description":"One 2.5 mg tablet taken orally once daily"},{"intervention_type":"Drug","name":"Drug: Anastrozole Tablets","description":"One 1 mg tablet taken orally once daily"},{"intervention_type":"Drug","name":"Drug: Exemestane Tablets","description":"One 25 mg tablet taken orally once daily"}],"outcomes":[{"outcome_type":"primary","measure":"Suppression of ovarian function (E2 levels and menses status)","time_frame":"6 weeks after the first administration of TOL2506","description":"E2 levels < 20 pg/mL at Week 6 and absence of menses after Week 5"},{"outcome_type":"secondary","measure":"Suppression of ovarian function overall (E2 and absence of menses; treatments pooled)","time_frame":"Week 6 to Week 48","description":"Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48"},{"outcome_type":"secondary","measure":"Suppression of ovarian function overall (E2 and absence of menses; TOL2506 + tamoxifen)","time_frame":"Week 6 to Week 48","description":"Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + tamoxifen at every measurement from Week 6 to Week 48"},{"outcome_type":"secondary","measure":"Suppression of ovarian function overall (E2 and absence of menses; TOL2506 + aromatase inhibitor)","time_frame":"Week 6 to Week 48","description":"Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + aromatase inhibitor at every measurement from Week 6 to Week 48"},{"outcome_type":"secondary","measure":"Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses + treatments pooled)","time_frame":"Weeks 12, 24, 36, and 48","description":"Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) assessed individually at weeks 12, 24, 36 and 48"},{"outcome_type":"secondary","measure":"Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses; TOL2506 + tamoxifen)","time_frame":"Weeks 12, 24, 36, and 48","description":"Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + tamoxifen assessed individually at weeks 12, 24, 36 and 48"},{"outcome_type":"secondary","measure":"Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses; TOL2506 + aromatase inhibitor)","time_frame":"Weeks 12, 24, 36, and 48","description":"Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + aromatase inhibitor assessed individually at weeks 12, 24, 36 and 48"}]}
{"nct_id":"NCT04908787","start_date":"2021-06-30","phase":"Phase 3","enrollment":357,"brief_title":"A Phase III Study of BD0801 Combined With Chemotherapy in Recurrent, Platinum-resistant Epithelial Ovarian Cancer","official_title":"A Randomized, Double-blind, Phase III Study of BD0801 Injection Combined With Chemotherapy Versus Placebo Combined With Chemotherapy in Patients With Recurrent, Platinum-resistant Epithelial Ovarian, Fallopian Tube , or Primary Peritoneal Cancer.","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-12-31","last_update":"2021-06-04","description":"The standard systemic treatment for ovarian cancer is platinum-based chemotherapy. However, majority of patients relapse and eventually progress to platinum resistance. In patients with platinum-resistant or refractory ovarian cancer, effective treatment options are limited and the prognosis is very poor. Angiogenesis is essential for tumor growth and metastasis, and VEGF/VEGF receptor(VEGFR) signaling pathway is the most promising angiogenic target. This study aim to assess the efficacy and safety of the combination BD0801 and chemotherapy in patients with platinum-resistant recurrent ovarian cancer.","other_id":"SIM-63-OC-301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  female patients, >/=18 years of age;\r\n\r\n          -  epithelial ovarian, fallopian tube or primary peritoneal cancer;\r\n\r\n          -  platinum-resistant disease (disease progression within <6 months of platinum therapy)\r\n\r\n          -  Eastern Cooperative Oncology GroupECOGperformance status of 0-1\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  non-epithelial tumours\r\n\r\n          -  ovarian tumours with low malignant potential\r\n\r\n          -  previous treatment with >2 chemotherapy regimens\r\n\r\n          -  prior radiotherapy to the pelvis or abdomen within 5 years\r\n      ","sponsor":"Jiangsu Simcere Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: BD0801","description":"Subjects receive BD0801 , intravenously, d1, d15, q4w, Dosage form: injectable, Strength: 1.5 mg/kg"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Subjects receive Weekly Paclitaxel, intravenously, d1, d8, d15, d22, q4w, Dosage form: injectable, Strength: 80 mg/m2"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Subjects receive Placebo, intravenously, d1, d15, q4w, Dosage form: injectable, Strength: 1.5 mg/kg"},{"intervention_type":"Drug","name":"Drug: Topotecan","description":"Subjects receive Topotecan, intravenously, d1, d8, d15, q4w, Dosage form: injectable, Strength: 4mg/m2"},{"intervention_type":"Drug","name":"Drug: doxorubicin liposome","description":"Subjects receive doxorubicin liposome, intravenously, d1, , q4w, Dosage form: injectable, Strength: 40mg/m2"}],"outcomes":[{"outcome_type":"primary","measure":"Progression free survival(PFS) by blinded independent review committee(BIRC)","time_frame":"2 year","description":"PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the IRC according to the RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"2.5 year","description":"OS is the time interval from the date of randomization to death from any cause."},{"outcome_type":"secondary","measure":"PFS by investigator","time_frame":"2 year","description":"PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigator according to the RECIST1.1 criteria"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by investigator","time_frame":"2 year","description":"Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) by investigator","time_frame":"2 year","description":"Proportion of subjects who have a complete or partial response, or stable disease relative to baseline as assessed by investigator according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Objective Response Rate (DOR) by investigator","time_frame":"2 year","description":"Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria."},{"outcome_type":"secondary","measure":"ORR by BIRC","time_frame":"2 year","description":"Proportion of subjects who have a complete or partial response relative to baseline as assessed by BIRC according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"DCR by BIRC","time_frame":"2 year","description":"Proportion of subjects who have a complete or partial response, or stable disease relative to baseline as assessed by BIRC according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"DOR by BIRC","time_frame":"2 year","description":"Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria."},{"outcome_type":"secondary","measure":"The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)","time_frame":"2.5 year","description":"Frequency and severity of Adverse Events or Serious Adverse Events as defined by CTCAE version 5.0"},{"outcome_type":"secondary","measure":"Quality Of Life (QoL)","time_frame":"2.5 year","description":"use European Organisation for Research and Treatment of Cance（EORTC）- QLQ-C30 questionnaire"},{"outcome_type":"secondary","measure":"Quality Of Life (QoL)","time_frame":"2.5 year","description":"use EORTC-QLQ-OV28 questionnaire"},{"outcome_type":"secondary","measure":"Serum drug concentrations of BD0801","time_frame":"2 year","description":"Serum drug concentrations of BD0801 will be calculated."},{"outcome_type":"secondary","measure":"rate of immunogenicity positive reaction","time_frame":"2 year"},{"outcome_type":"secondary","measure":"duration of immunogenicity positive reaction","time_frame":"2 year"}]}
{"nct_id":"NCT04887870","start_date":"2021-06-30","phase":"Phase 2/Phase 3","enrollment":200,"brief_title":"Study of Sitravatinib With or Without Other Anticancer Therapies Receiving Clinical Benefit From Parent Study","official_title":"A Multicenter, Open-label Rollover Study of Sitravatinib Alone or in Combination With Other Anticancer Therapies in Patients With Advanced or Metastatic Solid Malignancies","primary_completion_date":"2024-02-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-02-29","last_update":"2021-09-08","description":"A Study of Sitravatinib Alone or in Combination with Other Anticancer Therapies in Advanced or Metastatic Malignancies","other_id":"516-014","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Currently receiving sitravatinib single- agent or in combination with other\r\n             therapeutic agent(s) in another Mirati- sponsored protocol\r\n\r\n          -  Currently tolerating the treatment regimen in the parent protocol\r\n\r\n          -  Experiencing clinical benefit with or without prior radiographic progression from the\r\n             treatment regimen in the parent protocol in the opinion of the investigator and the\r\n             investigator determines that continuing treatment is in the patient's best interest\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known or suspected presence of other cancer\r\n\r\n          -  Other life- threatening illness or organ system dysfunction compromising safety\r\n             evaluation\r\n      ","sponsor":"Mirati Therapeutics Inc.","sponsor_type":"Industry","conditions":"Advanced or Metastatic Solid Malignancies","interventions":[{"intervention_type":"Drug","name":"Drug: Sitravatinib","description":"Sitravatinib is a small molecule inhibitor of recepor tyrosine kinases."},{"intervention_type":"Drug","name":"Drug: Nivolumab","description":"Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody"},{"intervention_type":"Drug","name":"Drug: Enfortumab Vedotin-Ejfv","description":"Enfortumab is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a monoclonal antibody conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE)"},{"intervention_type":"Drug","name":"Drug: Ipilimumab","description":"Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody"}],"outcomes":[{"outcome_type":"primary","measure":"Frequency of subjects experiencing treatment-related AEs.","time_frame":"24 Months","description":"Frequency of subjects experiencing treatment-related AEs."},{"outcome_type":"secondary","measure":"Time to clinical or radiographic progression on study.","time_frame":"24 Months","description":"Time to clinical or radiographic progression on study."}]}
{"nct_id":"NCT04861779","start_date":"2021-06-30","phase":"Phase 1","enrollment":126,"brief_title":"A Study of HSK29116 in Adults With Relapsed/Refractory B-cell Malignancies","official_title":"A Phase Ia/b Clinical Study on Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of BTK Protein Degradation Agent HSK29116 in Subjects With Relapsed or Refractory B-Cell Malignancy","primary_completion_date":"2023-08-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-10-31","last_update":"2021-06-03","description":"This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of HSK29116 in patients with advanced B-cell malignancies.","other_id":"HSK29116-101","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Males or females, of any race, aged  18 years.\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0- 2.\r\n\r\n          -  Sufficient bone marrow function, hepatic function and Coagulation function.\r\n\r\n          -  Patients must have measurable disease per disease-specific response criteria.\r\n\r\n          -  Have histologically confirmed R/R CLL,SLL,MCL,Non-GCB DLBCL,FL(grade 1- 3a),MZL,WM.\r\n\r\n          -  Received at least 1 prior systemic therapy(MCL no more than 5 lines of treatment) and\r\n             have no other therapies known to provide clinical benefit.\r\n\r\n          -  After the most recent treatment regimen, it is confirmed that PR has not been\r\n             achieved, or there is confirmed progressive disease.\r\n\r\n          -  Must require systemic therapy.\r\n\r\n          -  The pregnancy test (urine or serum) of female subjects of childbearing potential shall\r\n             be negative before enrollment.\r\n\r\n          -  Female subjects of childbearing potential and fertile male subjects shall adopt one of\r\n             the following highly effective contraception measures during the entire study and\r\n             within 90 days after the study treatment is ended: abstinence, intrauterine device, or\r\n             hormonal contraceptives beginning at least 3 months before the first dose of IMP.Male\r\n             subjects are prohibited from donating sperm from the start of study treatment to 90\r\n             days after the end of treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects with central nervous system involvement.\r\n\r\n          -  Subjects with histopathological transformation.\r\n\r\n          -  Receipt of allogeneic hematopoietic stem cell transplantation  180 days before the\r\n             start of study treatment administration on Cycle 1, Day 1, unless the subject is no\r\n             longer on immunosuppressant medication. History of autologous hematopoietic stem cell\r\n             transplantation within 12 weeks (84 days) before the start of study treatment.\r\n\r\n          -  Continuous immunosuppressive therapy, including systemic (such as intravenous or oral)\r\n             treatment with corticosteroids for the underlying diseases within 2 weeks before the\r\n             first dose.\r\n\r\n          -  Received any chemotherapy, biological therapy (such as monoclonal antibodies),\r\n             immunotherapy, Chinese herbal medicines with anti-tumor efficacy, or other anti-tumor\r\n             treatments within 4 weeks before the first use of HSK29116. The time interval from the\r\n             last dose of BTK inhibitor or experimental small molecule drug to the first dose of\r\n             the IMP is 5 times shorter than the half-life of the previously used drug.\r\n\r\n          -  Previously developed toxicity due to anticancer treatment that did not resolve to\r\n             Grade  1 (as per NCI-CTCAE 5.0), except for AEs not constituting a safety risk as\r\n             assessed by the investigator.\r\n\r\n          -  A history of other malignant tumors within 2 years before enrollment, except for basal\r\n             cell carcinoma or skin squamous cell carcinoma having been adequately treated, or\r\n             without disease for  2 years or with other types of cancer with the survival time of\r\n             greater than 2 years. Subjects with breast or prostate cancer who are on maintenance\r\n             hormonal therapies following therapeutic procedures with curative intent are\r\n             permitted.\r\n\r\n          -  Uncontrolled systemic active infections, or other infections or still on intravenous\r\n             anti-infection treatment.\r\n\r\n          -  Underwent major surgery in the past 4 weeks.\r\n\r\n          -  Known infection with human immunodeficiency virus, or serologic status reflecting\r\n             active hepatitis B or C infection.\r\n\r\n          -  Subjects with severe cardiovascular diseases within 6 months before screening.\r\n\r\n          -  Left Ventricular Ejection Fraction < 50% based on either echocardiogram or multigated\r\n             acquisition (MUGA) scan.\r\n\r\n          -  QTcF  450 msecs for males and QTcF  470 msec for females or other significant ECG\r\n             abnormalities.\r\n\r\n          -  Clinically significant gastrointestinal abnormalities that may affect the intake,\r\n             transport, or absorption of drugs.\r\n\r\n          -  Requiring or received anticoagulant therapy with warfarin or equivalent vitamin K\r\n             antagonists (such as phenprocoumon) within 7 days before the first study treatment.\r\n\r\n          -  Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. Known\r\n             history of bleeding diathesis.\r\n\r\n          -  A history of stroke or intracranial hemorrhage within 6 months before the first study\r\n             treatment.\r\n\r\n          -  Use of CYP3A4 inhibitor or inducer within 7 days before the first study treatment, or\r\n             using of sensitive substrates metabolized by CYP3A4/CYP2B6.\r\n      ","sponsor":"Haisco Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Relapsed/Refractory B-Cell Malignancies","interventions":[{"intervention_type":"Drug","name":"Drug: HSK29116","description":"Oral HSK29116"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants with Protocol Specified Dose-Limiting Toxicities","time_frame":"1 year","description":"Phase 1a"},{"outcome_type":"primary","measure":"To establish the MTD and/or recommended Phase 1b dose of HSK29116","time_frame":"1 year","description":"Phase 1a"},{"outcome_type":"primary","measure":"Number of Participants with Adverse Events and Clinical Laboratory Abnormalities","time_frame":"Up to 3 years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Pharmacokinetic(PK) Profile of HSK29116: Maximum Serum Concentration","time_frame":"At the end of Cycle 1 (each cycle is 28 days)","description":"Phase1a/1b-Sampling of the first dose, pre and post-dose at selected cycle"},{"outcome_type":"secondary","measure":"Overall response rate(ORR) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Duration of response(DoR) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Progression-free survival(PFS) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Time to response(TTR) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"}]}
{"nct_id":"NCT04854499","start_date":"2021-06-30","phase":"Phase 2","enrollment":233,"brief_title":"Study of Magrolimab Combination Therapy in Participants With Head and Neck Squamous Cell Carcinoma","official_title":"A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-07-02","description":"The study consists of Safety Run-in and Phase 2 Cohorts. The primary objectives of the safety run-in cohorts of this study are to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with pembrolizumab + 5-fluorouracil (5-FU) + platinum chemotherapy, and docetaxel in combination with magrolimab in participants with head and neck squamous cell carcinoma (HNSCC). Phase 2 Cohorts 1: To evaluate the progression-free survival (PFS) with magrolimab in combination with pembrolizumab + 5-FU + platinum versus pembrolizumab + 5-FU + platinum as assessed by independent central review. Phase 2 Cohorts 2 and 3: To evaluate the efficacy of magrolimab in combination with pembrolizumab and magrolimab in combination with docetaxel as determined by the investigator-assessed objective response rate (ORR).","other_id":"GS-US-548-5916","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed metastatic or locally recurrent HNSCC that\r\n             is considered incurable by local therapies\r\n\r\n        Safety Run-in Cohort 1 and Phase 2 Cohorts 1\r\n\r\n          -  HNSCC per protocol specified inclusion criteria regardless of PD-L1 status\r\n\r\n          -  HNSCC per protocol specified inclusion criterion with a PD-L1 CPS  1\r\n\r\n        Safety Run-in Cohort 2 and Phase 2 Cohort 3\r\n\r\n          -  Histologically or cytologically confirmed locally advanced/mHNSCC regardless of PD-L1\r\n             status with at least 1 and no more than 2 lines of prior systemic anticancer therapy\r\n             in the locally advanced/metastatic setting\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Active central nervous system (CNS) disease (individuals with asymptomatic and stable,\r\n             treated CNS lesions who have been off corticosteroids, radiation, or other\r\n             CNS-directed therapy for at least 4 weeks are not considered active)\r\n\r\n          -  History of (noninfectious) pneumonitis that required steroids or current pneumonitis\r\n\r\n        Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab\r\n        (if Applicable), and Phase 2 Cohorts 1 and 2\r\n\r\n          -  Prior treatment with any of the following:\r\n\r\n               -  Anti-programmed cell death protein 1 or anti-PD-L1 checkpoint inhibitors\r\n\r\n               -  Anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitors\r\n\r\n               -  5-FU and platinum-based chemotherapy (Safety Run-in Cohort 1 and Phase 2 Cohorts\r\n                  1 only)\r\n\r\n        Safety Run-in Cohort 2 and Phase 2 Cohort 3\r\n\r\n          -  Progressive disease within 6 months of completion of curatively intended systemic\r\n             treatment for locally advanced/mHNSCC\r\n\r\n          -  Prior treatment with a taxane\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"Gilead Sciences","sponsor_type":"Industry","conditions":"Head and Neck Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Magrolimab","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: 5-FU","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Administered intravenously"}],"outcomes":[{"outcome_type":"primary","measure":"Safety Run-in Cohorts: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0","time_frame":"First Dose up to 21 days"},{"outcome_type":"primary","measure":"Phase 2 Cohorts 1: Progression-free survival (PFS)","time_frame":"Up to 5 years","description":"PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as assessed by independent central review, or death from any cause, whichever occurs first."},{"outcome_type":"primary","measure":"Phase 2 Cohorts 2 and 3: Objective Response Rate (ORR)","time_frame":"Up to 9 months","description":"ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as determined by investigator assessment."},{"outcome_type":"secondary","measure":"Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab","time_frame":"Up to end of treatment (approximately 24 months)"},{"outcome_type":"secondary","measure":"Safety Run-In and Phase 2 Cohorts: Percentage of Participants who Developed Antidrug Antibodies (ADAs) to Magrolimab","time_frame":"Up to end of treatment (approximately 24 months)"},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Objective Response Rate (ORR)","time_frame":"Up to 9 months","description":"ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as determined by independent central review."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Progression-free survival (PFS)","time_frame":"Up to 5 years","description":"PFS is defined as the time from the date of randomization (Phase 2 Cohorts 1) or date of dose initiation (Phase 2 Cohorts 2 and 3) until the earliest date of documented disease progression as determined by investigator assessment per RECIST, version 1.1, or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Duration of Response (DOR)","time_frame":"Up to 5 years","description":"DOR is defined as the time from first documentation of CR or PR to the earliest date of documented disease progression or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Overall Survival (OS)","time_frame":"Up to 5 years","description":"OS is defined as the time from the date of randomization (Phase 2 Cohorts 1) or time from the date of dose initiation (Phase 2 Cohorts 2 and 3) to death from any cause."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Change from Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) Score","time_frame":"Baseline; up to 24 months","description":"The EORTC QLQ-C30 questionnaire is a specific questionnaire for cancer, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant)."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Change from Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life - Head and Neck Module (EORTC QLQ-H&N35)","time_frame":"Baseline; up to 24 months","description":"The head & neck cancer module is a 35-item questionnaire designed for use among a wide range of participants with head & neck cancer, varying in disease stage and treatment modality. It includes 7 multi-item scales that assess pain (4 items), swallowing (4 items), senses (2 items), speech (3 items), social eating (4 items), social contact (5 items), and sexuality (2 items). There are also 11 single items. Using a 4-point Likert scale, participants indicate the degree to which they have experienced symptoms. For all items and scales, high scores indicate more problems."},{"outcome_type":"secondary","measure":"Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)","time_frame":"Baseline; up to 24 months","description":"The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive part and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state.\r\nThe EQ-VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating \"the worst health you can imagine\" and 100 indicating \"the best health you can imagine.\" Higher scores of EQ VAS indicate better health."}]}
{"nct_id":"NCT04964934","start_date":"2021-06-30","phase":"Phase 3","enrollment":302,"brief_title":"Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)","official_title":"A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor (Palbociclib or Abemaciclib) vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study","primary_completion_date":"2023-09-28","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-06-25","last_update":"2021-09-21","description":"The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib or abemaciclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation","other_id":"D8534C00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally\r\n             recurrent or metastatic disease not amenable to resection or radiation therapy with\r\n             curative intent.\r\n\r\n          -  Documentation of histologically confirmed diagnosis of estrogen receptor positive\r\n             (ER+) /HER2- breast cancer based on local laboratory results.\r\n\r\n          -  Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib or\r\n             abemaciclib)  LHRH as the initial endocrine based treatment for advanced disease\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1.\r\n\r\n          -  ESR1m positive detected by central testing of ctDNA\r\n\r\n          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory\r\n             tests, and other study procedures.\r\n\r\n          -  Adequate organ and marrow function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Advanced, symptomatic, visceral spread, that are at risk of life-threatening\r\n             complications in the short term.\r\n\r\n          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or\r\n             leptomeningeal disease.\r\n\r\n          -  Any evidence of severe or uncontrolled systemic diseases which, in the investigator's\r\n             opinion, makes it undesirable for the participant to participate in the study or that\r\n             would jeopardize compliance with the protocol.\r\n\r\n          -  Patient with known or family history of severe heart disease\r\n\r\n          -  Previous treatment with AZD9833, investigational SERDs or fulvestrant.\r\n\r\n          -  Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.\r\n\r\n          -  Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor\r\n             and/or AI treatment.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"ER-Positive HER2-Negative Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AZD9833","description":"Dosage formulation: AZD9833 tablets will be administered orally"},{"intervention_type":"Drug","name":"Drug: AZD9833 Placebo","description":"Dosage formulation: AZD9833 placebo tablets will be administrated orally."},{"intervention_type":"Drug","name":"Drug: Anastrozole","description":"Dosage formulation: anastrozole tablets will be administered orally."},{"intervention_type":"Drug","name":"Drug: Anastrozole placebo","description":"Dosage formulation: anastrozole placebo tablets will be administrated orally."},{"intervention_type":"Drug","name":"Drug: Letrozole","description":"Dosage formulation: letrozole tablets will be administered orally."},{"intervention_type":"Drug","name":"Drug: Letrozole placebo","description":"Dosage formulation: letrozole placebo tablets will be administered orally."},{"intervention_type":"Drug","name":"Drug: Palbociclib","description":"Dosage formulation: palbociclib tablets/capsules will be administered orally"},{"intervention_type":"Drug","name":"Drug: Abemaciclib","description":"Dosage formulation: abemaciclib tablets will be administered orally"},{"intervention_type":"Drug","name":"Drug: Luteinizing hormone-releasing hormone (LHRH) agonist","description":"Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST version 1.1)","time_frame":"From randomization until the earlier of the progression event or death (approximately 2 years)","description":"PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death."},{"outcome_type":"secondary","measure":"Progression-free survival 2 (PFS2)","time_frame":"From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (approximately 3.5 years)","description":"PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From randomization until the date of death due to any cause (approximately 5 years)","description":"The OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Chemotherapy free survival","time_frame":"From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 5 years)","description":"Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause."},{"outcome_type":"secondary","measure":"Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1","time_frame":"From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (approximately 5 years)","description":"ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1."},{"outcome_type":"secondary","measure":"Clinical benefit rate at 24 weeks (CBR24)","time_frame":"At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)","description":"CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for At least 23 weeks after randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)"},{"outcome_type":"secondary","measure":"Change from baseline in EORTC QLQ-C30 scale scores","time_frame":"From baseline until second progression (approximately 5 years)","description":"Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden."},{"outcome_type":"secondary","measure":"Change from baseline in EORTC QLQ-BR23 scale scores","time_frame":"From baseline until second progression (approximately 5 years)","description":"Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden."},{"outcome_type":"secondary","measure":"Plasma concentration of AZD9833 at specified timepoints","time_frame":"on Day 15 for each patient","description":"To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration."}]}
{"nct_id":"NCT04862780","start_date":"2021-06-29","phase":"Phase 1/Phase 2","enrollment":120,"brief_title":"(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC","official_title":"A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients With EGFR Mutant Non-Small Cell Lung Cancer","primary_completion_date":"2025-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-01-31","last_update":"2021-09-01","description":"This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor.","other_id":"BLU-945-1101","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. 18 years of age at the time of signing the informed consent.\r\n\r\n          2. Pathologically confirmed, definitively diagnosed, metastatic NSCLC harboring an\r\n             activating EGFR mutation.\r\n\r\n          3. Previously received at least 1 prior EGFR-targeted TKI. For patients enrolled to\r\n             expansion Group 2, prior treatment must include an approved EGFR-targeted TKI with\r\n             activity against the T790M mutation, such as osimertinib.\r\n\r\n          4. EGFR mutation profile determined locally via a Sponsor-approved testing methodology,\r\n             using either tumor tissue (ideally from a progressing lesion) and/or ctDNA in plasma.\r\n             It is preferable that samples used for analysis be obtained during or after disease\r\n             progression on the last EGFR-targeted TKI received.\r\n\r\n               1. Dose escalation: At each dose level, slots may be reserved for patients with the\r\n                  mutations of interest.\r\n\r\n               2. Expansion Groups: Patients must have NSCLC harboring EGFR T790M and C797S\r\n                  mutation (Group 1); EGFR T790M but not C797S (Group 2); or EGFR C797S but not\r\n                  T790M (Group 3).\r\n\r\n          5. Pretreatment tumor sample (either an archival sample or a sample obtained by\r\n             pretreatment biopsy) submitted for central analysis. It is preferable that\r\n             pretreatment tumor samples be obtained from a progression lesion, during or after\r\n             disease progression on the last EGFR-targeted TKI received.\r\n\r\n             Patients without archival tissue available, where biopsy is not considered safe and/or\r\n             medically feasible, may be discussed with the study medical monitor and may be\r\n             approved for enrollment on a case-by-case basis.\r\n\r\n          6. Phase 2 Expansion Groups: Patient has at least 1 measurable target lesion evaluable by\r\n             RECIST 1.1 as assessed by the investigator.\r\n\r\n          7. Eastern Cooperative Oncology Group (ECOG) performance status is 0-2.\r\n\r\n          8. Agrees to use contraception consistent with local regulations\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Tumor harbors any additional known primary driver alterations including but not\r\n             limited to pathologic abnormalities of EGFR exon 20, KRAS, BRAF V600E, NTRK1/2/3,\r\n             HER2, ALK, ROS1, MET, or RET.\r\n\r\n          2. NSCLC with mixed squamous cell histology as well as tumors with histologic\r\n             transformation (NSCLC to SCLC and with epithelial to mesenchymal transition).\r\n\r\n          3. Received the following anticancer therapy:\r\n\r\n               1. EGFR-targeted TKI within 7 days prior to the first dose of study drug.\r\n\r\n               2. Any immunotherapy or other antibody therapy (including EGFR-targeted antibodies\r\n                  or bi-specific antibodies) within 28 days prior to the first dose of study drug\r\n                  (immune-related toxicities must have resolved to < Grade 2 prior to starting BLU\r\n                  945).\r\n\r\n               3. Any other systemic anticancer therapy within 14 days or 5 half-lives prior to the\r\n                  first dose of study drug, whichever is the shortest, but with a minimum of 7 days\r\n                  in all circumstances. BLU 945 may be started within these washout periods if\r\n                  considered by the Investigator to be safe and within the best interest of the\r\n                  patient, with prior Sponsor approval.\r\n\r\n               4. Radiotherapy to a large field or including a vital organ (including whole brain\r\n                  radiotherapy or stereotactic radiosurgery to brain) within 14 days before the\r\n                  first dose of study drug. Participant received radiotherapy to a focal site of\r\n                  disease that did not include a vital organ (such as a limb) within 7 days before\r\n                  the first dose of study drug.\r\n\r\n          4. CNS metastases or spinal cord compression that is associated with progressive\r\n             neurological symptoms or requires increasing doses of corticosteroids to control the\r\n             CNS disease. If a patient requires corticosteroids for management of CNS disease, the\r\n             dose must have been stable for the 2 weeks preceding treatment. Asymptomatic untreated\r\n             CNS and leptomeningeal disease is allowed and, when measurable, should be captured as\r\n             target lesions.\r\n\r\n          5. Any of the following abnormalities on the latest laboratory test prior to the first\r\n             dose of study drug (ie, within 7 days prior to Cycle 1 Day 1 [C1D1]):\r\n\r\n               1. Absolute neutrophil count (ANC) <1.0109/L.\r\n\r\n               2. Platelet count <75109/L.\r\n\r\n               3. Hemoglobin 8.0 g/dL (red blood cell transfusion and erythropoietin may be used\r\n                  to reach at least 8.0 g/dL, but must have been administered at least 2 weeks\r\n                  prior to the first dose of study drug).\r\n\r\n               4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 the upper\r\n                  limit of normal (ULN) if no hepatic metastases are present; >5 ULN if hepatic\r\n                  metastases are present.\r\n\r\n               5. Total bilirubin >1.5 ULN; >3 ULN in presence of Gilbert's disease.\r\n\r\n               6. Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min.\r\n\r\n               7. International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds\r\n                  above control or a patient-specific INR or PT abnormality that the treating\r\n                  investigator considers clinically relevant and/or increases the risk for\r\n                  hemorrhage in that individual patient.\r\n\r\n          6. Known intracranial hemorrhage and/or bleeding diatheses.\r\n\r\n          7. Clinically active ongoing interstitial lung disease (ILD) of any etiology, including\r\n             drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of\r\n             study treatment. Patients with prior ILD associated with clinically resolved COVID 19\r\n             infection may be enrolled upon discussion with, and approval by, the Medical Monitor.\r\n\r\n          8. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria\r\n             for Adverse Events (CTCAE) Grade 1 or that have not resolved to baseline at the time\r\n             of starting study. Exceptions include alopecia and fatigue, and, upon discussion with\r\n             and approval by the Medical Monitor, other toxicities that are not thought to present\r\n             a risk to patient safety.\r\n\r\n          9. Mean resting QT interval corrected using Fridericia's formula (QTcF) >470 msec, a\r\n             history of prolonged QT syndrome or Torsades de pointes, or a familial history of\r\n             prolonged QT syndrome.\r\n\r\n         10. Clinically significant, uncontrolled, cardiovascular disease including congestive\r\n             heart failure Grade III or IV according to the New York Heart Association\r\n             classification; myocardial infarction or unstable angina within the previous 6 months,\r\n             uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias,\r\n             including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree\r\n             heart block or third degree heart block).\r\n\r\n         11. History of another primary malignancy (other than completely resected carcinomas in\r\n             situ) that has been diagnosed or required therapy within 2 years prior to initiation\r\n             of study treatment. However, upon discussion with the sponsor, the following\r\n             categories of patients with prior malignancy are eligible to participate:\r\n\r\n               1. Patients with a previous malignancy that completed all anticancer treatment at\r\n                  least 2 years before and with no evidence of residual disease from the prior\r\n                  malignancy at registration\r\n\r\n               2. Patients who have another concurrent malignancy (not lung cancer) that is\r\n                  clinically stable and does not require tumor-directed treatment. (Examples\r\n                  include, but are not limited to, completely resected basal cell carcinoma and\r\n                  squamous cell carcinoma of skin, curatively treated prostate cancer, and early\r\n                  gastric cancer cured by endoscopic mucosal resection or endoscopic submucosal\r\n                  dissection.)\r\n\r\n         12. Active, uncontrolled infection (viral, bacterial, or fungal) or active tuberculosis,\r\n             hepatitis B, hepatitis C, AIDS-related illness, or known COVID 19 infection.\r\n             Controlled infections, including HIV and \"cured\" hepatitis C (no active fever, no\r\n             evidence of systemic inflammatory response syndrome) that are stable on antiviral\r\n             treatment may be eligible if benefit/risk is justified and permission is granted from\r\n             the Sponsor.\r\n\r\n         13. Received neutrophil or platelet growth factor support within 14 days of the first dose\r\n             of study drug.\r\n\r\n         14. Requires treatment with a prohibited medication or herbal remedy (as specified in\r\n             Appendix 2) that cannot be discontinued at least 2 weeks before the start of study\r\n             drug administration. BLU 945 may be started within 14 days or 5 half-lives of these\r\n             therapies if considered by the Investigator to be safe and within the best interest of\r\n             the patient, with prior Sponsor approval.\r\n\r\n         15. Major surgical procedure within 14 days of the first dose of study drug (procedures\r\n             such as central venous catheter placement, tumor needle biopsy, and feeding tube\r\n             placement are not considered major surgical procedures).\r\n      ","sponsor":"Blueprint Medicines Corporation","sponsor_type":"Industry","conditions":"Lung Neoplasms|Carcinoma, Non-Small-Cell Lung|Respiratory Tract Neoplasms|Neoplasms|Neoplasms by Site|Lung Diseases|Respiratory Tract Disease|Carcinoma, Bronchogenic|Bronchial Neoplasms|Adenocarcinoma|Carcinoma|Neoplasms by Histologic Type|Neoplasms, Nerve Tissue|EGFR T790M|EGFR C797S|EGFR L858R|EGFR Gene Mutation|EGF-R Positive Non-Small Cell Lung Cancer|EGFR Exon 19 Deletion|EGFR Mutation Resulting in Tyrosine Kinase Inhibitor Resistance|EGFR Activating Mutation|Protein Kinase Inhibitors|Antineoplastic Agents|Thoracic Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: BLU-945","description":"Oral administration"}],"outcomes":[{"outcome_type":"primary","measure":"[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-945","time_frame":"Up to 12 months","description":"MTD determination: dose limiting toxicity (DLT) rate"},{"outcome_type":"primary","measure":"[Phase 1] Determine recommended Phase 2 dose (RP2D) of BLU-945","time_frame":"Up to 12 months","description":"RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data"},{"outcome_type":"primary","measure":"[Phase 1] Rate and severity of adverse events","time_frame":"Up to 12 months"},{"outcome_type":"primary","measure":"[Phase 2] Overall response rate (ORR)","time_frame":"Up to 30 months","description":"ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1"},{"outcome_type":"secondary","measure":"[Phase 1] Overall response rate (ORR)","time_frame":"Up to 12 months","description":"ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Duration of response (DOR)","time_frame":"Up to 42 months","description":"DOR, defined as the time from first documented response of complete response (CR) or partial response (PR) to the date of first documented progressive disease or death due to any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Cmax","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Tmax","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Tlast","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] AUC (0-24)","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Ctrough","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Vz/F","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] T 1/2","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] CL/F","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] R","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 1 and Phase 2] Assess treatment-induced modulation of EGFR pathway biomarkers.","time_frame":"Up to 42 months","description":"Profile pharmacodynamic changes in the EGFR pathway biomarker expression levels of dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4)."},{"outcome_type":"secondary","measure":"[Phase 2] Disease control rate (DCR)","time_frame":"Up to 30 months","description":"DCR, defined as the proportion of patients who experience a best response of CR, PR, or stable disease (SD) according to RECIST 1.1"},{"outcome_type":"secondary","measure":"[Phase 2] Clinical benefit rate (CBR)","time_frame":"Up to 30 months","description":"CBR, defined as the proportion of patients who experience a confirmed CR or PR, or stable disease (SD) with a duration of at least 16 weeks according to RECIST 1.1"},{"outcome_type":"secondary","measure":"[Phase 2] Progression free survival (PFS)","time_frame":"Up to 42 months","description":"PFS, defined as the time from the first dose of BLU-945 until the date of first documented progressive disease or death due to any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"[Phase 2] Overall survival (OS)","time_frame":"Up to 42 months","description":"OS, defined as the time from the first dose of BLU-945 until the date of death due to any cause"},{"outcome_type":"secondary","measure":"[Phase 2] Assess intracranial rate","time_frame":"Up to 42 months","description":"In accordance with RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"[Phase 2] Assess time to intracranial progression","time_frame":"Up to 42 months","description":"In accordance with RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"[Phase 2] Rate and severity of adverse events","time_frame":"Up to 42 months"},{"outcome_type":"secondary","measure":"[Phase 2] QTc Assessment","time_frame":"Up to 25 months","description":"Effects of BLU-945 on ECG parameters extracted from continuous 12 lead Holter recordings"}]}
{"nct_id":"NCT04870112","start_date":"2021-06-28","phase":"Phase 1/Phase 2","enrollment":124,"brief_title":"A Study to Evaluate Subcutaneous Durvalumab in Patients With Non-Small Cell Lung Cancer and Small Cell Lung Cancer","official_title":"A Phase 1/2a, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of Subcutaneous Durvalumab in Patients With Non-Small Cell and Small Cell Lung Cancer - SCope-D1","primary_completion_date":"2024-01-19","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-19","last_update":"2021-09-13","description":"This study has 2 parts: dose finding and dose confirmatory. In Part 1, the dose finding phase of the study, there will be 3 or more dosing levels to find out what dose of durvalumab administered as an infusion under the skin acts similarly to durvalumab administered into a vein. 24 participants with Non-Small Cell Lung Cancer will be enrolled for a 12 month treatment period and 3 months follow up. In Part 2, the dose confirmation phase of the study, participants will receive the dose of durvalumab identified in Part 1 of the study. The goal of Part 2 will be to learn more about the way that the body processes durvalumab when administered as an infusion under the skin. Approximately 90 participants with Non-Small Cell Lung Cancer will be enrolled; additionally, up to 10 participants with Small Cell Lung Cancer (who will receive concurrent chemotherapy) will be enrolled for a 12 treatment period and a 3 month follow-up period.","other_id":"D9072C00001","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically documented unresectable Stage III NSCLC that has not\r\n             progressed following definitive platinum based CRT or extensive disease (Stage IV)\r\n             SCLC\r\n\r\n          -  ECOG performance status of 0 or 1\r\n\r\n          -  For participants with SCLC: At least 1 lesion, not previously irradiated, that\r\n             qualifies as a RECIST 1.1 TL at baseline\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of allogeneic organ transplantation\r\n\r\n          -  Autoimmune or inflammatory disorders, diverticulitis, systemic lupus erythematosus,\r\n             Sarcoidosis syndrome, or Wegener syndrome\r\n\r\n          -  Uncontrolled intercurrent illness\r\n\r\n          -  History of another primary malignancy\r\n\r\n          -  History of active primary immunodeficiency\r\n\r\n          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human\r\n             immunodeficiency virus (HIV)\r\n\r\n          -  Brain metastases or spinal cord compression\r\n\r\n          -  Persistent toxicities (CTCAE Grade >2) caused by previous anticancer therapy,\r\n             excluding alopecia\r\n\r\n          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer|Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"Anti-PD-L1 antibody"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Chemotherapy"},{"intervention_type":"Drug","name":"Drug: Etoposide","description":"Chemotherapy"}],"outcomes":[{"outcome_type":"primary","measure":"Observed serum concentration (Ctrough)","time_frame":"Approximately 16 months"},{"outcome_type":"primary","measure":"Number of patients with injection site reactions and immune-mediated reactions","time_frame":"Approximately 16 months"},{"outcome_type":"primary","measure":"Maximum observed serum concentration (Cmax)","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Time to maximum observed serum concentration (tmax) of durvalumab","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Incidence of Adverse Events","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Changes in WHO/ECOG performance status","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Occurrence of abnormal ECG - PR, QRS, QT, and QT interval corrected by Fridericia's formula intervals","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in clinical chemistry","time_frame":"Approximately 16 months","description":"Clinical chemistry will be assessed by liver function(Alanine aminotransferase, Aspartate aminotransferase, albumin, total bilirubin), kidney function (e.g. Urea, Creatinine) and endocrine function(TSH, T3 free,T4 free)"},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in haematology","time_frame":"Approximately 16 months","description":"Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count."},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (blood pressure in mmHg)","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (pulse rate) in beats per minute","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (respiration rate) in breaths per minute","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (temperature) in degrees Celsius","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Incidence of of anti-drug antibodies (ADA) and neutralizing antibodies","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Part 2 only: Overall Response Rate (ORR) - proportion of participants with a complete or partial response to treatment as determined using RECIST 1.1 guidelines","time_frame":"Approximately 16 months"},{"outcome_type":"secondary","measure":"Part 2 only: Best Objective Response (BoR) - participant's best response following first dose of study drug","time_frame":"Approximately 16 months"},{"outcome_type":"other","measure":"Incidence of injection site reactions reported through ISQ Symptoms questionnaire","time_frame":"Approximately 16 months"},{"outcome_type":"other","measure":"Treatment satisfaction reported using ISQ Satisfaction questionnaire","time_frame":"Approximately 16 months"}]}
{"nct_id":"NCT04895722","start_date":"2021-06-25","phase":"Phase 2","enrollment":240,"brief_title":"Evaluation of Pembrolizumab (MK-3475) or Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008)","official_title":"A Phase 2, Multicenter, Multi Arm, Study to Evaluate Pembrolizumab (MK-3475) or MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)","primary_completion_date":"2024-09-19","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-09-19","last_update":"2021-09-10","description":"The purpose of this study is to assess the efficacy and safety of pembrolizumab or co-formulated pembrolizumab/quavonlimab in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.","other_id":"1308A-008","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by\r\n             American Joint Committee on Cancer [AJCC] version 8)\r\n\r\n          -  Has locally confirmed dMMR/MSI-H\r\n\r\n          -  Has a life expectancy of at least 3 months\r\n\r\n          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 at\r\n             screening and within 3 days before Cycle 1 Day 1\r\n\r\n          -  Female participants are eligible to participate if not pregnant or breastfeeding, and\r\n             not a woman of childbearing potential (WOCBP), or if a WOCBP then is using a\r\n             contraceptive method that is highly effective or is abstinent on a long-term and\r\n             persistent basis, during the intervention period and for at least 120 days after the\r\n             last dose of study intervention\r\n\r\n          -  Has measurable disease per RECIST 1.1 as assessed by BICR\r\n\r\n          -  Has adequate organ function\r\n\r\n        Cohort A:\r\n\r\n          -  Has been previously treated for their disease and radiographically progressed per\r\n             RECIST 1.1 on or after or could not tolerate standard treatment, which must include\r\n             all of the following agents if approved and locally available in the country where the\r\n             participant is randomized:\r\n\r\n               -  Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as\r\n                  equivalent to fluorouracil in prior therapy)\r\n\r\n               -  With or without an anti-vascular endothelial growth factor (VEGF) monoclonal\r\n                  antibody (e.g., bevacizumab)\r\n\r\n               -  At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal\r\n                  antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog\r\n                  (RAS) wild-type participants with left-sided tumors\r\n\r\n          -  Must not have had prior exposure to PD-1 or PD-L1 therapies as treatment for this\r\n             disease\r\n\r\n        Cohort B:\r\n\r\n        - Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for\r\n        this disease\r\n\r\n        Cohort C:\r\n\r\n          -  Has radiographically progressed on-treatment with an anti-PD-1 monoclonal antibody\r\n             (mAb) administered either as monotherapy or in combination with other therapies\r\n\r\n          -  Has had 0 to 1 prior systemic fluoropyrimidine based chemotherapy regimens\r\n\r\n          -  Must not have been treated in Cohort A\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has received prior therapy with an agent directed to another stimulatory or\r\n             coinhibitory T-cell receptor\r\n\r\n          -  Has received prior systemic anticancer therapy including investigational agents within\r\n             4 weeks before the first dose of study intervention\r\n\r\n          -  Has not recovered adequately from a surgery procedure, and/or has any complications\r\n             from a prior surgery before starting study intervention\r\n\r\n          -  Has received prior radiotherapy within 2 weeks of start of study intervention\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study intervention\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks before the first dose of\r\n             study intervention\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior to the first dose of study medication\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 2 years\r\n\r\n          -  Has known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis\r\n\r\n          -  Has severe hypersensitivity (Grade 3) to pembrolizumab, quavonlimab and/or any of\r\n             their excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive\r\n             drugs)\r\n\r\n          -  Has a history of (noninfectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or\r\n             bacterial infections, etc.)\r\n\r\n          -  Has a known history of Human Immunodeficiency Virus (HIV) infection\r\n\r\n          -  Has known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive\r\n             and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) or active\r\n             Hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected or\r\n             anti-HCV antibodypositive) infection\r\n\r\n          -  Is pregnant, or breastfeeding, or expecting to conceive children within the projected\r\n             duration of the study, starting with the Screening Visit through 120 days after the\r\n             last dose of study intervention\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Colorectal Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"400 mg pembrolizumab administered via IV infusion."},{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Quavonlimab","description":"Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion."}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 39 months","description":"ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 39 months","description":"DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 39 months","description":"PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 assessed by BICR or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 39 months","description":"OS is defined as the time from randomization (or first dose) to death due to any cause."},{"outcome_type":"secondary","measure":"Number of participants who experienced an Adverse Event (AE)","time_frame":"Up to approximately 27 months","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants with an AE will be reported."},{"outcome_type":"secondary","measure":"Number of participants discontinuing study treatment due to an AE","time_frame":"Up to approximately 24 months","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants that discontinue study treatment due to an AE will be reported."}]}
{"nct_id":"NCT04785820","start_date":"2021-06-25","phase":"Phase 2","enrollment":255,"brief_title":"A Study of RO7121661 and RO7247669 Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus","official_title":"A 3-Arm, Randomized, Blinded, Active-Controlled, Phase II Study of RO7121661, a PD1-TIM3 Bispecific Antibody and RO7247669, a PD1-LAG3 Bispecific Antibody, Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus","primary_completion_date":"2024-08-20","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-08-20","last_update":"2021-09-05","description":"This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.","other_id":"BP42772","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Major lesion was histologically confirmed esophageal squamous-cell carcinoma (ESCC)\r\n\r\n          -  Patients who have previously received 1 line of treatment with either a\r\n             fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in\r\n             non-curative intention prior to randomization; or patients who received treatment with\r\n             a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had\r\n             recurrence within 24 weeks after the last dose of the treatment\r\n\r\n          -  Radiologically measurable disease according to RECIST v1.1. Previously irradiated\r\n             lesions should not be counted as target lesions unless clearly progressed after the\r\n             radiotherapy\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1\r\n\r\n          -  A life expectancy of at least ()12 weeks\r\n\r\n          -  Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1)\r\n             tumor positivity\r\n\r\n          -  Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must\r\n             have resolved to Grade 1, except alopecia (any grade), vitiligo, endocrinopathy\r\n             managed with replacement therapy, and Grade 2 peripheral neuropathy\r\n\r\n          -  Adequate cardiovascular, hematological, liver, and renal function\r\n\r\n          -  Serum albumin 25 grams per liter (g/L),\r\n\r\n          -  For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and\r\n             activated partial thromboplastin time 1.5 times () the upper limit of normal (ULN);\r\n             for participants receiving therapeutic anticoagulation: stable anticoagulant regimen\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant, not\r\n             breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to\r\n             remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods\r\n             during the treatment period and for at least 5 months after the final dose of study\r\n             drug and have a negative pregnancy test (blood) within the 7 days prior to\r\n             randomization.\r\n\r\n          -  A male participant must remain abstinent (refrain from heterosexual intercourse) or\r\n             use contraceptive measures such as a condom plus an additional contraceptive method\r\n             and refrain from donating sperm during the treatment period and for at least 5 months\r\n             after the final dose of study drug\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Pregnancy, lactation, or breastfeeding\r\n\r\n          -  Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab,\r\n             including but not limited to, hypersensitivity to Chinese hamster ovary cell products\r\n             or other recombinant human or humanized antibodies\r\n\r\n          -  Patients with significant malnutrition. Patients whose nutrition has been well\r\n             controlled for 28 days prior to randomization may be enrolled\r\n\r\n          -  Evidence of complete esophageal obstruction not amenable to treatment\r\n\r\n          -  Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent\r\n             organs (aorta or tracheobronchial tree)\r\n\r\n          -  Symptomatic central nervous system (CNS) metastases\r\n\r\n          -  Spinal cord compression not definitively treated with surgery and/or radiation or\r\n             without evidence that disease has been clinically stable for 14 days prior to\r\n             randomization\r\n\r\n          -  Active or history of carcinomatous meningitis/leptomeningeal disease\r\n\r\n          -  Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or\r\n             enzyme inducing anticonvulsants in the last 28 days prior to randomization\r\n\r\n          -  Uncontrolled tumor-related pain. Participants requiring pain medication must be on a\r\n             stable regimen at study entry\r\n\r\n          -  Active second malignancy (with some exceptions)\r\n\r\n          -  Evidence of significant, uncontrolled concomitant diseases that could affect\r\n             compliance with the protocol or interpretation of results, including diabetes\r\n             mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune\r\n             deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary\r\n             fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).\r\n\r\n          -  Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed\r\n             consent\r\n\r\n          -  Significant cardiovascular/cerebrovascular disease within 6 months prior to\r\n             randomization\r\n\r\n          -  Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but\r\n             not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or\r\n             other infection (excluding fungal infections of nail beds) or any major episode of\r\n             infection requiring treatment with intravenous (IV) antibiotics or hospitalization\r\n             (relating to the completion of the course of antibiotics, except if for tumor fever)\r\n             within 28 days prior to randomization\r\n\r\n          -  Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis,\r\n             and inherited liver disease.\r\n\r\n          -  Major surgical procedure or significant traumatic injury (excluding biopsies) within\r\n             28 days prior to randomization, or anticipation of the need for major surgery during\r\n             the course of the study\r\n\r\n          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical\r\n             laboratory finding giving reasonable suspicion of a disease or condition that\r\n             contraindicates the use of an investigational drug or that may affect the\r\n             interpretation of the results or render the participant at high risk from treatment\r\n             complications\r\n\r\n          -  Dementia or altered mental status that would prohibit informed consent\r\n\r\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent\r\n             drainage procedures (expected to occur once monthly or more frequently)\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  Positive human immunodeficiency virus (HIV) test at screening\r\n\r\n          -  Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core\r\n             antibody (HBcAb) test at screening\r\n\r\n          -  Positive hepatitis C virus (HCV) antibody test at screening\r\n\r\n          -  Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors\r\n             (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)\r\n\r\n          -  Vaccination with live vaccines within 28 days prior to randomization, or anticipation\r\n             that a live attenuated vaccine will be required during the study\r\n\r\n          -  Treatment with therapeutic oral or IV antibiotics within 14 days prior to\r\n             randomization\r\n\r\n          -  Concurrent therapy with any other investigational drug (defined as treatment for which\r\n             there is currently no regulatory authority approved indication) 28 days or 5\r\n             half-lives of the drug (whichever is shorter) prior to randomization\r\n\r\n          -  Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives\r\n             or 28 days (whichever is shorter) prior to randomization\r\n\r\n          -  Regular immunosuppressive therapy (i.e., for organ transplantation, chronic\r\n             rheumatologic disease)\r\n\r\n          -  Radiotherapy within the last 28 days before start of study drug treatment is not\r\n             allowed, with the exception of limited palliative radiotherapy\r\n\r\n          -  Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T\r\n             cells (CAR-T) therapies\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Advanced or Metastatic Esophageal Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: RO7121661","description":"2100 milligrams (mg) administered by intravenous (IV) infusion once every 2 weeks on Day 1 of each 14-day cycle."},{"intervention_type":"Drug","name":"Drug: RO7247669","description":"2100 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle."},{"intervention_type":"Drug","name":"Drug: Nivolumab","description":"240 mg administered by IV infusion once every 2 weeks on Day 1 of each 14-day cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival, Defined as the Time from Randomization to Death from Any Cause","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Number of Participants with Adverse Events, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR), Defined as the Percentage of Participants with a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR), Defined as the Percentage of Participants with an Objective Response or Stable Disease According to RECIST v1.1","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Duration of Response for Participants with ORR, Defined as the Time from the First Occurrence of a Documented Objective Response to Disease Progression According to RECIST v1.1 or Death from any Cause, Whichever Occurs First","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS), Defined as the Time from Randomization to the First Occurrence of Progression as Determined According to RECIST v1.1 or Death from any Cause, Whichever Occurs First","time_frame":"Up to 3 years, 4 months"},{"outcome_type":"secondary","measure":"Percentage of Participants Reporting Clinically Meaningful Improvement in Global Health Status/Quality of Life (GHS/QoL), and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-C30","time_frame":"Baseline (Day 1 of Cycle 1) and Day 1 of Cycles 4, 7, and 10 (each cycle is 14 days); then every 3 months until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years)","description":"EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30"},{"outcome_type":"secondary","measure":"Percentage of Participants Reporting a Clinically Meaningful Improvement in GHS/QoL, and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC IL97 Questionnaire","time_frame":"Baseline (Cycle 1 Day 1) and Day 1 of Cycles 2, 3, 5, 6, 8, and 9 (each cycle is 14 days)","description":"EORTC IL97 = European Organisation for Research and Treatment of Cancer - Item Library 97"},{"outcome_type":"secondary","measure":"Percentage of Participants Reporting a Clinically Meaningful Improvement in Dysphagia, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-OES18","time_frame":"Baseline (Cycle 1 Day 1) and Day 1 of each subsequent treatment cycle (each cycle is 14 days) until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years)","description":"EORTC QLQ-OES18 = European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Esophageal Cancer"},{"outcome_type":"secondary","measure":"Serum Concentrations of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Area Under the Time-Serum Concentration Curve (AUC) of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Maximum Serum Concentrations of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Total Clearance of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Volume of Distribution at Steady State of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Terminal Half-Life of RO7121661, RO7247669, and Nivolumab","time_frame":"Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Number of Participants with Anti-Drug Antibodies (ADAs) to RO7121661, RO7247669, or Nivolumab at Baseline and During the Study","time_frame":"Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 4, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Number of T-cell Subsets by Phenotype and Activation Status (CD4/CD8 HLA-DR+Ki67+) in the Peripheral Blood","time_frame":"Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Number of CD8+ T-cells Infiltrating the Tumor Microenvironment","time_frame":"Baseline and Day 1 of Cycle 3 (each cycle is 14 days)"},{"outcome_type":"secondary","measure":"Change from Baseline in the Number of CD8+ T-cells Proliferating (CD8+Ki67+) in the Tumor Microenvironment","time_frame":"Baseline and Day 1 of Cycle 3 (each cycle is 14 days)"},{"outcome_type":"secondary","measure":"Baseline PDL1, CD8+PD1+, CD8+TIM3+, and CD8+LAG3+ Expression in the Tumor Microenvironment","time_frame":"At Baseline"}]}
{"nct_id":"NCT04844749","start_date":"2021-06-24","phase":"Phase 3","enrollment":245,"brief_title":"Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent","official_title":"VERACITY - Randomized, Active-Controlled, Phase 3 Study of VERU-111 for the Treatment of Metastatic Castration-Resistant Prostate Cancer in Patients Who Have Failed Prior Treatment With at Least One Androgen Receptor Targeting Agent","primary_completion_date":"2024-04-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-08-19","last_update":"2021-09-20","description":"To demonstrate the efficacy of VERU-111 (Sabizabulin) in the treatment of metastatic castration-resistant prostate cancer in patients who have failed prior treatment with at least one androgen receptor targeting agent as measured by radiographic progression-free survival.","other_id":"V3011102","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Single","intervention_model_description":"This randomized, open-label, active-control clinical study consists of two treatment arms:VERU-111 (Sabizabulin) treated group, and Control treated group. Subjects will be randomized in a 2:1 fashion.","sampling_method":"","gender":"Male","minimum_age":18,"maximum_age":100,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Provide informed consent.\r\n\r\n          -  Be able to communicate effectively with the study personnel.\r\n\r\n          -  Aged 18 years.\r\n\r\n          -  Histological or cytologic proof of adenocarcinoma of the prostate not including the\r\n             diagnosis of small cell carcinoma of the prostate of neuroendocrine pathology.\r\n\r\n          -  Radiographic evidence of metastatic disease at baseline by CT scan, or MRI and bone\r\n             scan, with confirmation of measurable disease by RECIST 1.1 and/or identifiable\r\n             discrete bone metastases by PCWG3.\r\n\r\n          -  Known castration resistant prostate cancer, defined according to PCWG3 criteria.\r\n\r\n          -  Have received at least one androgen receptor targeting agent (e.g. abiraterone,\r\n             enzalutamide, darolutamide, or apalutamide).\r\n\r\n          -  Subjects who have metastatic castration resistant prostate cancer that have maintained\r\n             ADT and have failed prior treatment with at least one androgen receptor targeting\r\n             agent (abiraterone,enzalutamide, darolutamide, or apalutamide) defined as:\r\n\r\n          -  Serum PSA progression of two consecutive increases in PSA over a previous reference\r\n             value within 6 months of first study treatment, each measurement at least 2 weeks\r\n             apart. Or\r\n\r\n          -  Documented bone lesions by the appearance of two or more new lesions on bone\r\n             scintigraphy or bi-dimensionally-measurable soft tissue metastatic lesion assessed by\r\n             CT or MRI.\r\n\r\n          -  Treatment with an alternative androgen receptor targeting agent is a reasonable next\r\n             line of therapy.\r\n\r\n          -  Absolute PSA 2.0 ng/ml at screening.\r\n\r\n          -  ECOG performance status <2.\r\n\r\n          -  Participants must have normal organ and bone marrow function measured within 30 days\r\n             prior to administration of study treatment as defined below:\r\n\r\n          -  Hemoglobin 9.0 g/dL with no blood transfusion in the past 30 days\r\n\r\n          -  Creatinine clearance 60 mL/min\r\n\r\n          -  Absolute neutrophil count (ANC) 1.5 x 109/L\r\n\r\n          -  Platelet count 100 x 109/L\r\n\r\n          -  Total bilirubin  upper limit of normal (ULN) (or <2.5 x ULN for patients with known\r\n             Gilberts disease)\r\n\r\n          -  Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase\r\n             (SGOT))/Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT))\r\n             2.5 x ULN. NOTE: Patients with elevations in bilirubin, AST, or ALT should be\r\n             thoroughly evaluated for the etiology of this abnormality prior to entry and patients\r\n             with evidence of viral infection should be excluded. Patients with chronic renal stent\r\n             and stable creatinine elevation can be included in the study with written\r\n             documentation from the PI.\r\n\r\n          -  Participants must have a life expectancy >3 months.\r\n\r\n          -  Subjects must agree to use acceptable methods of contraception:\r\n\r\n          -  If the study subject's partner could become pregnant, use acceptable methods of\r\n             contraception from the time of the first administration of study medication until\r\n             6months following administration of the last dose of study medication. Acceptable\r\n             methods of contraception are as follows: Condom with spermicidal\r\n             foam/gel/film/cream/suppository [i.e.,barrier method of contraception], surgical\r\n             sterilization (vasectomy with documentation of azospermia) and a barrier method\r\n             {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner\r\n             uses oral contraceptives (combination estrogen/progesterone pills), injectable\r\n             progesterone or subdermal implants and a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository).\r\n\r\n          -  If female partner of a study subject has undergone documented tubal ligation (female\r\n             sterilization), a barrier method (condom used with spermicidal\r\n             foam/gel/film/cream/suppository)should also be used.-If female partner of a study\r\n             subject has undergone documented placement of an intrauterine device (IUD) or\r\n             intrauterine system (IUS),a barrier method (condom with spermicidal\r\n             foam/gel/film/cream/suppository)should also be used.\r\n\r\n          -  Other than metastatic prostate cancer, no evidence (within 5 years) of prior\r\n             malignancies (except successfully treated basal cell or squamous cell carcinoma of the\r\n             skin or other cancers treated with curative intent >3 years prior).\r\n\r\n          -  Participants must agree to refrain from prolonged exposure to the sun or agree to use\r\n             at least SPF 50 on all exposed skin and protective clothing during prolonged sun\r\n             exposure throughout participation in this study and/or treatment with VERU- 111.\r\n\r\n          -  Subject is willing to comply with the requirements of the protocol through the end of\r\n             the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known hypersensitivity or allergy to colchicine.\r\n\r\n          -  Histologic identification of small cell carcinoma of the prostate or neuroendocrine\r\n             pathology in either biopsy or prostatectomy tissue.\r\n\r\n          -  A bone scan with evidence of superscan or superscan phenomenon, defined as:\r\n\r\n          -  Uptake throughout the axial skeleton and proximal appendicular skeleton, often\r\n             somewhat heterogeneous, or,\r\n\r\n          -  Symmetrically intense and diffuse radiotracer uptake in the skeleton with absent or\r\n             diminished visualization of the genitourinary system and soft tissues, or,\r\n\r\n          -  Defined in the bone scan report as a superscan or superscan phenomenon. NOTE: Medical\r\n             Monitor should be consulted prior to screening of a patient if a superscan or\r\n             superscan phenomenon is suspected or possible, but undetermined by any of the above\r\n             definitions.\r\n\r\n          -  Has received external-beam radiotherapy within the last 2 weeks prior to start of\r\n             study treatment.\r\n\r\n          -  Patients with a QT interval corrected by Fridericia's formula of >480 ms.\r\n\r\n          -  Patients receiving full dose warfarin therapy are not eligible for study.\r\n\r\n          -  Patients with prior history of a thromboembolic event within the last 6 months.\r\n\r\n          -  Participation in another clinical study with an investigational product during the\r\n             last 6 months prior to randomization into this study.\r\n\r\n          -  Patients should be excluded if they have had prior systemic treatment with prior\r\n             taxane chemotherapies (for greater than 2 cycles) for advanced prostate cancer.\r\n             Patient can have up to 2 cycles of prior taxane chemotherapy greater than one year\r\n             prior to randomization and remain eligible for inclusion in this study. Taxane\r\n             exposure in the adjuvant or neoadjuvant setting is allowed (maximum of 6 cycles).\r\n\r\n          -  Any treatment modalities involving major surgery within 4weeks prior to the start of\r\n             study treatment.\r\n\r\n          -  Patients are excluded if they have known brain metastases or leptomeningeal\r\n             metastases.\r\n\r\n          -  Patients should be excluded if they have a positive test for hepatitis B virus surface\r\n             antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating\r\n             acute or chronic infection.\r\n\r\n          -  Has imminent or established spinal cord compression based on clinical findings and/or\r\n             MRI.\r\n\r\n          -  Any other serious illness or medical condition that would, in the opinion of the\r\n             investigator, make this protocol unreasonably hazardous. Active infections discovered\r\n             during screening period must be treated and controlled before patient is dosed with\r\n             VERU-111.\r\n\r\n          -  Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)\r\n             caused by previous cancer therapy, excluding alopecia.\r\n\r\n          -  Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant\r\n             systemic disease or active, uncontrolled infection. Examples include, but are not\r\n             limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial\r\n             infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung\r\n             disease, or any psychiatric disorder that prohibits obtaining informed consent.\r\n\r\n          -  Total bilirubin levels > 1.5 x ULN (>2.5 x ULN in patients with known Gilbert's\r\n             disease).\r\n\r\n          -  AST and/or ALT levels >2.5xULN or AST and/or ALT levels >1.5xULN WITH concomitant\r\n             alkaline phosphatase levels >2.5xULN.\r\n      ","sponsor":"Veru Inc.","sponsor_type":"Industry","conditions":"Metastatic Castration-resistant Prostate Cancer|Androgen Resistant Prostatic Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: VERU-111","description":"Based on the safety and antitumor activity of VERU-111 in the Phase 1b/2 clinical study, VERU-111 is initiating this Phase 3 clinical study of VERU-111 for the treatment of metastatic castration resistant prostate cancer in patients who have failed prior treatment with at least one androgen receptor targeting agent"},{"intervention_type":"Drug","name":"Drug: Enzalutamide, Abiraterone, Darolutamide and Apalutamide","description":"Enzalutamide and abiraterone were chosen as active comparators are both are FDA approved for the treatment of metastatic castration resistant prostate cancer"}],"outcomes":[{"outcome_type":"primary","measure":"Efficacy of VERU-111 in the treatment of metastatic castration-resistant prostate cancer in patients who have failed prior treatment with at least one androgen receptor targeting agent","time_frame":"360 days","description":"Radiographic progression-free survival (rPFS) centrally read, which is death or tumor progression as defined by RECIST 1.1 (soft tissue) and PCWG3 (bone)."},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"360 days","description":"Overall survival (OS) will be an assessment of time from randomization into the study to all-cause mortality. The analysis will be performed similarly to the primary endpoint."}]}
{"nct_id":"NCT04739761","start_date":"2021-06-22","phase":"Phase 3","enrollment":500,"brief_title":"A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer","official_title":"An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12)","primary_completion_date":"2024-01-19","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-19","last_update":"2021-09-13","description":"This is open-label, multicenter, international study, assessing the efficacy and safety of Trastuzumab deruxtecan (T-DXd) in participants with or without brain metastasis (BMs), with previously-treated advanced/metastatic HER2-positive breast cancer whose disease has progressed on prior anti-HER2-based regimens and who received no more than 2 lines/regimens of therapy in the metastatic setting (excluding tucatinib).","other_id":"D9673C00007","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion:\r\n\r\n          -  Participants should have pathologically documented breast cancer that is:\r\n             unresectable/advanced or metastatic; confirmed HER2-positive status expression as\r\n             determined according to American Society of Clinical Oncology/College of American\r\n             Pathologists guidelines\r\n\r\n          -  Participant must have either: no evidence of BM, or untreated BM on screening contrast\r\n             brain magnetic resonance imaging/ computed tomography (MRI/CT) scan, not needing\r\n             immediate local therapy or previously-treated stable or progressing BM\r\n\r\n          -  Participants with BMs must be neurologically stable\r\n\r\n          -  For participants requiring radiotherapy due to BMs, there should be an adequate\r\n             washout period before day of first dosing:\r\n\r\n          -   7 days since stereotactic radiosurgery or gamma knife\r\n\r\n          -   21 days since whole brain radiotherapy\r\n\r\n          -  Eastern Cooperative Oncology Group performance status 0-1\r\n\r\n          -  Previous breast cancer treatment: radiologic or objective evidence of disease\r\n             progression on trastuzumab, pertuzumab, or trastuzumab emtansine and no more than 2\r\n             lines/regimens of therapy in the metastatic setting\r\n\r\n          -  Participant with the following measurable: at least 1 lesion that can be accurately\r\n             measured at baseline as  10 mm in the longest diameter with CT or MRI and is suitable\r\n             for accurate repeated measurements; or following Non-measurable diseases:\r\n             Non-measurable, bone-only disease that can be assessed by CT or MRI or X-Ray. Lytic or\r\n             mixed lytic bone lesions that can be assessed by CT or MRI or X-ray in the absence of\r\n             measurable disease as defined above is acceptable; Participants with\r\n             sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not\r\n             eligible; and Non-measurable CNS disease (Cohort 2 only)\r\n\r\n          -  Adequate organ and bone marrow function within 14 days before the day of first dosing\r\n             as defined in the protocol\r\n\r\n          -  left ventricular ejection fraction  50% within 28 days before enrollment\r\n\r\n          -  Negative pregnancy test (serum) for women of childbearing potential\r\n\r\n        Exclusion Criteria\r\n\r\n          -  Known or suspected leptomeningeal disease\r\n\r\n          -  Prior exposure to tucatinib treatment\r\n\r\n          -  Refractory nausea and vomiting, chronic gastrointestinal disease, or previous\r\n             significant bowel resection that would preclude adequate absorption, distribution,\r\n             metabolism, or excretion of T-DXd\r\n\r\n          -  History of another primary malignancy except for malignancy treated with curative\r\n             intent with no known active disease within 3 years before the first dose of study\r\n             intervention and of low potential risk for recurrence\r\n\r\n          -  Persistent toxicities (Common Terminology Criteria for Adverse Events Grade >1) caused\r\n             by previous anticancer therapy, excluding alopecia\r\n\r\n          -  Based on screening contrast brain MRI/CT scan, participants must not have any of the\r\n             following: any untreated brain lesions > 2.0 cm in size; ongoing use of systemic\r\n             corticosteroids for control of symptoms of BMs; any brain lesion thought to require\r\n             immediate local therapy; have poorly controlled (> 1/week) generalized or complex\r\n             partial seizures, or manifest neurologic progression due to BMs not withstanding\r\n             CNS-directed therapy\r\n\r\n          -  Has spinal cord compression\r\n\r\n          -  Known active hepatitis B or C infection, such as those with serologic evidence of\r\n             viral infection within 28 days of Cycle 1 Day 1. Participants with past or resolved\r\n             hepatitis B virus infection are eligible, if negative for hepatitis B surface antigen\r\n             and positive for anti-hepatitis B core antigen\r\n\r\n          -  Participants positive for hepatitis C virus (HCV) antibody are eligible only if\r\n             polymerase chain reaction is negative for HCV RNA\r\n\r\n          -  Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\r\n\r\n          -  Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd\r\n\r\n          -  Participants with a medical history of myocardial infarction within 6 months before\r\n             screening, symptomatic congestive heart failure (New York Heart Association Class II\r\n             to IV)\r\n\r\n          -  History of (non-infectious) ILD/pneumonitis that required steroids, has current\r\n             ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at\r\n             screening\r\n\r\n          -  Lung-specific intercurrent clinically significant illnesses and any autoimmune,\r\n             connective tissue or inflammatory disorders\r\n\r\n          -  Prior exposure, without adequate treatment washout period before the day of first\r\n             dosing, to chloroquine/hydroxychloroquine: < 14 days\r\n\r\n          -  Anticancer chemotherapy: immunotherapy (non-antibody-based therapy), retinoid therapy,\r\n             hormonal therapy: < 3 weeks\r\n\r\n          -  < 6 weeks for nitrosoureas or mitomycin\r\n\r\n          -  < 1 week for tyrosine kinase inhibitor (TKIs) approved for the treatment of non-small\r\n             cell lung cancer - baseline CT scan must be completed after discontinuation of TKI\r\n\r\n          -  Antibody-based anticancer therapy: < 4 weeks\r\n\r\n          -  Any concurrent anticancer treatment. Concurrent use of hormonal therapy for noncancer-\r\n             related conditions is allowed\r\n\r\n          -  Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide\r\n             field of radiation, radiation to the chest, or to more than 30% of the bone marrow\r\n             within 4 weeks before the first dose of study intervention\r\n\r\n          -  Participants with prior exposure to immunosuppressive medication within 14 days prior\r\n             to first study dose\r\n\r\n          -  Participants with a known hypersensitivity to study intervention or any of the\r\n             excipients of the product or other monoclonal antibodies\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab Deruxtecan","description":"Participants will receive T-DXd administered using an IV bag containing 5% (w/v) dextrose injection infusion solution."}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1)","time_frame":"From screening until progression of disease [PD] (Up to 2.5 Years)","description":"To describe the overall treatment effect of T- DXd in HER2-positive metastatic breast cancer (MBC) participants without baseline BM. An ORR is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by independent central review (ICR) per RECIST 1.1."},{"outcome_type":"primary","measure":"Progression-free Survival (PFS) in Participants with BM at Baseline (Cohort 2)","time_frame":"From screening until PD (Up to 2.5 Years)","description":"To describe the overall treatment effect of T- DXd in HER2-positive MBC participants with baseline BM. The PFS will be defined as the time from the date of the first dose of study intervention until the date of objective PD per RECIST 1.1 as assessed by ICR or death."},{"outcome_type":"secondary","measure":"Overall Survival (OS) in Months","time_frame":"At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. An OS is defined as the time from the date of the first dose of study intervention until death due to any cause."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Screening Day (-28 days) until end-of-treatment (EOT) (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. The DoR will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by ICR or death due to any cause."},{"outcome_type":"secondary","measure":"Time to Progression","time_frame":"Screening Day (-28 days) until PD (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. Time to progression by RECIST 1.1 per ICR is defined as the time from the date of the first dose of study intervention to the date of documented disease progression."},{"outcome_type":"secondary","measure":"Duration of Treatment on Subsequent Lines of Therapy","time_frame":"At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. Duration of treatment on subsequent therapy will be defined as the time from the date of first dose of a subsequent therapy until date of the last dose of that therapy."},{"outcome_type":"secondary","measure":"Time to Second Progression or Death (PFS2)","time_frame":"At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. The PFS2 is defined as time from the first dose of study intervention to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death."},{"outcome_type":"secondary","measure":"Incidence of new Symptomatic Central Nervous System (CNS) Metastasis During Treatment in Participants without BM at Baseline (Cohort 1)","time_frame":"At Screening day (-28 days), Cycle 1 (15 days ± 2 days) Day 1 and Cycle 3 (15 days ± 2 days) Day 1 and thereafter every 3 subsequent cycles (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression of BM in participants without baseline BM using additional efficacy measurements."},{"outcome_type":"secondary","measure":"Time to Next Progression (CNS or extracranial) or Death","time_frame":"Screening Day (-28 days) until next PD (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression (central nervous system [CNS] progression) of BM in participants without baseline BM using additional efficacy measurements. The time to next progression is defined as the time from the date of the first documented isolated CNS progression to the date of the next documented disease progression (CNS or extracranial) per RECIST 1.1 or death, and will be summarized descriptively in participants who develop isolated CNS progression, receive local therapy, and continue on protocol therapy."},{"outcome_type":"secondary","measure":"Site (CNS vs extracranial vs both) of Next Progression","time_frame":"Screening Day (-28 days) until next PD (Approximately 2.5 Years)","description":"To describe the treatment effect on the development and progression (CNS progression) of BM in participants without baseline BM using additional efficacy measurements. Site of next progression will be summarized descriptively in participants who develop isolated CNS progression, receive local therapy, continue on protocol therapy, and have a subsequent documented disease progression (CNS or extracranial) per RECIST 1.1."},{"outcome_type":"secondary","measure":"Objective Response Rate in Participants with BM at Baseline (Cohort 2)","time_frame":"From screening until PD (Up to 2.5 Years)","description":"To describe efficacy in participants with stable or untreated BM. An ORR will be evaluated by RECIST 1.1 per ICR."},{"outcome_type":"secondary","measure":"Central Nervous System Progression-free Survival in Participants with BM at Baseline (Cohort 2)","time_frame":"At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years)","description":"To describe efficacy in participants with stable or untreated BM. The CNS PFS is defined as time from the first dose of study intervention to CNS progression per CNS RECIST 1.1 or death resulting from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Time to new CNS Lesions in Participants with BM at Baseline (Cohort 2)","time_frame":"Screening Day (-28 days) until EOT (Approximately 2.5 Years)","description":"To describe efficacy in participants with stable or untreated BM. The time to new CNS lesions is defined as the time from the date of the first dose of study intervention to the date of documented new CNS lesions."},{"outcome_type":"secondary","measure":"Central Nervous System Objective Response Rate in Participants with BM at Baseline by ICR (Cohort 2)","time_frame":"Screening Day (-28 days) until EOT (Approximately 2.5 Years)","description":"To describe efficacy in participants with stable or untreated BM. The CNS ORR is defined as the proportion of participants with measurable BM at baseline who have a confirmed CR or confirmed PR of brain lesions, as determined by ICR per CNS RECIST 1.1."},{"outcome_type":"secondary","measure":"Central Nervous System Duration of Response in Participants with BM at Baseline (Cohort 2)","time_frame":"Screening Day (-28 days) until EOT (Approximately 2.5 Years)","description":"To describe efficacy in participants with stable or untreated BM. The CNS DoR will be defined as the time from the date of first documented confirmed CNS response until date of documented CNS progression per CNS RECIST 1.1 as assessed by ICR or death due to any cause."},{"outcome_type":"secondary","measure":"European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)","time_frame":"Cycle 1 (15 days ± 2 days) Day 1, thereafter every 3 weeks (q3w) until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years)","description":"To describe the effect of T-DXd on symptoms, functioning, and health-related quality of life (HRQoL) in HER2+ MBC participants with or without baseline BM."},{"outcome_type":"secondary","measure":"Neurologic Assessment in Neuro-Oncology Scale","time_frame":"Cycle 1 (15 days ± 2 days [Day 1]), Cycle 2 (15 days ± 2 days) Day 1, Cycle 3 (15 days ± 2 days) Day 1, Cycle 4 (15 days ± 2 days) Day 1 thereafter subsequent Cycles until PD and at EOT visit (Approximately 2.5 Years)","description":"To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM."},{"outcome_type":"secondary","measure":"Cognitive Functions Tests","time_frame":"Cycle 1 (15 days ± 2 days) Day 1, thereafter q12w and at EOT visit (Approximately 2.5 Years)","description":"To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM."},{"outcome_type":"secondary","measure":"MD Anderson Symptom Inventory Brain Tumor-specific Items","time_frame":"Cycle 1 (15 days ± 2 days) Day 1, thereafter q3w until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years)","description":"To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM."},{"outcome_type":"secondary","measure":"St. George's Respiratory Questionnaire - idiopathic pulmonary fibrosis version in Participants with Interstitial Lung Disease (ILD)/Pneumonitis","time_frame":"After diagnosis of ILD/pneumonitis and thereafter once weekly until EOT and safety F/U (40+7 days after last dose) (Approximately 2.5 Years)","description":"To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM."},{"outcome_type":"secondary","measure":"Number of Participants with Adverse Events","time_frame":"Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years)","description":"To describe the safety profile of T-DXd."},{"outcome_type":"secondary","measure":"Number of Participants with Investigator-assessed ILD/Pneumonitis or Rate of Investigator-assessed ILD/Pneumonitis","time_frame":"Cycle 1 (15 days ± 2 days) Day 1 until C4 (15 days ± 2 days) Day 1 and thereafter subsequent cycles until PD (Approximately 2.5 Years)","description":"To describe the safety profile of T-DXd."},{"outcome_type":"secondary","measure":"Number of Participants with Adverse Events with BM at Baseline","time_frame":"Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years)","description":"To describe the safety profile of T-DXd."}]}
{"nct_id":"NCT04802759","start_date":"2021-06-20","phase":"Phase 1/Phase 2","enrollment":255,"brief_title":"A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer","official_title":"A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS- BREAST CANCER)","primary_completion_date":"2026-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-04-30","last_update":"2021-09-05","description":"This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The current cohort (Cohort 1) will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor (ER)-positive breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population.","other_id":"CO42867","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Inclusion Criteria for Cohort 1:\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1\r\n\r\n          -  Documented estrogen receptor-positive (ER+) tumor\r\n\r\n          -  Patients for whom endocrine therapy is recommended and treatment with cytotoxic\r\n             chemotherapy is not indicated at time of entry into the study, as per national or\r\n             local treatment guidelines\r\n\r\n          -  Radiologic/objective evidence of recurrence or progression after the most recent\r\n             systemic therapy for breast cancer\r\n\r\n          -  Disease progression during or after first- or second-line hormonal therapy for locally\r\n             advanced or metastatic disease (note: at least one line of therapy must have contained\r\n             a CDK4/6i administered for a minimum of 8 weeks prior to disease progression.)\r\n\r\n          -  Postmenopausal status for women\r\n\r\n          -  Life expectancy 3 months\r\n\r\n          -  Availability of a representative tumor specimen that is suitable for evaluation of\r\n             Ki67, and/or additional biomarkers via central testing\r\n\r\n          -  Prior fulvestrant therapy is allowed\r\n\r\n          -  Measurable disease\r\n\r\n          -  Adequate hematologic and end-organ function\r\n\r\n          -  For patients receiving therapeutic anticoagulation: stable anticoagulant regimen\r\n\r\n        Exclusion Criteria:\r\n\r\n        General Exclusion Criteria for Cohort 1:\r\n\r\n          -  Known HER2-positive breast cancer\r\n\r\n          -  Prior treatment with cytotoxic chemotherapy for metastatic breast cancer\r\n\r\n          -  Concurrent hormone replacement therapy\r\n\r\n          -  Prior treatment with any of the protocol-specified study treatments\r\n\r\n          -  Treatment with investigational therapy within 28 days prior to initiation of study\r\n             treatment\r\n\r\n          -  Systemic treatment for ER+ breast cancer within 2 weeks of Cycle 1, Day 1 or 5\r\n             half-lives of the drug prior to Cycle 1, Day 1\r\n\r\n          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or\r\n             better, with the exception of alopecia of any grade and Grade 2 peripheral neuropathy\r\n\r\n          -  Prior allogeneic stem cell or solid organ transplantation\r\n\r\n          -  Major surgical procedure other than for diagnosis within 4 weeks prior to initiation\r\n             of study treatment or anticipation of need for a major surgical procedure during the\r\n             course of the study\r\n\r\n          -  History of malignancy other than breast cancer within 2 years prior to screening, with\r\n             the exception of those with a negligible risk of metastasis or death\r\n\r\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent\r\n             drainage procedures\r\n\r\n          -  Uncontrolled tumor-related pain\r\n\r\n          -  Uncontrolled or symptomatic hypercalcemia\r\n\r\n          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)\r\n             metastases\r\n\r\n          -  History of leptomeningeal disease\r\n\r\n          -  Active tuberculosis\r\n\r\n          -  Severe infection within 4 weeks prior to initiation of study treatment\r\n\r\n          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation\r\n             of study treatment\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced\r\n             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening\r\n             chest computed tomography scan\r\n\r\n          -  Active cardiac disease or history of cardiac dysfunction\r\n\r\n          -  Positive HIV test at screening or at any time prior to screening\r\n\r\n          -  Active Hepatitis B or Hepatitis C virus infection\r\n\r\n          -  Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major\r\n             upper gastrointestinal (GI) surgery, including gastric resection, potentially\r\n             affecting enteral absorption\r\n\r\n          -  Known allergy or hypersensitivity to any of the study drugs or any of their excipients\r\n\r\n        Giredestrant + Ipatasertib Arm Exclusion Criteria:\r\n\r\n          -  Prior treatment with an Akt inhibitor\r\n\r\n          -  Grade 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia\r\n\r\n          -  History of Type 1 or Type 2 diabetes mellitus requiring insulin\r\n\r\n          -  Congenital long QT syndrome or screening QTcF >480 milliseconds\r\n\r\n          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically\r\n             significant in the investigator's opinion\r\n\r\n          -  Treatment with strong CYP3A4 inducers and inhibitors within 4 weeks or 5\r\n             drug-elimination half-lives, whichever is longer, prior to initiation of study drug\r\n\r\n        Giredestrant + Abemaciclib Arm Exclusion Criteria:\r\n\r\n          -  Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy\r\n\r\n          -  History of major surgical resection involving the stomach or small bowel, or a\r\n             preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea\r\n\r\n          -  History of syncope of cardiovascular etiology, ventricular arrhythmia, or sudden\r\n             cardiac arrest\r\n\r\n        Giredestrant + Inavolisib Arm Exclusion Criteria:\r\n\r\n          -  Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of\r\n             action is to inhibit the PI3K/Akt/mTOR pathway\r\n\r\n          -  Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or\r\n             any history of Type 1 diabetes\r\n\r\n          -  Fasting glucose 126 mg/dL or 7.0 mmol/L and HbA1c 5.7%\r\n\r\n          -  Any concurrent ocular or intraocular condition that, in the opinion of the\r\n             investigator, would require medical or surgical intervention during the study period\r\n             to prevent or treat vision loss that might result from that condition\r\n\r\n          -  Active inflammatory or infectious conditions in either eye or history of idiopathic or\r\n             autoimmune-associated uveitis in either eye\r\n\r\n          -  Symptomatic active lung disease, including pneumonitis\r\n\r\n          -  Inability to confirm biomarker eligibility based on valid results from either central\r\n             testing of blood or local testing of blood or tumor tissue that documents one of the\r\n             protocol-defined PIK3CA mutations\r\n\r\n        Giredestrant + Ribociclib Arm Exclusion Criteria:\r\n\r\n          -  Currently receiving any of the following substances within 7 days before\r\n             randomization: concomitant medications, herbal supplements, and/or fruits that are\r\n             known as strong inhibitors or inducers of CYP3A4/5 or medications that have a narrow\r\n             therapeutic window and are predominantly metabolized through CYP3A4/5\r\n\r\n          -  Currently receiving or has received systemic corticosteroids 2 weeks prior to\r\n             starting trial treatment\r\n\r\n          -  Impairment of GI function or GI disease that may significantly alter the absorption of\r\n             the oral trial treatments\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Giredestrant","description":"30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression"},{"intervention_type":"Drug","name":"Drug: Abemaciclib","description":"150 mg orally twice a day during each 28-day cycle until unacceptable toxicity or disease progression"},{"intervention_type":"Drug","name":"Drug: Ipatasertib","description":"400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression"},{"intervention_type":"Drug","name":"Drug: Inavolisib","description":"9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression"},{"intervention_type":"Drug","name":"Drug: Ribociclib","description":"600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression"},{"intervention_type":"Drug","name":"Drug: Everolimus","description":"10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression"}],"outcomes":[{"outcome_type":"primary","measure":"Plasma Concentration of Ipatasertib at Specified Timepoints","time_frame":"Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days)"},{"outcome_type":"primary","measure":"Percentage of Participants with Objective Response, Defined as a Complete or Partial Response, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)","time_frame":"From Baseline until disease progression (up to 6 years)"},{"outcome_type":"primary","measure":"Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)","time_frame":"From Baseline until 30 days after the last dose of study drug (up to 6 years)"},{"outcome_type":"primary","measure":"Plasma Concentration of Giredestrant at Specified Timepoints","time_frame":"Day 1 of Cycles 1, 2, 4, 8, and 16 (each cycle is 28 days), and at treatment discontinuation visit (within 30 days after last dose)"},{"outcome_type":"primary","measure":"Plasma Concentration of Abemaciclib at Specified Timepoints","time_frame":"Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days), and at treatment discontinuation visit (within 30 days after last dose)"},{"outcome_type":"primary","measure":"Plasma Concentration of Inavolisib at Specified Timepoints","time_frame":"Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days)"},{"outcome_type":"primary","measure":"Plasma Concentration of Ribociclib at Specified Timepoints","time_frame":"Days 1 and 15 of Cycle 1; Day 1 of Cycle 2 (each cycle is 28 days)"},{"outcome_type":"primary","measure":"Blood Concentration of Everolimus at Specified Timepoints","time_frame":"Days 1 and 15 of Cycle 1; Day 1 of Cycle 2 (each cycle is 28 days)"},{"outcome_type":"secondary","measure":"Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1","time_frame":"From randomization to the date of the first recorded occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)"},{"outcome_type":"secondary","measure":"Disease Control Rate, Defined as the Percentage of Participants with Stable Disease for ≥12 Weeks or a Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1","time_frame":"From Baseline until disease progression (up to 6 years)"},{"outcome_type":"secondary","measure":"Clinical Benefit Rate, Defined as the Percentage of Participants with Stable Disease for ≥24 Weeks or with Confirmed Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1","time_frame":"From Baseline until disease progression (up to 6 years)"},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"From randomization to death from any cause (up to 6 years)"},{"outcome_type":"secondary","measure":"Duration of Response, as Determined by the Investigator According to RECIST v1.1","time_frame":"From first occurrence of a document objective response to the first date of recorded disease progression or death from any cause, whichever occurs first (up to 6 years)"}]}
{"nct_id":"NCT04895358","start_date":"2021-06-18","phase":"Phase 3","enrollment":800,"brief_title":"Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Locally Recurrent Inoperable or Metastatic Breast Cancer (MK-3475-B49/KEYNOTE-B49)","official_title":"A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for the Treatment of Chemotherapy-Candidate Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Locally Recurrent Inoperable or Metastatic Breast Cancer (KEYNOTE-B49)","primary_completion_date":"2027-10-21","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-10-21","last_update":"2021-09-16","description":"The safety and efficacy of pembrolizumab plus the investigator's choice of chemotherapy will be assessed compared to placebo plus the investigator's choice of chemotherapy in the treatment of chemotherapy-candidate hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally recurrent inoperable or metastatic breast cancer. The primary hypotheses are that the combination of pembrolizumab and chemotherapy is superior to placebo and chemotherapy in regards to Progression-Free Survival (PFS) or overall survival (OS) in participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) 1 and 10.","other_id":"3475-B49","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has locally recurrent inoperable or metastatic HR+/HER2- breast cancer, which has not\r\n             been previously treated with cytotoxic chemotherapy in the noncurative setting\r\n\r\n          -  Has progressed on 2 or more lines of endocrine therapy for metastatic\r\n             HR+/HER2-disease, with at least 1 given in combination with a Cyclin-dependent kinase\r\n             4/6 (CDK4/6) inhibitor OR\r\n\r\n          -  Has progressed on 1 line of endocrine therapy for metastatic HR+/HER2- disease and had\r\n             a relapse within 24 months of definitive surgery for primary tumor while on adjuvant\r\n             endocrine therapy. Prior treatment with a CDK4/6 inhibitor (in the metastatic and/or\r\n             adjuvant setting) is required OR\r\n\r\n          -  If no prior treatment with a CDK 4/6 inhibitor, participants must have progressed\r\n             within 6 months of starting 1 line of endocrine therapy for metastatic disease and had\r\n             a relapse within 24 months of definitive surgery for primary tumor and while on\r\n             adjuvant endocrine therapy\r\n\r\n          -  Has presented a documented progression (confirmed by scans per RECIST 1.1 as assessed\r\n             by the investigator and/or histology [biopsy or cytology] for participants presenting\r\n             with new metastatic lesions) during or after the last administered endocrine therapy\r\n             prior to entering the study\r\n\r\n          -  Is a chemotherapy candidate that meets the criteria specified in the protocol\r\n\r\n          -  Provides a new or the last obtained core biopsy, preferably consisting of multiple\r\n             cores, taken from a locally recurrent or a distant (metastatic) lesion not previously\r\n             irradiated\r\n\r\n          -  Has centrally confirmed PD-L1 CPS 1 and HR+ (estrogen receptor [ER] and/or\r\n             progesterone receptor [PgR]) /HER2- breast cancer as defined by the most recent\r\n             American Society of Clinical Oncology (ASCO)/(College of American Pathologists) CAP\r\n             guidelines on most recent tumor biopsy\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as\r\n             assessed within 7 days prior to the first dose of study treatment\r\n\r\n          -  Has adequate organ function within 10 days prior to the start of study\r\n\r\n          -  Male participants must agree to the following during the treatment period and for at\r\n             least 6 months after the last dose of chemotherapy: refrain from donating sperm PLUS\r\n             either be abstinent from heterosexual intercourse as their preferred and usual\r\n             lifestyle or use contraception and agree to use a male condom plus partner use of an\r\n             additional contraceptive\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant or\r\n             breastfeeding, and at least one of the following conditions applies: is not a woman of\r\n             childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective\r\n             contraceptive method during the treatment period and for at least 120 days after the\r\n             last dose of pembrolizumab and 180 days after the last dose of chemotherapy (whichever\r\n             occurs last), AND agrees not to donate eggs (ova, oocytes) to others or freeze/store\r\n             for her own use for the purpose of reproduction during this period\r\n\r\n          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within\r\n             24 hours for urine or within 72 hours for serum before the first dose of study\r\n             intervention\r\n\r\n          -  Has measurable disease per RECIST 1.1 as assessed by the local site\r\n             investigator/radiologist\r\n\r\n          -  If receiving bone resorptive therapy, including but not limited to bisphosphonates or\r\n             denosumab, has been receiving stable doses for 4 weeks prior to the date of\r\n             randomization\r\n\r\n          -  Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they\r\n             have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks prior to\r\n             the first dose of study intervention and have undetectable HBV viral load prior to\r\n             randomization\r\n\r\n          -  Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV\r\n             viral load is undetectable at screening\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has breast cancer amenable to treatment with curative intent\r\n\r\n          -  Has a history or current evidence of any condition (e.g., transfusion-dependent anemia\r\n             or thrombocytopenia), therapy, or laboratory abnormality that is specifically\r\n             contraindicated per the current locally-approved labeling, that might confound the\r\n             results of the study, interfere with the participant's involvement for the full\r\n             duration of the study, or is not in the best interest of the participant to be\r\n             involved, in the opinion of the treating investigator\r\n\r\n          -  Has significant cardiac disease, such as: history of myocardial infarction, acute\r\n             coronary syndrome, coronary angioplasty/stenting/bypass within the last 6 months,\r\n             congestive heart failure (CHF) New York Heart association (NYHA) Class II-IV, or\r\n             history of CHF NYHA Class III or IV\r\n\r\n          -  Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into\r\n             life-threatening complications, such as lymphangitic lung metastases, bone marrow\r\n             replacement, carcinomatous meningitis, significant symptomatic liver metastases,\r\n             shortness of breath requiring supplemental oxygen, symptomatic pleural effusion\r\n             requiring supplemental oxygen, symptomatic pericardial effusion, symptomatic\r\n             peritoneal carcinomatosis, or the need to achieve rapid symptom control\r\n\r\n          -  Has skin only disease\r\n\r\n          -  Has a known germline breast cancer (BRCA) mutation (deleterious or suspected\r\n             deleterious) and has not received previous treatment with poly ADP-ribose polymerase\r\n             (PARP) inhibition\r\n\r\n          -  Has received prior chemotherapy for locally recurrent inoperable or metastatic breast\r\n             cancer\r\n\r\n          -  Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti-\r\n             programmed cell death ligand 1 (PD-L1), or anti- programmed cell death ligand 2\r\n             (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell\r\n             receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)\r\n\r\n          -  Has received prior systemic anticancer therapy with other investigational agents\r\n             within 4 weeks prior to randomization\r\n\r\n          -  Has received palliative radiotherapy prior to start of study intervention and has not\r\n             recovered from all radiation-related toxicities and/or requires corticosteroids,\r\n             and/or has radiation pneumonitis\r\n\r\n          -  Has received a live or live attenuated vaccine within 30 days prior to the first dose\r\n             of study intervention- any licensed COVID-19 mRNA, adenoviral, or inactivated vaccines\r\n             are allowed\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks prior to the first dose of\r\n             study intervention\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior the first dose of study drug\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years with the exception of basal cell carcinoma of the skin,\r\n             squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma,\r\n             cervical cancer in situ) that have undergone potentially curative therapy\r\n\r\n          -  Has known active central nervous system (CNS) metastases\r\n\r\n          -  Has diagnosed carcinomatous meningitis\r\n\r\n          -  Has severe hypersensitivity to pembrolizumab and/or any of its excipients or has any\r\n             hypersensitivity to the planned chemotherapy agent (paclitaxel, nab-paclitaxel,\r\n             liposomal doxorubicin, or capecitabine) and/or any of their excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n          -  Has a history of (noninfectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known history of Human Immunodeficiency Virus (HIV) infection\r\n\r\n          -  Has a known COVID-19 infection (symptomatic or asymptomatic)\r\n\r\n          -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)\r\n\r\n          -  Has a known psychiatric or substance abuse disorder including alcohol or drug\r\n             dependency that would interfere with the participant's ability to cooperate with the\r\n             requirements of the study\r\n\r\n          -  Is breastfeeding or expecting to conceive or father children within the projected\r\n             duration of the study, starting with the screening visit through 180 days (or longer\r\n             as specified by local institutional guidelines) after the last dose of study treatment\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Breast Neoplasms","interventions":[{"intervention_type":"Biological","name":"Biological: pembrolizumab","description":"Intravenous (IV) infusion"},{"intervention_type":"Drug","name":"Drug: paclitaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: nab-paclitaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: liposomal doxorubicin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: capecitabine","description":"oral administration"},{"intervention_type":"Drug","name":"Drug: normal saline","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: dextrose","description":"IV infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 33 months","description":"PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by BICR, will be presented."},{"outcome_type":"primary","measure":"Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1","time_frame":"Up to approximately 33 months","description":"PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by BICR, will be presented."},{"outcome_type":"primary","measure":"Overall Survival (OS) in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 75 months","description":"OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥10 will be presented."},{"outcome_type":"primary","measure":"OS in Participants With CPS ≥1","time_frame":"Up to approximately 75 months","description":"OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥1 will be presented."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 75 months","description":"PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by investigator, will be presented."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator in Participants With Combined Positive Score (CPS) ≥1","time_frame":"Up to approximately 75 months","description":"PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by investigator, will be presented."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 75 months","description":"ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥10 will be presented."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1","time_frame":"Up to approximately 75 months","description":"ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥1 will be presented."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 75 months","description":"DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥10 will be presented."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1","time_frame":"Up to approximately 75 months","description":"DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥1 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10","time_frame":"Up to approximately 75 months","description":"For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥10 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1","time_frame":"Up to approximately 75 months","description":"For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥1 will be presented."},{"outcome_type":"secondary","measure":"Change From Baseline in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; \"How would you rate your overall health during the past week?\") and Quality of Life (QoL; \"How would you rate your overall quality of life during the past week?\") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥10. A higher score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change From Baseline in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; \"How would you rate your overall health during the past week?\") and Quality of Life (QoL; \"How would you rate your overall quality of life during the past week?\") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥1. A higher score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change From Baseline in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function."},{"outcome_type":"secondary","measure":"Change From Baseline in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function."},{"outcome_type":"secondary","measure":"Change From Baseline in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function."},{"outcome_type":"secondary","measure":"Change From Baseline in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function."},{"outcome_type":"secondary","measure":"Change From Baseline in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change From Baseline in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change From Baseline in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question \"Have you had diarrhea?\" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change From Baseline in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Baseline and up to approximately 75 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question \"Have you had diarrhea?\" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1","time_frame":"Up to approximately 75 months","description":"TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Percentage of Participants who Experience an Adverse Event (AE)","time_frame":"Up to approximately 75 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience one or more adverse events will be presented."},{"outcome_type":"secondary","measure":"Percentage of Participants who Discontinue Study Drug due to an AE","time_frame":"Up to approximately 75 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an adverse event will be presented."}]}
{"nct_id":"NCT04866017","start_date":"2021-06-17","phase":"Phase 3","enrollment":900,"brief_title":"Tislelizumab Plus BGB-A1217 Versus Tislelizumab Versus Durvalumab When Co-administered With Concurrent Chemoradiotherapy (cCRT) in Lung Cancer","official_title":"Phase 3, Randomized, Open Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Plus Concurrent Chemoradiotherapy (cCRT) Followed by Ociperlimab Plus Tislelizumab or Tislelizumab Plus cCRT Followed by Tislelizumab Versus cCRT Followed by Durvalumab in Previously Untreated, Locally Advanced, Unresectable Non-Small Cell Lung Cancer","primary_completion_date":"2025-01-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-09-30","last_update":"2021-07-01","description":"The primary objectives of this study is to compare progression free survival (PFS) and complete response rate (CRR) between participants treated with Ociperlimab plus tislelizumab plus Concurrent Chemoradiotherapy (cCRT) followed by Ociperlimab plus tislelizumab versus participants treated with tislelizumab plus Concurrent Chemoradiotherapy (cCRT) followed by tislelizumab versus participants treated with cCRT followed by durvalumab in previously untreated, locally advanced, unresectable non-small cell lung cancer (LA NSCLC) The secondary objective of this study is to compare overall survival (OS) and PFS in programmed cell death protein ligand-1 (PD-L1) positive population between Arm A and C.","other_id":"BGB-A317-A1217-301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          1. Age  18 years on the day of signing the ICF (or the legal age of consent in the\r\n             jurisdiction in which the study is taking place).\r\n\r\n          2. Participant has newly diagnosed, histologically confirmed, locally advanced, Stage III\r\n             unresectable NSCLC.\r\n\r\n          3. Measurable disease as assessed by RECIST v1.1.\r\n\r\n          4. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1.\r\n\r\n          5. Patients must have adequate organ function\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          1. Any prior therapy for lung cancer, including but not limited to chemotherapy,\r\n             radiotherapy, targeted therapy, biologic therapy, or immunotherapy.\r\n\r\n          2. Any prior radiotherapy to the thorax, including radiotherapy to the esophagus,\r\n             mediastinum, or for breast cancer.\r\n\r\n          3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT or any other antibody\r\n             or drug specifically targeting T-cell costimulation or checkpoint pathways.\r\n\r\n          4. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation or ALK gene\r\n             translocation.\r\n\r\n          5. Active autoimmune diseases or history of autoimmune diseases that may relapse.\r\n\r\n          6. Any condition that required systemic treatment with either corticosteroids (> 10 mg\r\n             daily of prednisone or equivalent) or other immunosuppressive medication  14 days\r\n             before the first dose of study treatment.\r\n\r\n          7. Infection (including tuberculosis infection, etc) requiring systemic antibacterial,\r\n             antifungal or antiviral therapy within 14 days before the first dose of study\r\n             treatment.\r\n\r\n        NOTE: Other protocol Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Tislelizumab","description":"100 mg/10 mL. 200 mg Q3W administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Durvalumab","description":"120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL). 10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been approved by a local health authority)"},{"intervention_type":"Drug","name":"Drug: Chemotherapy","description":"Cisplatin, carboplatin, etoposide, paclitaxel, pemetrexed will be administered in accordance with the relevant local guidelines and/or prescribing information/summary of product characteristics"},{"intervention_type":"Drug","name":"Drug: Ociperlimab","description":"300 mg/15 mL. 900 mg Q3W administered by intravenous infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-Free Survival (PFS) in the Intent-to-treat (ITT) Analysis set as assessed by the Independent Review Committee (IRC)","time_frame":"Up to 16 months","description":"Time from the date of randomization to the date of first documentation of disease progression assessed"},{"outcome_type":"primary","measure":"Complete Response Rate (CRR) as assessed by the Independent Review Committee (IRC)","time_frame":"Up to 16 months","description":"defined as the proportion of patients who achieve a complete response (CR) per Repose Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v.1.1)"},{"outcome_type":"secondary","measure":"Overall Survival (OS) in ITT Set","time_frame":"Up to 16 months","description":"Time from the date of randomization until the date of death due to any cause"},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) in the PD-L1-Positive Analysis Set as assessed by the IRC","time_frame":"Up to 16 months","description":"Time from the date of randomization to the date of first documentation of disease progression assessed"},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR) in ITT Set","time_frame":"Up to 16 months","description":"Proportion of participants who achieve a complete response (CR) or partial response (PR)"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) in ITT Set","time_frame":"Up to 16 months","description":"Time from the first determination of a confirmed objective response"},{"outcome_type":"secondary","measure":"time to death or distant metastasis (TTDM) in the Intent-to-treat (ITT) Analysis set as assessed by the investigator","time_frame":"Up to 16 months","description":"Time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field"},{"outcome_type":"secondary","measure":"Number of participants experiencing Adverse Events (AEs)","time_frame":"Up to 16 months"},{"outcome_type":"secondary","measure":"Number of participants experiencing Serious Adverse Events (SAEs)","time_frame":"Up to 16 months"},{"outcome_type":"secondary","measure":"Health Related Quality of Life (HRQoL) in the ITT set as assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)","time_frame":"Up to 16 months","description":"The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 (\"Not at all\"), 2 (\"A little\"), 3 (\"Quite a bit\") and 4 (\"Very much\"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.\r\nThe EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 (\"very poor\") to 7 (\"excellent\"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome."},{"outcome_type":"secondary","measure":"Health Related Quality of Life (HRQoL) in the ITT set as assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)","time_frame":"Up to 16 months","description":"The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) A score of 1-4 will be administrated for each item in QLQ-LC13. The higher scores will indicate the worse outcomes."},{"outcome_type":"secondary","measure":"Health Related Quality of Life (HRQoL) in the ITT set as assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)","time_frame":"Up to 16 months","description":"EQ-5D-5L - Is the EuroQol 5D-5L a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state."},{"outcome_type":"secondary","measure":"Serum concentration of BGB-A1217","time_frame":"Up to 30 minutes postdose"},{"outcome_type":"secondary","measure":"Serum concentration of Tislelizumab","time_frame":"Up to 30 minutes postdose"},{"outcome_type":"secondary","measure":"Immunogenic responses to BGB-A1217 as assessed by the detection of anti-drug antibodies (ADAs)","time_frame":"Up to 16 months"},{"outcome_type":"secondary","measure":"Immunogenic responses to Tislelizumab as assessed by the detection of anti-drug antibodies (ADAs)","time_frame":"Up to 16 months"},{"outcome_type":"secondary","measure":"Evaluate PD-L1 and TIGIT expression in archival and/or fresh tumor tissues","time_frame":"Up to 16 months","description":"before study treatment or at disease progression/reoccurrence, and their association with clinical efficacy."},{"outcome_type":"secondary","measure":"Complete Response Rate (CRR) in the Intent-to-treat (ITT) Analysis set as assessed by the investigator","time_frame":"Up to 16 months","description":"defined as the proportion of patients who achieve a CR"}]}
{"nct_id":"NCT04906993","start_date":"2021-06-15","phase":"Phase 3","enrollment":440,"brief_title":"Camrelizumab Combined With Famitinib Malate for Treatment of Recurrent/Metastatic Cervical Cancer","official_title":"A Randomized, Open-Label, Controlled, Multi-Center Phase III Clinical Study of Camrelizumab Combined With Famitinib Malate Versus Platinum-based Chemotherapy in the Treatment of Recurrent/Metastatic Cervical Cancer","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-05-31","last_update":"2021-05-28","description":"This study is a randomized, open-label, controlled, multi-center Phase III clinical study, aimed to evaluate the efficacy and safety of camrelizumab combined with famitinib malate versus platinum-based chemotherapy in the treatment of recurrent/metastatic cervical cancer. All enrolled patients will be randomly divided into 2 groups and continuously treated until any event that meets the criteria for end of the clinical trial.","other_id":"SHR-1210-III-329","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"1:1 camrelizumab combined with famitinib malate platinum-based chemotherapy","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Female aged 18-75 years (including 18 and 75 years, calculated based on the signing\r\n             date of the informed consent)\r\n\r\n          2. Histopathologically confirmed recurrent/metastatic cervical squamous cell carcinoma\r\n             that cannot be radically treated by surgery, radiotherapy or chemoradiotherapy\r\n\r\n          3. No prior systemic anti-cancer therapy for recurrent/metastatic disease\r\n\r\n          4. According to RECIST v1.1 criteria, the patient must have at least one measurable\r\n             lesion\r\n\r\n          5. Able to normally swallow drug tablets\r\n\r\n          6. The organ function level is good\r\n\r\n          7. Willing to participate and able to comply with research programme requirements\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has any malignancy <5 years prior to study entry.\r\n\r\n          2. Known to have brain or meningeal metastasis\r\n\r\n          3. Known to have autoimmune disease\r\n\r\n          4. Received live vaccinations 4 weeks before randomization or during the study period\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: camrelizumab famitinib malate","description":"Camrelizumab intravenously ; Famitinib Orally"},{"intervention_type":"Drug","name":"Drug: platinum-based chemotherapy","description":"Physician's choice chemotherapy"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) assessed by the BIRC based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"primary","measure":"Overall survival (OS)","time_frame":"up to 3 years"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) assessed by the investigator based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) assessed based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) assessed based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Duration of response (DOR) assessed based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Time to response (TTR) assessed based on RECIST V1.1 criteria","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Time to treatment failure (TTF)","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) in subjects in the control group who receive camrelizumab after progression","time_frame":"up to 2 years"}]}
{"nct_id":"NCT04894825","start_date":"2021-06-11","phase":"Phase 1","enrollment":152,"brief_title":"Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China","official_title":"A Phase I, Multi-center, Open-label, Single-dose Escalation and Expansion, Dose Escalation and Expansion Combination With Chemotherapy Study Evaluating the Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China","primary_completion_date":"2023-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-30","last_update":"2021-08-18","description":"M108 is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. The aim of this phase I study is to establish safety and Tolerability of different Dosage regimen in patients With Advanced Unresectable Solid Tumors in China.","other_id":"M108-","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Written informed consent.\r\n\r\n          2. Advanced Unresectable solid tumors proven by histology\r\n\r\n          3. At least 1 measurable site of the disease according RECIST 1.1 criteria\r\n\r\n          4. ECOG performance status (PS) 0-1\r\n\r\n          5. Life expectancy > 3 months\r\n\r\n          6. Age  18 years and 75 years\r\n\r\n          7. Adequate haematological function; absolute neutrophil count 1.5 x 109/L; white blood\r\n             cell count 3.0 x 109/L; platelets 100 x 109/L; haemoglobin 9 g/dL.\r\n\r\n          8. Adequate coagulation function; international normalized ratio ( INR)  1.5 x upper\r\n             limit of normal (ULN), or activated partial thromboplastin time (APTT)  1.5 x ULN.\r\n\r\n          9. Adequate hepatic function; bilirubin 1.5 x ULN, aspartate aminotransferase (AST), and\r\n             alanine aminotransferase (ALT) 2.5 x ULN.\r\n\r\n         10. Adequate renal function; creatinine 1.5 x ULN, or reatinine clearance rate 60\r\n             mL/minute calculated.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Previous received or planned to be vaccinated with 2019-nCoV vaccine or other vaccines\r\n             within 3 months prior to the start of study treatment or during the study or within 3\r\n             months after the end of the study;\r\n\r\n          2. Previous radiotherapy within 4 weeks prior to the start of study treatment. (if\r\n             palliative radiotherapy was given to bone metastatic side peripherally and the patient\r\n             recovered from acute toxicity was allowed).\r\n\r\n          3. Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.\r\n\r\n          4. Previous major operation within 8 weeks prior to the start of study treatment.\r\n\r\n          5. Prior severe allergic reaction or intolerance to a monoclonal antibody, including\r\n             humanised or chimeric antibodies.\r\n\r\n          6. Symptomatic cerebral metastases.\r\n\r\n          7. Uncontrolled or severe illness.\r\n\r\n          8. Known human immunodeficiency virus infection or known symptomatic hepatitis\r\n\r\n          9. Other clinically significant disease which may have adversely affected the safe\r\n             delivery of treatment within this study\r\n      ","sponsor":"FutureGen Biopharmaceutical (Beijing) Co., Ltd","sponsor_type":"Industry","conditions":"Advanced Unresectable Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: M108","description":"Monotherapy: Accelerated titration method, IV infusion Q3W; Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles) Combined with chemotherapy: Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles)"},{"intervention_type":"Drug","name":"Drug: M108","description":"IV infusion Q3W. (21-day cycles)"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of adverse events","time_frame":"From enrollment until 28+7 days after the last dose","description":"defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)"},{"outcome_type":"primary","measure":"Maximum Tolerated Dose","time_frame":"21 days","description":"MTD"},{"outcome_type":"secondary","measure":"Maximum measured plasma concentration of M108","time_frame":"From enrollment until 28 days after the last dose","description":"Cmax"},{"outcome_type":"secondary","measure":"Time to maximum plasma concentration of M108","time_frame":"From enrollment until 28 days after the last dose","description":"Tmax"},{"outcome_type":"secondary","measure":"Half-life of M108","time_frame":"From enrollment until 28 days after the last dose","description":"T1/2"},{"outcome_type":"secondary","measure":"Immunogenicity profile of M108","time_frame":"From enrollment until 28 days after the last dose","description":"Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies(ADA)."},{"outcome_type":"secondary","measure":"Objective Response Rate","time_frame":"From first dose to disease progression , death or end of study，an average of 1 year","description":"ORR"},{"outcome_type":"secondary","measure":"Progression free survival","time_frame":"From first dose to disease progression , death or end of study，an average of 1 year","description":"PFS"}]}
{"nct_id":"NCT04676477","start_date":"2021-06-11","phase":"Phase 1","enrollment":252,"brief_title":"Patritumab Deruxtecan in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer","official_title":"A Phase 1 Open-Label Study of Patritumab Deruxtecan in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)","primary_completion_date":"2024-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-31","last_update":"2021-06-15","description":"This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety. The primary objectives: Dose Escalation: To assess the safety and tolerability of patritumab deruxtecan (U3-1402) and osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib, and to determine the recommended combination dose (RCD). Second-Line Dose Expansion Arm 1 and Arm 1b: To assess the preliminary antitumor activity of patritumab deruxtecan and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. Note: One or both of the study arms may open with one or two distinct dosing schedules. Second-Line Dose Expansion Arm 2: To assess the preliminary antitumor activity of patritumab deruxtecan monotherapy in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. First-Line Dose Expansion: To assess the safety and tolerability of patritumab deruxtecan and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation without prior systemic treatment for locally advanced or metastatic disease.","other_id":"U31402-A-U103","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Inclusion Criteria Specific to Dose Escalation and Second-Line Dose Expansion:\r\n\r\n          -  Documentation of EGFR exon 19 deletion or L858R mutation detected from tumor tissue\r\n\r\n          -  Must have received osimertinib for locally advanced or metastatic disease at a dose of\r\n             80 mg once daily (QD) for at least 6 weeks and must not miss more than two doses\r\n             during the 2 weeks prior to the first day of study treatment (Cycle 1, Day 1)\r\n\r\n          -  Must not have received any other prior systemic cancer therapies in the locally\r\n             advanced/metastatic setting\r\n\r\n          -  Has documentation of radiological disease progression following first-line treatment\r\n             with osimertinib in the locally advanced or metastatic setting\r\n\r\n        Inclusion Criteria Specific to First-line Dose Expansion:\r\n\r\n          -  The tumor tissue harbors one of the 2 common EGFR mutations occurring in NSCLC known\r\n             to be associated with EGFR-TKI sensitivity (exon 19 deletion or L858R) as assessed by\r\n             Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US]\r\n             sites), accredited (outside of the US), local laboratory or central laboratory. Only\r\n             tissue-based testing will be accepted.\r\n\r\n          -  Participants must have previously untreated locally advanced or metastatic NSCLC and\r\n             must be eligible to receive first-line treatment with osimertinib, according to the\r\n             judgment of the investigator. Prior adjuvant or neo-adjuvant therapy (chemotherapy,\r\n             radiotherapy, investigational agents; except with osimertinib) is permitted.\r\n\r\n        All Participants:\r\n\r\n        Participants must meet all criteria to be eligible for inclusion in this study:\r\n\r\n          -  Histologically or cytologically documented locally advanced or metastatic NSCLC not\r\n             amenable to curative surgery or radiation.\r\n\r\n          -  At least 1 measurable lesion as assessed by Investigator as per Response Evaluation\r\n             Criteria in Solid Tumors (RECIST v1.1)\r\n\r\n          -  Willing to provide required tumor tissue of sufficient quantity (as defined in the\r\n             laboratory manual) and contain adequate tumor tissue content (as confirmed by\r\n             hematoxylin and eosin (H&E) staining at central laboratory). Required tumor tissue can\r\n             be provided as either:\r\n\r\n               -  Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and\r\n                  amenable to core biopsy OR\r\n\r\n               -  Archival tissue collected from a biopsy performed within 3 months prior to\r\n                  signing of the tissue consent and since progression while on the most recent\r\n                  cancer therapy regimen.\r\n\r\n               -  On-study tumor biopsies are required for the first 15 participants in Dose\r\n                  Escalation.\r\n\r\n          -  Has adequate bone marrow reserve and organ function based on local laboratory data\r\n             within 14 days prior to Cycle 1, Day 1 (Dose Escalation and First-Line Dose Expansion)\r\n             or within 14 days prior to randomization (Second-Line Dose Expansion):\r\n\r\n               -  Platelet count: 100 000/mm^3 or 100  10^9/L (platelet transfusions are not\r\n                  allowed up to 14 days prior to Cycle 1, Day 1 to meet eligibility)\r\n\r\n               -  Hemoglobin: 9.0 g/dL (transfusion and/or growth factor support is allowed)\r\n\r\n               -  Absolute neutrophil count ; 1500/mm^3 or 1.5  10^9/L\r\n\r\n               -  Serum creatinine (SCr) OR creatinine clearance (CrCl): SCr 1.5  ULN, OR CrCl\r\n                  30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl;\r\n                  confirmation of CrCl is only required when creatinine is >1.5  ULN\r\n\r\n          -  Aspartate aminotransferase/ alanine aminotransferase: 3  ULN (if liver metastases\r\n             are present, 5  ULN)\r\n\r\n          -  Total bilirubin: 1.5  ULN if no liver metastases (<3  ULN in the presence of\r\n             documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases)\r\n\r\n          -  Serum albumin ; 2.5 g/dL\r\n\r\n          -  Prothrombin time (PT) or PT-international normalized ratio (INR) and Activated partial\r\n             thromboplastin time (aPTT) / Partial thromboplastin time (PTT): 1.5  ULN, except for\r\n             subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy,\r\n             who must have PT-INR within therapeutic range as deemed appropriate by the\r\n             Investigator.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Any previous histologic or cytologic evidence of small cell OR combined small\r\n             cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.\r\n\r\n          -  Any history of interstitial lung disease (including pulmonary fibrosis or radiation\r\n             pneumonitis), has current interstitial lung disease (ILD), or is suspected to have\r\n             such disease by imaging during screening.\r\n\r\n          -  Clinically severe pulmonary compromise (based on Investigator's assessment) resulting\r\n             from intercurrent pulmonary illnesses including, but not limited to:\r\n\r\n               -  Any underlying pulmonary disorder (eg, pulmonary emboli within three months of\r\n                  the study enrollment or randomization, severe asthma, severe chronic obstructive\r\n                  pulmonary disease, restrictive lung disease, pleural effusion);\r\n\r\n               -  Any autoimmune, connective tissue or inflammatory disorders with pulmonary\r\n                  involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior\r\n                  complete pneumonectomy.\r\n\r\n          -  Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent\r\n             anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1,\r\n             Day 1 (Dose Escalation and First-Line Dose Expansion) or prior to randomization\r\n             (Second-Line Dose Expansion). Participants who require use of bronchodilators, inhaled\r\n             or topical steroids, or local steroid injections may be included in the study.\r\n\r\n          -  Evidence of any leptomeningeal disease.\r\n\r\n          -  Evidence of clinically active spinal cord compression or brain metastases, defined as\r\n             untreated and symptomatic, or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms. Participants with clinically inactive\r\n             or treated brain metastases who are asymptomatic (ie, without neurologic signs or\r\n             symptoms and do not require treatment with corticosteroids or anticonvulsants) may be\r\n             included in the study.\r\n\r\n          -  Inadequate washout period prior to Cycle 1, Day 1 (Dose Escalation and First-Line Dose\r\n             Expansion) or prior to randomization (Second-Line Dose Expansion) defined as:\r\n\r\n               -  Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7\r\n                  days;\r\n\r\n               -  Any systemic anticancer (excluding osimertinib in all Dose Escalation Cohorts and\r\n                  in Second-Line Dose Expansion [Arms 1, 2, and 1b]), including investigational\r\n                  agents, <14 days or 5 half-lives, whichever is longer\r\n\r\n               -  Immune checkpoint inhibitor therapy <5 half-lives\r\n\r\n               -  Major surgery (excluding placement of vascular access) <4 weeks\r\n\r\n               -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field\r\n                  of radiation < 28 days or palliative radiation therapy <14 days\r\n\r\n               -  Chloroquine or hydroxychloroquine 14 days\r\n\r\n               -  Medications or herbal supplemented known to be strong inducers of cytochrome P450\r\n                  (CYP) 3A4 <21 days.\r\n\r\n          -  Has unresolved toxicities from previous anticancer therapy, defined as toxicities\r\n             (other than alopecia) not yet resolved to National Cancer Institute Common Terminology\r\n             Criteria for Adverse Events (NCI-CTCAE) version 5.0, Grade 1 or baseline. Subjects\r\n             with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator\r\n             after consultation with the Sponsor Medical Monitor or designee.\r\n\r\n          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to\r\n             swallow osimertinib, or previous significant bowel resection that would preclude\r\n             adequate absorption of osimertinib.\r\n\r\n          -  Has any primary malignancy other than locally advanced or metastatic NSCLC within 3\r\n             years prior to Cycle 1, Day 1 (Dose Escalation and First-Line Dose Expansion) or\r\n             within 3 years prior to randomization (Second-Line Dose Expansion), except adequately\r\n             resected non-melanoma skin cancer, curatively treated in situ disease, or other solid\r\n             tumors curatively treated.\r\n\r\n          -  Uncontrolled or significant cardiovascular disease prior to Cycle 1, Day 1 (Dose\r\n             Escalation and First-Line Dose Expansion) or prior to randomization (Second-Line Dose\r\n             Expansion) including:\r\n\r\n               -  Mean corrected QT interval using Fridericia's formula (QTcF) prolongation\r\n                  interval of >470 ms for females and >450 ms for males in 3 successive screening\r\n                  measurements\r\n\r\n               -  Left ventricular ejection fraction (LVEF) <50% by either echocardiogram (ECHO) or\r\n                  multigated acquisition (MUGA) scan\r\n\r\n               -  Resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg\r\n\r\n               -  Myocardial infarction within 6 months\r\n\r\n               -  New York Heart Association (NYHA) Classes 2 to 4 congestive heart failure within\r\n                  28 days\r\n\r\n               -  Uncontrolled angina pectoris within 6 months\r\n\r\n               -  Has cardiac arrhythmia requiring antiarrhythmic treatment\r\n\r\n               -  Complete left or right bundle branch block within 6 months\r\n\r\n               -  History of second- or third-degree heart block or PR interval >250 ms within 6\r\n                  months\r\n\r\n               -  History of clinically relevant ventricular arrhythmias, such as ventricular\r\n                  tachycardia, ventricular fibrillation, or Torsade de Pointes\r\n\r\n               -  Has any factors that increase the risk of corrected QT (QTc) prolongation or risk\r\n                  of arrhythmic events, such as heart failure, hypokalemia, congenital long QT\r\n                  syndrome, family history of long QT syndrome, or unexplained sudden death under\r\n                  40 years of age in first-degree relatives, or any concomitant medication known to\r\n                  prolong the QT interval\r\n\r\n          -  Has clinically significant corneal disease\r\n\r\n          -  Any evidence of severe or uncontrolled diseases including active bleeding diatheses,\r\n             active infection, psychiatric illness/social situations, geographical factors,\r\n             substance abuse, or other factors which in the Investigator's opinion makes it\r\n             undesirable for the subject to participate in the study or which would jeopardize\r\n             compliance with the protocol. Screening for chronic conditions is not required.\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer (NSCLC)","interventions":[{"intervention_type":"Drug","name":"Drug: Patritumab deruxtecan","description":"Intravenous infusion at a starting dose of 3.2 mg/kg Q3W"},{"intervention_type":"Drug","name":"Drug: Patritumab deruxtecan","description":"Intravenous infusion at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)"},{"intervention_type":"Drug","name":"Drug: Osimertinib","description":"Oral administration at 40 mg or 80 mg once daily"},{"intervention_type":"Drug","name":"Drug: Osimertinib","description":"Oral administration at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)"},{"intervention_type":"Drug","name":"Drug: Patritumab deruxtecan","description":"Intravenous infusion 5.6 mg/kg Q3W"},{"intervention_type":"Drug","name":"Drug: Patritumab deruxtecan","description":"Intravenous infusion at the selected RCD"},{"intervention_type":"Drug","name":"Drug: Osimertinib","description":"Oral administration at 80 mg once daily"}],"outcomes":[{"outcome_type":"primary","measure":"Dose Escalation: Incidence of Dose-limiting Toxicities (DLT), Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)","time_frame":"From signing of informed consent form up to 40 days (+7 days) after the last dose of study drugs, up to approximately 9 months","description":"A DLT is defined as any TEAE not attributable to disease or disease-related processes that occurs during the DLT evaluation period and is ≥Grade 3, with exceptions as defined in the protocol. A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. AEs will be coded using MedDRA and graded using NCI-CTCAE v5.0."},{"outcome_type":"primary","measure":"Second-line Dose Expansion: Objective Response Rate (ORR)","time_frame":"From start of study treatment until date of documented disease progression or other protocol-defined reason for discontinuation from the study (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 18 months","description":"ORR is defined as the proportion of participants who achieved a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1."},{"outcome_type":"primary","measure":"First-line Dose Expansion: Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)","time_frame":"From signing of informed consent form up to 40 days (+7 days) after the last dose of study drugs, up to approximately 18 months","description":"A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. Adverse events will be coded using MedDRA and will be graded using NCI-CTCAE v5.0."},{"outcome_type":"secondary","measure":"Dose Escalation and First-line Dose Expansion: Objective Response Rate (ORR)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"ORR is defined as the proportion of participants who achieved a best overall response of confirmed CR or confirmed PR as assessed by BICR and Investigator per RECIST v1.1."},{"outcome_type":"secondary","measure":"Second-line Dose Expansion: Objective Response Rate (ORR)","time_frame":"From start of study treatment until the date of documented disease progression or other protocol-defined reason for discontinuation from the study (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 18 months","description":"ORR is defined as the proportion of participants who achieved a best overall response of confirmed CR or PR as assessed by Investigator per RECIST v1.1."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-Line Dose Expansion: Duration of Response (DoR)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. DoR as assessed by BICR and Investigator per RECIST v1.1"},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Disease Control Rate (DCR)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"DCR is defined as the proportion of participants who achieved a best overall response of confirmed CR, confirmed PR, or stable disease (SD) as assessed by BICR and by Investigator per RECIST v1.1."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Time to Response (TTR)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"TTR is defined as the time from the start of study treatment to the date of the first documentation of response (confirmed CR or confirmed PR) in responding participants as assessed by BICR and by Investigator per RECIST v1.1."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Progression-free Survival (PFS)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD as assessed by BICR and by Investigator per RECIST v1.1. or death due to any cause, whichever occurs first"},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Overall Survival (OS)","time_frame":"From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"OS is defined as the time from the start of study treatment to the date of death due to any cause"},{"outcome_type":"secondary","measure":"Second-line Dose Expansion: Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)","time_frame":"From signing of informed consent form up to 40 (+7 days) days after the last dose of study drugs, up to approximately 18 months","description":"A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. Adverse events will be coded using MedDRA and will be graded using NCI-CTCAE v5.0."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA","time_frame":"From the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)","description":"The immunogenicity of patritumab deruxtecan will be assessed."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Maximum Concentration (Cmax)","time_frame":"Patritumab deruxtecan: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)","description":"Cmax will be assessed for patritumab deruxtecan, total anti-HER3 antibody, MAAA-1181a, osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2)."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)","time_frame":"Patritumab deruxtecan: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)","description":"Tmax will be assessed for patritumab deruxtecan, total anti-HER3 antibody, MAAA-1181a, osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2)."},{"outcome_type":"secondary","measure":"Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)","time_frame":"Patritumab deruxtecan: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)","description":"AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for patritumab deruxtecan, total anti-HER3 antibody, MAAA-1181a, osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2)."}]}
{"nct_id":"NCT04869488","start_date":"2021-06-01","phase":"Phase 2","enrollment":250,"brief_title":"A Trial of SHR3162 Combined With Apatinib Mesylate Tablets or SHR3162 Monotherapy in Patients With Metastatic Castration Resistant Prostate Cancer","official_title":"An Open, Multi-center, Phase  Clinical Study of Fluzoparib Combined With Apatinib or Fluzoparib in the Treatment of Metastatic Castration-resistant Prostate Cancer","primary_completion_date":"2023-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-04-30","last_update":"2021-05-03","description":"Cohort 1: Main research purpose: To evaluate the effectiveness of fluzoparib single-drug comparison researcher's choice of chemotherapy for patients with metastatic castration-resistant prostate cancer; Cohort 2, cohort 3: Main research purpose: To evaluate the effectiveness of fluzoparil combined with apatinib mesylate in the treatment of patients with metastatic castration-resistant prostate cancer;","other_id":"SHR3162--202","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Fluzoparib with Apatinib or Fluzoparib monotherapy in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with Abiraterone/Enzalutamine and with or without homologous recombination repair gene mutations.","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Voluntary participation and written informed consent;\r\n\r\n          2. Age 18 years old\r\n\r\n          3. Pathologically diagnosed metastatic castration-resistant prostate adenocarcinoma\r\n\r\n          4. It is confirmed by the central laboratory based on tumor tissue or ctDNA detection\r\n             that it is accompanied by germline or system homologous recombination repair-related\r\n             gene mutations (Cohorts 1 and 3) or not accompanied by homologous recombination\r\n             repair-related gene mutations (Cohort 2)\r\n\r\n          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\r\n\r\n          6. Has a life expectancy of  12 weeks\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Past (within 5 years) or concurrently suffering from other malignant tumors, except\r\n             for cured skin basal cell carcinoma\r\n\r\n          2. Subjects have used PARP inhibitors in the past, including but not limited to olaparib,\r\n             niraparib, and lukapanib; or have used apatinib in the past; or have received\r\n             mitoxantrone and cyclophosphine in the past Treatment with amide or\r\n             platinum-containing chemotherapeutics\r\n\r\n          3. Severe bone injury caused by tumor bone metastasis, pathological fractures or spinal\r\n             cord compression in important parts that occurred within 6 months before being\r\n             informed or is expected to occur in the near future\r\n\r\n          4. The subject has cancerous meningitis, or untreated central nervous system metastasis\r\n\r\n          5. Those who cannot swallow pills normally, or have abnormal gastrointestinal function,\r\n             which may affect drug absorption by the researcher\r\n\r\n          6. Subjects with congenital or acquired immune deficiencies (such as HIV infection), or\r\n             active hepatitis (hepatitis B reference: HBsAg positive and HBV DNA 500 IU/ml;\r\n             hepatitis C reference: HCV antibody positive and HCV virus copy number> upper limit of\r\n             normal )\r\n\r\n          7. According to the judgment of the investigator, the subject has other factors that may\r\n             cause the study to be terminated halfway, such as other serious diseases (including\r\n             mental illness) that require combined treatment, severe laboratory abnormalities,\r\n             family or society, etc. Factors that will affect the safety of subjects or the\r\n             collection of data and samples\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Metastatic Castration Resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Fluzoparib","description":"Fluzoparib Orally twice dailyCohort 1"},{"intervention_type":"Drug","name":"Drug: Enzalutamide OR abiraterone acetate With Prednisone Acetate Tablets","description":"Enzalutamide OR abiraterone acetate Orally once dailyCohort 1"},{"intervention_type":"Drug","name":"Drug: Fluzoparib Combined With Apatinib","description":"Fluzoparib Orally twice daily; Apatinib Orally once dailyCohort 2Cohort 3"}],"outcomes":[{"outcome_type":"primary","measure":"Cohort 1: Radiological progression-free survival (rPFS) evaluated by BIRC based on the RECIST v1.1 standard and the PCWG3 standard","time_frame":"up to 2 years","description":"The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression."},{"outcome_type":"primary","measure":"Cohort 2, Cohort 3: Comprehensive response rate","time_frame":"up to 2 years"},{"outcome_type":"secondary","measure":"Radiological progression-free survival (rPFS)","time_frame":"up to 2 years","description":"The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression."},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"At the time point of every 8 weeks，up to 2 years"},{"outcome_type":"secondary","measure":"PSA response rate","time_frame":"At the time point of every 4 weeks，up to 2 years"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"At the time point of every 2 months，up to 2 year","description":"Number of Participants with Overall Survival (OS)"}]}
{"nct_id":"NCT04856774","start_date":"2021-06-01","phase":"Phase 1/Phase 2","enrollment":113,"brief_title":"Trial of SHR-1701 Plus BP102 in Subjects With Selected Solid Tumors","official_title":"A Multicenter, Open-Label, Phase Ib/II Trial of SHR-1701 Plus BP102 in Subjects With Selected Solid Tumors","primary_completion_date":"2021-12-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-30","last_update":"2021-08-16","description":"The main purpose of this study was to assess the safety, tolerability, and efficacy when combining SHR-1701 and BP102 in participants with certain cancers. This study was conducted in 2 phases, Phase Ib and Phase II.","other_id":"SHR-1701-II-207","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Histologically or cytologically confirmed solid malignancy that is metastatic or\r\n             unresectable for which standard curative or palliative measures do not exist or are no\r\n             longer effective (phase Ib)\r\n\r\n          2. Histologically or cytologically confirmed metastatic or locally advanced solid tumors\r\n             of the selected indications. (Phase II).\r\n\r\n          3. .Life expectancy exceeds 12 weeeks;\r\n\r\n          4. The Eastern Cancer Cooperative Group (ECOG) has a performance score of 0 or 1;\r\n\r\n          5. Normal organ and marrow function;\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has known active central nervous system (CNS) metastases. Subjects with previously\r\n             treated brain metastases may participate provided they are stable.\r\n\r\n          2. A history of human immunodeficiency virus (HIV) infection is known, or has an active\r\n             autoimmune disease.\r\n\r\n          3. History of interstitial lung disease or pneumonia requiring oral or intravenous\r\n             steroids.\r\n\r\n          4. Has moderate or severe cardiovascular disease;\r\n\r\n          5. Active HBV(hepatitis B) or HCV (Hepatitis C virus)-infected subjects;\r\n\r\n          6. Any other malignancies within 5 years except for those with negligible risk of\r\n             metastasis or death.\r\n      ","sponsor":"Suzhou Suncadia Biopharmaceuticals Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: SHR-1701BP102","description":"Drug: SHR-1701 IV infusion\r\nDrug: BP102 IV infusion\r\nPhase Ib: SHR-1701 30mg/kg + BP102 15mg/kg Q3w as starting dose, until recommended phase 2 dose is determined."}],"outcomes":[{"outcome_type":"primary","measure":"recommended phase 2 dose (Phase Ib)","time_frame":"At the end of Cycle 2 (each cycle is 21 days)"},{"outcome_type":"primary","measure":"Objective response rate (ORR)","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Dose Limiting Toxicity (DLT) (Phase 1b)","time_frame":"At the end of Cycle 2 (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Number of participants with treatment emergent adverse events (TEAEs)","time_frame":"For each participant, from the first dose till 90 days after the last dose"},{"outcome_type":"secondary","measure":"Number of participants with treatment emergent serious adverse events (SAEs)","time_frame":"For each participant, from the first dose till 90 days after the last dose"},{"outcome_type":"secondary","measure":"ORR","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Time to response(TTR)","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"2 years"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"2 years"}]}
{"nct_id":"NCT04822961","start_date":"2021-06-01","phase":"Phase 2","enrollment":165,"brief_title":"Senaparib in mCRPC Patients With Homologous Recombination Repair Gene Alterations After Docetaxel Treatment","official_title":"A Randomized, Double-Blinded, Placebo-Controlled, Multicenter, Phase II Study to Evaluate Senaparib in mCRPC Patients With Homologous Recombination Repair Gene Alterations After Docetaxel Treatment","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-05-31","last_update":"2021-03-30","description":"The purpose of this study is to evaluate the efficacy and safety of Senaparib in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations after docetaxel treatment","other_id":"IMP4297-202","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","intervention_model_description":"Randomized, Double-Blinded, Placebo-Controlled","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Patients must voluntarily participate in this clinical study. Be willing written\r\n             informed consent form (ICF) prior to any study activity.\r\n\r\n          2. Male 18 years of age on the day of signing the ICF.\r\n\r\n          3. Patients must have histologically or cytologically confirmed prostate adenocarcinoma.\r\n\r\n          4. Surgically or medically castrated, with serum testosterone levels of 50 ng/dL (1.73\r\n             nmol/L). If the patient is being treated with LHRH agonists/antagonists (patient who\r\n             have not undergone orchiectomy), this therapy must be continued throughout the study.\r\n\r\n          5. Patients have adequate organ functions, as indicated by the following laboratory\r\n             values (had not received blood transfusion, apheresis infusion, erythropoietin,\r\n             granulocyte colony-stimulating factor (G-CSF), and other relevant medical support\r\n             within 14 days before the administration of study drug).\r\n\r\n          6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to\r\n             2.\r\n\r\n          7. Male patients must use a condom during treatment and for 3 months after the last dose\r\n             of study drug when having sexual intercourse with a woman of childbearing potential.\r\n             Female partners of male patients should also use an acceptable method of contraception\r\n             if they are of childbearing potential.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Previous allogenic bone marrow transplant or double umbilical cord blood\r\n             transplantation (dUCBT).\r\n\r\n          2. Prior treatment with a polyadenosine 5'diphosphoribose polymerisation (PARP)\r\n             inhibitor, including Senaparib.\r\n\r\n          3. Patients with a known hypersensitivity to Senaparib or any of the component of\r\n             Senaparib.\r\n\r\n          4. Initiating bisphosphonate/denosumab therapy or adjusting bisphosphonate/denosumab\r\n             dose/regimen within 28 days prior to the first dose of study drug. Patients on a\r\n             stable bisphosphonate/denosumab regimen are eligible and may continue.\r\n\r\n          5. Patients who have received strong inhibitors/inducers of CYP3A4 which cannot be\r\n             discontinued 21 days prior to the first dose of study drug and withheld throughout the\r\n             study drug treatment. Patients received phenobarbital/enzalutamide will require a\r\n             5-week washout prior to the first dose of study drug.\r\n\r\n          6. Patients with MDS or AML, or with clinical features suggestive of MDS or AML.\r\n\r\n          7. Patients with serious acute or chronic infections.\r\n\r\n          8. Patients who have received a live virus or bacterial or RNA vaccination within 28 days\r\n             prior to the first dose of study drug.\r\n\r\n          9. Patients are unable or unwilling to abide by the study protocol or cooperate fully\r\n             with the investigator or designee.\r\n      ","sponsor":"Impact Therapeutics, Inc.","sponsor_type":"Industry","conditions":"mCRPC","interventions":[{"intervention_type":"Drug","name":"Drug: Placebo","description":"Senaparib-matched placebo capsules"},{"intervention_type":"Drug","name":"Drug: Senaparib","description":"20 mg capsules"}],"outcomes":[{"outcome_type":"secondary","measure":"Objective response rate (ORR) according to RECIST v1.1 assessed by BICR","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on radiographic response rate, compared with the placebo, in mCRPC patients with HRR gene alterations who have measurable lesion assessed by BICR Unit of measure: ORR by RECISTv1.1"},{"outcome_type":"primary","measure":"rPFS assessed by BICR","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on radiographic progression free survival (rPFS), compared with the placebo, in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations assessed by Blinded Independent Central Review (BICR) Unit of measure: rPFS"},{"outcome_type":"secondary","measure":"rPFS assessed by the investigator","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on rPFS, compared with the placebo, in mCRPC patients with HRR gene alterations assessed by the investigator Unit of measure: rPFS"},{"outcome_type":"secondary","measure":"rPFS in BRCA1, BRCA2 or ATM mutation positive patients assessed by BICR. Mutation positive indicates deleterious or suspected deleterious mutation.","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on rPFS, compared with the placebo, in mCRPC patients with breast cancer susceptibility gene (BRCA) 1, BRCA2 or Ataxia telangiectasia mutated (ATM) mutation positive assessed by BICR Unit of measure: rPFS"},{"outcome_type":"secondary","measure":"Time to PSA progression","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on time to prostate-specific antigen (PSA) progression, compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: Time in days"},{"outcome_type":"secondary","measure":"Time to pain progression","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on time to pain progression, compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: Time in days. BPI-SF with a numeric rating scale will be used along analgesic use log to evaluate the pain progression. The method of categorizing analgesics and adjuvant medications for the treatment of cancer pain will be based on the AQA score which is a modified version of the World Health Organization-Analgesic Treatment Ladder (WHOAL). The scoring will be based on the type of analgesic used and the daily dose required, which will be translated into a AQA score (1-7) calculated every cycle."},{"outcome_type":"secondary","measure":"Time from randomization to the first SSRE","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on time to the first symptomatic skeletal related events (SSRE), compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: Time in days"},{"outcome_type":"secondary","measure":"ORR according to RECIST v1.1 assessed by the investigator","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on radiographic response rate, compared with the placebo, in mCRPC patients with HRR gene alterations who have measurable lesion assessed by the investigator Unit of measure: ORR by RECISTv1.1"},{"outcome_type":"secondary","measure":"PSA response rate according to PCWG3 criteria assessed by local laboratory","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on PSA response rate, compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: PCWG3 based on PSA value in ng/mL"},{"outcome_type":"secondary","measure":"PFS2","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on second progression (PFS2), compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: PFS2"},{"outcome_type":"secondary","measure":"OS","time_frame":"80 weeks","description":"To evaluate the impact of Senaparib on overall survival (OS), compared with the placebo, in mCRPC patients with HRR gene alterations Unit of measure: OS"},{"outcome_type":"secondary","measure":"Safety endpoints","time_frame":"80 weeks","description":"Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0."},{"outcome_type":"secondary","measure":"plasma PK profile","time_frame":"80 weeks","description":"To characterize the plasma PK profile of Senaparib via population PK (popPK) modeling"}]}
{"nct_id":"NCT04814108","start_date":"2021-06-01","phase":"Phase 2","enrollment":110,"brief_title":"A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma","official_title":"A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women With Recurrent or Persistent Uterine Serous Carcinoma","primary_completion_date":"2022-12-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-01","last_update":"2021-08-24","description":"This is a Phase 2 study to evaluate the clinical activity, safety, pharmacokinetics (PK), and related biomarkers of ZN-c3 in adult women with recurrent or persistent uterine serous carcinoma (USC).","other_id":"ZN-c3-004","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Females age 18 years of age at the time of informed consent.\r\n\r\n          -  Recurrent or persistent USC.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.\r\n\r\n          -  Measurable disease, defined as at least one lesion that can be accurately measured per\r\n             revised Response Evaluation Criteria in Solid Tumors RECIST Guideline version 1.1\r\n             criteria.\r\n\r\n          -  Adequate hematologic and organ function.\r\n\r\n          -  Females of childbearing potential must agree to use an effective method of\r\n             contraception per institutional standard prior to the first dose and for 90 days after\r\n             the last dose of ZN c3.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior treatment with a cell cycle checkpoint inhibitor.\r\n\r\n          -  Prior therapy with ZN-c3 or any other WEE1 inhibitor.\r\n\r\n          -  A serious illness or medical condition(s).\r\n\r\n          -  Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2\r\n             neuropathy, alopecia, or skin pigmentation).\r\n\r\n          -  Pregnant or lactating females (including the cessation of lactation) or females of\r\n             childbearing potential who have a positive serum pregnancy test within 28 days prior\r\n             to C1D1.\r\n\r\n          -  Subjects with active (uncontrolled, metastatic) second malignancies or requiring\r\n             therapy.\r\n\r\n          -  12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of\r\n             > 480 ms at screening, except for subjects with atrioventricular pacemakers or other\r\n             conditions (e.g., right bundle branch block) that render the QT measurement invalid.\r\n\r\n          -  History or current evidence of congenital or family history of long QT syndrome.\r\n      ","sponsor":"K-Group Beta","sponsor_type":"Industry","conditions":"Uterine Serous Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: ZN-c3","description":"ZN-c3 is an investigational drug."}],"outcomes":[{"outcome_type":"primary","measure":"To investigate the antitumor activity of ZN-c3 based on the objective response rate (ORR).","time_frame":"2 years","description":"Objective response rate (ORR) as defined by the revised Response Evaluation Criteria in Solid Tumors RECIST Guideline version 1.1"},{"outcome_type":"secondary","measure":"To investigate the antitumor clinical activity based on Duration of Response (DOR)","time_frame":"2 years","description":"Duration of Response (DOR) as defined by the revised RECIST Guideline version 1.1"},{"outcome_type":"secondary","measure":"To investigate the antitumor clinical activity based on Progression-Free Survival (PFS)","time_frame":"2 years","description":"Progression- free survival (PFS) as defined by the revised RECIST Guideline version 1.1"},{"outcome_type":"secondary","measure":"To investigate the safety and tolerability of ZN-c3","time_frame":"2 years","description":"Frequency and severity of AEs, including laboratory abnormalities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0."}]}
{"nct_id":"NCT04884360","start_date":"2021-05-31","phase":"Phase 3","enrollment":420,"brief_title":"D9319C00001- 1L OC Mono Global RCT","official_title":"A Randomised, Double-blind, Placebo-controlled, Phase III Study of Olaparib Maintenance Monotherapy in Participants With BRCA Wild Type Advanced High Grade Serous or Endometrioid Ovarian Cancer Following Response to Standard First-line Platinum-based Chemotherapy (MONO-OLA1)","primary_completion_date":"2024-07-02","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-07-02","last_update":"2021-09-14","description":"This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of maintenance olaparib compared with placebo in BRCAwt participants with Stage III to IV high grade serous or endometroid ovarian cancer (including fallopian tube cancer or primary peritoneal cancer) who are in complete or partial response following treatment with standard first-line platinum-based chemotherapy.","other_id":"D9319C00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  1,Participants must be 18 years at the time of (pre-)screening\r\n\r\n             2,Histological and staging criteria:Female participants who must have histologically\r\n             newly diagnosed high-grade serous or endometrioid ovarian cancer, fallopian tube\r\n             cancer, or primary peritoneal cancer that is Stage III or IV according to the\r\n             International FIGO 2009.\r\n\r\n             3, Participants are eligible if they fulfil any of the following surgical criteria:\r\n\r\n          -  Stage III: primary debulking surgery with macroscopic residual disease post-surgery,\r\n             neoadjuvant chemotherapy, or inoperable.\r\n\r\n          -  Stage IV: primary debulking surgery regardless of residual disease, neoadjuvant\r\n             chemotherapy, or inoperable.\r\n\r\n             4, Chemotherapy criteria:\r\n\r\n          -  Participants must have received platinum-based chemotherapy consisting of a minimum of\r\n             6 treatment cycles and a maximum of 9, however, if platinum-based therapy must be\r\n             discontinued early as a result of toxicities specifically related to the platinum\r\n             regimen, participants must have received a minimum of 4 cycles of the platinum\r\n             regimen.\r\n\r\n          -  Participants must have, in the opinion of the investigator, clinical CR or PR as per\r\n             RECIST 1.1 criteria with no measurable lesion > 2 cm on the post-treatment scan and\r\n             have no clinical evidence of disease progression or a rising CA-125 level (see\r\n             inclusion criterion 5), following completion of this chemotherapy course.\r\n\r\n          -  A participant who received interval debulking surgery must have had  2 postoperative\r\n             cycles of platinum-based therapy.\r\n\r\n             5, Participants must meet one of the criteria specified below for pre-treatment CA-125\r\n             measurements as follows:\r\n\r\n          -  CA-125 in the normal range or\r\n\r\n          -  CA-125 decrease by  90% during their front-line therapy that is stable for at least 7\r\n             days (ie, no increase > 15% from nadir. If the first value is greater than the upper\r\n             limit of normal (ULN), a second assessment must be performed at least 7 days after the\r\n             first. If the second assessment is > 15% more than the first value, the participant is\r\n             not eligible).\r\n\r\n             6, Participants should not have received bevacizumab with first-line chemotherapy or\r\n             be planned to receive bevacizumab maintenance therapy.\r\n\r\n             7, ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks\r\n             prior to randomisation.\r\n\r\n             8, Provision, at pre-screening, of a formalin-fixed, paraffin-embedded (FFPE) tumour\r\n             sample to assess tBRCA status and for HRD testing centrally. The centrally performed\r\n             tBRCA test results must be available prior to randomisation and must indicate that the\r\n             participant has a BRCAwt tumour, defined by the absence of a deleterious or suspected\r\n             deleterious BRCA mutation by central testing.\r\n\r\n             9, Adequate organ and marrow function.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  1, Participants with stable disease or progressive disease on the post-treatment scan\r\n             or clinical evidence of progression at the end of the participant's first-line\r\n             chemotherapy treatment, or any evidence of progressive disease prior to randomization.\r\n\r\n             2, Participant has mucinous or clear cell subtypes of epithelial ovarian cancer,\r\n             carcinosarcoma, undifferentiated ovarian cancer, non-epithelial ovarian cancer,\r\n             borderline tumours or low grade epithelial ovarian tumours (applies to fallopian tube\r\n             and primary peritoneal tumours where applicable).\r\n\r\n             3, Participants with Stage III disease who have had complete cytoreduction (ie, no\r\n             macroscopic residual disease) at their primary debulking surgery.\r\n\r\n             4, Participants who have undergone  2 debulking (cytoreductive) surgeries.\r\n\r\n             5, History of another primary malignancy except for malignancy treated with curative\r\n             intent with no known active disease  5 years before the first dose of study\r\n             intervention including adequately treated non-melanoma skin cancer, curatively treated\r\n             in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, Grade 1\r\n             endometrial carcinoma. Participants with a history of localised triple negative breast\r\n             cancer may be eligible, provided they completed their adjuvant chemotherapy more than\r\n             three years prior to registration, and that the participant remains free of recurrent\r\n             or metastatic disease.\r\n\r\n             6, Persistent toxicities (CTCAE Grade 2) caused by previous anticancer therapy,\r\n             excluding alopecia and CTCAE Grade 2 peripheral neuropathy. Participants with\r\n             irreversible toxicity that is not reasonably expected to be exacerbated by study\r\n             intervention may be included after consultation with the AstraZeneca study physician.\r\n\r\n             7, Participant is immunocompromised\r\n\r\n             8, Prior exposure to a PARP inhibitor, including olaparib\r\n\r\n             9, Any concurrent anticancer treatment\r\n\r\n             10, Currently pregnant or breast-feeding\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Olaparib","description":"Olaparib tablets 300 mg oral twice daily"},{"intervention_type":"Other","name":"Other: Matching placebo","description":"Matching placebo tablets taken orally at a dose of 300 mg twice daily"}],"outcomes":[{"outcome_type":"primary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III/IV ovarian cancer with a BRCAwt HRD positive tumour and a CR/PR following standard 1st line platinum based chemotherapy treatment.","time_frame":"Approximately 3 years","description":"PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause."},{"outcome_type":"primary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III/IV ovarian cancer with a BRCAwt tumour and a CR/PR following standard 1st line platinum-based chemotherapy treatment.","time_frame":"Approximately 3 years","description":"PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of OS in participants with Stage III/IV ovarian cancer with a BRCAwt HRD positive tumour and a CR/PR following standard first line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"OS is defined as time from randomisation until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of OS in participants with Stage III/IV ovarian cancer with a BRCAwt tumour and a CR/PR following standard first-line platinum-based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"OS is defined as time from randomisation until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of TFST in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum-based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"TFST is defined as time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of TFST in participants with a BRCAwt tumour and a CR or PR following standard first line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"TFST is defined as time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS2 in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS2 in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of TSST in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"TSST is defined as time from randomisation until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of TSST in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 4 years","description":"TSST is defined as time from randomisation until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to TDT in participants with a BRCAwt HRD positive tumour and a CR/PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 3 years","description":"TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death."},{"outcome_type":"secondary","measure":"To demonstrate superiority of olaparib as maintenance treatment relative to placebo by assessment of time to TDT in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.","time_frame":"Approximately 3 years","description":"TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to earliest progression by RECIST 1.1/CA 125/death in participants with a BRCAwt HRD positive tumour and a CR/PR following 1st line platinum based chemotherapy","time_frame":"Approximately 3 years","description":"Time to earliest progression by RECIST 1.1/CA 125 or death will be measured from time of randomisation to the earlier date of RECIST 1.1/CA-125 progression or death by any cause."},{"outcome_type":"secondary","measure":"Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to earliest progression by RECIST 1.1/CA 125/death in participants with a BRCAwt tumour and a CR/PR following first-line platinum based chemotherapy.","time_frame":"Approximately 3 years","description":"Time to earliest progression by RECIST 1.1 or CA 125 or death will be measured from time of randomisation to the earlier date of RECIST 1.1 or CA-125 progression or death by any cause."},{"outcome_type":"secondary","measure":"Assess Health-related quality of life in participants treated with olaparib compared with placebo in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment","time_frame":"Approximately 3 years","description":"Change from baseline in EORTC QLQ C30."},{"outcome_type":"secondary","measure":"Assess Health-related quality of life in participants treated with olaparib compared with placebo in participants with BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment","time_frame":"Approximately 3 years","description":"Change from baseline in EORTC QLQ C30."},{"outcome_type":"other","measure":"Assess the safety and tolerability of olaparib in terms of AEs/SAEs as compared with placebo in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum-based chemotherapy treatment.","time_frame":"Approximately 3 years","description":"Graded according to the National Cancer Institute (NCI CTCAE)"}]}
{"nct_id":"NCT04884009","start_date":"2021-05-31","phase":"Phase 2","enrollment":106,"brief_title":"A Trial of SHR-1701 in Combination With and Without Famitinib Malate in Patients With Extensive Stage Small Cell Lung Cancer","official_title":"An Open-label, Multicenter Phase Study of SHR-1701 in Combination With or Without Famitinib Malate for the Treatment of Extensive Stage Small Cell Lung Cancer After Previous Systemic Chemotherapy Failure","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2022-12-31","last_update":"2021-05-12","description":"The study is being conducted to evaluate the efficacy and safety of SHR-1701 in combination with or without famitinib malate for the treatment of extensive stage small cell lung cancer after the failure of previous systemic chemotherapy","other_id":"SHR-1701-II-209","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"SHR-1701 in combination with or without famitinib","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Patients voluntarily participated in the clinical study, understood the study\r\n             procedures and are able to sign the informed consent form.\r\n\r\n          2. 18 to 75 years old, male or female.\r\n\r\n          3. Histologically or cytologically confirmed extensive stage small cell lung\r\n             cancerED-SCLC.\r\n\r\n          4. ECOG Performance Status of 0 or 1.\r\n\r\n          5. Adequate hematological, hepatic and renal function.\r\n\r\n          6. Female subjects of child-bearing potential must have a negative serum HCG test before\r\n             treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Histologically or cytologically confirmed mixed SCLC and NSCLC.\r\n\r\n          2. Untreated central nervous system metastases.\r\n\r\n          3. Cancerous meningitis (meningeal metastasis).\r\n\r\n          4. Uncontrolled pleural effusion, pericardial effusion or ascites.\r\n\r\n          5. Tumor infiltration into the great vessels on imaging;\r\n\r\n          6. Hemoptysis symptoms and maximum daily hemoptysis  2.5ml occurred within 1 month.\r\n\r\n          7. Uncontrolled tumor-related pain.\r\n\r\n          8. Malignancies other than SCLC within 5 years.\r\n\r\n          9. Systemic antitumor therapy was received 4 weeks prior to trial treatment.\r\n\r\n         10. History of autoimmune diseases.\r\n\r\n         11. Significant cardiovascular disease.\r\n\r\n         12. Inadequately controlled hypertension.\r\n\r\n         13. Known history of testing positive test for HIV or known AIDS.\r\n\r\n         14. Patients with active hepatitis B or hepatitis C\r\n\r\n         15. Severe infections within 4 weeks prior to trial treatment.\r\n\r\n         16. Active tuberculosis.\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SHR-1701 Famitinib","description":"SHR-1701+ Famitinib"},{"intervention_type":"Drug","name":"Drug: SHR-1701","description":"SHR-1701"}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate (ORR) based on RECIST 1.1 criteria","time_frame":"up to approximately 1 year."},{"outcome_type":"secondary","measure":"Progression free survival (PFS) based on RECIST 1.1 criteria","time_frame":"up to approximately 1 year."},{"outcome_type":"secondary","measure":"Disease control rate (DCR) based on RECIST 1.1 criteria","time_frame":"up to approximately 1 year."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"up to approximately 1 year"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"up to approximately 1 year"},{"outcome_type":"secondary","measure":"AEs+ SAEs determined by NCI-CTCAE V5.0","time_frame":"Baseline until up to 90 days after end of treatment."}]}
{"nct_id":"NCT04815291","start_date":"2021-05-31","phase":"N/A","enrollment":500,"brief_title":"Streamlined Localization Using SCOUT at Biopsy (STREAMLoc )","official_title":"STREAMLoc- Streamlined Localization Using SCOUT at Biopsy: An Analysis of Process Improvement, Cost Savings and Enhanced Patient Experience.","primary_completion_date":"2022-11-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2022-11-30","last_update":"2021-03-25","description":"This registry is intended to demonstrate the utility of the SCOUT Surgical Guidance system to improve workflow and efficiency in Canadian centers diagnosing and treating breast cancer. The secondary objective is to further evaluate the safety and performance of the SCOUT Surgical Guidance system in 500 consented BI-RADS 4C/5 according to the IFU.","other_id":"SCOUT2021","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":80,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Woman >18 years and < 80 years of age;\r\n\r\n          2. Classified as Breast Imaging Reporting and Data System (BI-RADS) 4C or 5;\r\n\r\n          3. Lesion depth is < 6 cm from skin surface;\r\n\r\n          4. Non-palpable lesions;\r\n\r\n          5. Informed consent obtained.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Multicentric breast cancer;\r\n\r\n          2. Pregnant or lactating;\r\n\r\n          3. Known or suspected nickel-titanium allergy.\r\n      ","sponsor":"Merit Medical Systems, Inc.","sponsor_type":"Industry","conditions":"Breast Cancer","interventions":[{"intervention_type":"Device","name":"Device: Receives SCOUT at biopsy","description":"SCOUT Reflector"}],"outcomes":[{"outcome_type":"primary","measure":"Number of invasive visits","time_frame":"up to 1 year","description":"Number of visits to the breast centre for an invasive procedure between biopsy and surgery"}]}
{"nct_id":"NCT04808531","start_date":"2021-05-31","phase":"Phase 3","enrollment":360,"brief_title":"NanaBis an Oro-buccal Administered delta9-Tetrahydrocannabinol (d9-THC) & Cannabidiol (CBD) Medicine for the Management of Bone Pain From Metastatic Cancers","official_title":"NanaBis an Oro-buccal Administered Equimolar d9-THC & CBD Formulation as Monotherapy for Management of Opioid Requiring Bone Pain Due to Metastatic Cancer: Phase 3 Multi Centre Blinded Randomized Withdrawal Active & Placebo Controlled Trial","primary_completion_date":"2023-08-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-01-31","last_update":"2021-03-22","description":"This is a multi-centre, long term, double blind, clinical protocol for NanaBis as a monotherapy treatment in participants 18-70 years of age with cancer related pain.","other_id":"MDC-NB-P3-01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":70,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        At Screening Phase\r\n\r\n        Participants must fulfil all of the following criteria:\r\n\r\n          -  Prospective male and female participants in the age range 18-70 years\r\n\r\n          -  Metastatic bone pain from a cancer diagnosis is the only major cause of pain. Markers\r\n             of disease progression (e.g. tenderness or unrelieved pain with changes in posture)\r\n             may need to be randomised\r\n\r\n          -  Pathology (blood, imaging) confirmed metastatic bone cancer\r\n\r\n          -  Meet International Classification of Diseases-10 (ICD-10) codes for pain management\r\n             criteria (i.e., bone cancer pain)\r\n\r\n          -  During the screening period, the participant is on stable opioid pain management and\r\n             pain severity (NPRS)  8 with a maximum variation of  1\r\n\r\n          -  Pain Detect score > 18\r\n\r\n          -  Participant willing and able to provide informed consent and follow study procedures\r\n\r\n               1. including agreeing to not drive or operate heavy machinery; and\r\n\r\n               2. females of child-bearing potential agree to use reliable contraception during the\r\n                  duration of the clinical trial\r\n\r\n        Exclusion Criteria:\r\n\r\n        At Screening Phase\r\n\r\n        Participants will be excluded if they meet any of the following criteria that include:\r\n\r\n          -  History of epilepsy or recurrent seizures\r\n\r\n          -  Moderate to severe medical conditions such as\r\n\r\n               1. severe hepatic;\r\n\r\n               2. cardiovascular or renal impairment; or\r\n\r\n               3. psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced\r\n                  psychosis, severe mood disorders), that would be assessed at the medical screen\r\n\r\n          -  Presence of substance abuse disorder such as nicotine or alcohol, or other illicit or\r\n             prescription drug dependence (e.g., opioid dependence), or methadone or buprenorphine\r\n             treatment for opioid dependence\r\n\r\n          -  Women who are pregnant, lactating or planning to become pregnant\r\n\r\n          -  Identified concerns by the nursing / medical team relevant to the safe storage of\r\n             medications (i.e., NanaBis or standard medical therapy)\r\n\r\n          -  Participant may not be available for follow up (i.e., planned or expected travel or\r\n             other)\r\n      ","sponsor":"Medlab Clinical","sponsor_type":"Industry","conditions":"Cancer Related Pain","interventions":[{"intervention_type":"Drug","name":"Drug: NanaBis","description":"NanaBis is a nanoparticle water soluble equimolar solution of d9-THC & CBD. One dose is equivalent to 2 actuations of the pump delivering 280 L volume containing 2.5 mg d9-THC and 2.5 mg CBD"},{"intervention_type":"Drug","name":"Drug: Oxycodone CR","description":"Oxycodone CR tablet is an opioid agonist supplied in 10 mg, 15 mg, 20 mg, 30 mg,40 mg, 60 mg and 80 mg tablets for oral administration. The tablet strengths describe the amount of oxycodone per tablet as the hydrochloride salt."},{"intervention_type":"Drug","name":"Drug: Placebo Spray","description":"Placebo comparator used against both NanaBis and Oxycodone depending on randomisation of arms."},{"intervention_type":"Drug","name":"Drug: Placebo Tablet","description":"Placebo comparator used against both NanaBis and Oxycodone depending on randomisation of arms."}],"outcomes":[{"outcome_type":"primary","measure":"Significant changes in responders with NanaBis™ spray over placebo (p<0.05)","time_frame":"6 weeks","description":"To demonstrate that at the end of the 6-week study period the proportion of responders in the NanaBis™ group shows significant change than the proportion of responders in the placebo group"},{"outcome_type":"primary","measure":"Comparable efficacy in proportion of responders from NanaBis™ spray to the proportion of responders to Oxycodone CR","time_frame":"6 weeks","description":"To demonstrate that at the end of the 6-week study period the proportion of responders in the NanaBis™ group is similar to the proportion of responders in the Oxycodone group"},{"outcome_type":"secondary","measure":"Significant change in the Health-Related Quality of Life Scores Form (36) Health Survey (SF-36) with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR","time_frame":"6 weeks","description":"To demonstrate that at the end of the 6-week study period the Health-Related Quality of Life scores in the Scores Form (36) Health Survey (SF-36) for the NanaBis™ group are significantly changed than in the Placebo group and is similar to the Oxycodone group.\r\nChange in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period [Time Frame: Baseline; End of Week 3 (3 weeks)]; and at End of Treatment Period [Time Frame: Baseline; End of Week 6 (3 weeks)]; and at End of Compassionate Period [Time Frame: Baseline; End of Week 18 (12 weeks)]\r\nThe Scores Form 36 (SF-36) includes 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant scores. Higher scores indicate improvement in health. Domain scale scores 0 (negative health) to 100 (positive health). 100 represents the best health state."},{"outcome_type":"secondary","measure":"Significant change in the painDETECT score with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR","time_frame":"18 weeks","description":"painDETECT Assessment at Baseline [Time Frame: Baseline]. painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component.\r\npainDETECT Assessment for Participants at End of Titration and Optimal Dose Period [Time Frame: End of Week 1 to 3]; painDETECT Assessment for Participants at End of the Treatment Period [Time Frame: End of Weeks 4 to 6]; painDETECT Assessment for Participants at End of the Compassionate Period [Time Frame: End of Weeks 7 to 18].\r\npainDETECT is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being \"negative\" (no neuropathic pain component). Value between 19 and 38 as being \"positive\" (presence of neuropathic component)\". Values from 13 to 18 are scored as being \"unclear\"."},{"outcome_type":"secondary","measure":"NanaBis™ Adverse Events","time_frame":"18 weeks","description":"To demonstrate that at the end of the 6-week study period that NanaBis™ is safe and tolerable. The daily use of NanaBis™ oro-buccal spray reduces the severity of Treatment-Emergent Adverse Events (safety and tolerability). [Time Frame: Change from Baseline and Titration and Treatment in UKU-Side Effects Rating Scale for Patients (UKU-SERS-Pat) at Weeks 1 to 3 and 4 to 6.]\r\nDoes the daily use of NanaBis™ oro-buccal spray reduce the severity of Treatment-Emergent Adverse Events (safety and tolerability). [Time Frame: Change during Compassionate Use in UKU-SERS-Pat at Weeks 7 to 18.]\r\nChanges in validated UKU-SERS-Pat scale range is 0 to 3 for rating the degree of severity (mild, moderate or severe) and a second scale for the investigator that assigns a casual relationship of improbable, possible or probable."},{"outcome_type":"secondary","measure":"Fifty percent or greater request compassionate extension with NanaBis™ spray","time_frame":"12 weeks","description":"To demonstrate that at the end of the 6-week study period that after unblinding, half or more of the NanaBis™ group prefer further treatment with NanaBis™ in the compassionate extension phase"}]}
{"nct_id":"NCT04807972","start_date":"2021-05-28","phase":"Phase 2","enrollment":129,"brief_title":"Study to Evaluate Adverse Events and Change in Disease Activity When Intravenous (IV) Infusion of ABBV-927 is Administered in Combination With IV Modified FOLFIRINOX (mFFX) With or Without IV Budigalimab Compared to mFFX in Adult Participants With Untreated Pancreatic Cancer Metastasis","official_title":"A Phase 1b/2, Randomized, Controlled, Open-Label Study Evaluating the Safety and Efficacy of ABBV-927 Administered in Combination With Modified FOLFIRINOX (mFFX) With or Without Budigalimab Compared to mFFX in Subjects With Untreated Metastatic Pancreatic Adenocarcinoma","primary_completion_date":"2024-08-03","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-06-06","last_update":"2021-06-29","description":"Metastatic Pancreatic Cancer Disease is one of the most aggressive and deadliest forms of cancer with very poor survival. This study will evaluate adverse events and change in disease activity in participants 18 to 75 years of age with a body weight greater than or equal to 35 kg with Metastatic Pancreatic Cancer Disease treated with Intravenous (IV) infusion of modified FOLFIRINOX (mFFX) combined with IV infusions of ABBV-927 with or without Budigalimab. ABBV-927 and Budigalimab are the investigational drugs being developed for treatment of Metastatic Pancreatic Cancer Disease. In this study, doctors will enroll participants between 18 and 75 years of age with a body weight greater than or equal to 35 kg diagnosed diagnosed with Metastatic Pancreatic Cancer Disease in 4 different groups, called treatment arms. Each group will receive different treatments. Approximately 129 adult participants will be enrolled in the study across approximately 27 sites worldwide. Participants will receive ABBV-927 and Budigalimab as Intravenous (IV) Infusion in Phase 1b and Phase 2 on day 3 of every 28 day cycle, modified FOLFIRINOX as IV Infusion in Phase 1b and Phase 2 on Day1 and Day 15 of every 28 day cycle up to maximum of 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.","other_id":"M20-732","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Body weight >= 35 kg.\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with\r\n             metastatic disease.\r\n\r\n          -  Measurable disease per Response Evaluation Criteria for Solid Tumors Version 1.1\r\n             (RECIST v1.1).\r\n\r\n          -  Prior history of or clinically stable concurrent malignancy are eligible for\r\n             enrollment provided the malignancy is clinically insignificant, no treatment is\r\n             required, and the participant is clinically stable.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participants with locally advanced disease.\r\n\r\n          -  Participants with neuroendocrine (carcinoid, islet cell) or acinar pancreatic\r\n             carcinoma.\r\n\r\n          -  Prior radiotherapy, surgery, or systemic anti-cancer therapy for the treatment of\r\n             metastatic pancreatic adenocarcinoma.\r\n\r\n          -  Prior radiotherapy, surgery, or systemic anti-cancer therapy in the adjuvant setting,\r\n             or earlier, within the last 4 months.\r\n\r\n          -  Prior radiotherapy to any measurable metastatic lesion at any time.\r\n\r\n          -  Clinically significant third-space fluid accumulation (e.g., ascites or pleural\r\n             effusion).\r\n\r\n          -  Known metastases to the central nervous system (CNS).\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"Pancreatic Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ABBV-927","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: Budiglimab","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: modified FOLFIRINOX","description":"Intravenous (IV) Infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Phase 1b: Percentage of participants experiencing Adverse Events","time_frame":"Up to 6 months","description":"An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related."},{"outcome_type":"primary","measure":"Phase 1b: Number of Participants with Potentially Clinically Significant (PCS) Laboratory (Hematological and Chemistry) Values","time_frame":"Up to 6 months","description":"Baseline values and changes from baseline will be summarized for each scheduled post-baseline visit for laboratory data as applicable. If more than one measurement exists for a participant on a particular day and time, an arithmetic average will be calculated. This average will be that participant's measurement for that day. For participants that do not have any post-baseline measurements, only their baseline values will be summarized."},{"outcome_type":"primary","measure":"Phase 1b: Number of Participants with Potentially Clinically Significant (PCS) Vital Signs","time_frame":"Up to 6 months","description":"Baseline values and changes from baseline will be summarized for each scheduled post-baseline visit for vital signs data."},{"outcome_type":"primary","measure":"Phase 1b: Number of Participants with Dose Limiting Toxicities (DLT)","time_frame":"Up to 6 months","description":"A DLT is defined as any serious AE for which a clear alternative cause cannot be established (e.g., attributed to the disease under study, another disease, or to a concomitant medication [e.g., COVID-19 vaccine] by the investigator or AbbVie Therapeutic Area (TA) MD] that occurs during the DLT observation period, and is not listed as a predefined exception in the protocol."},{"outcome_type":"primary","measure":"Phase 2: Overall Survival","time_frame":"48 months.","description":"Overall survival is defined as the time between the date of randomization and death due to any cause."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Maximum Plasma Concentration (Cmax)","time_frame":"Up to approximately 3 months","description":"The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Time to Maximum Observed Plasma Concentration (Tmax)","time_frame":"Up to approximately 3 months","description":"The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Area Under the Concentration-time Curve Over the Time Interval (AUC) in Plasma","time_frame":"Up to approximately 3 months.","description":"The area under the plasma concentration-time curve (AUC; measured in ng*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Objective Response Rate (ORR)","time_frame":"Up to approximately 27 months","description":"ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) per investigator assessment according to RECIST version 1.1."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Clinical Benefit Rate (CBR)","time_frame":"Up to approximately 27 months","description":"Clinical Benefit Rate (CBR) is defined as the percentage of participants whose best overall response is either Complete Response (CR), Partial Response (PR), or stable disease (SD) according to RECIST version 1.1."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Duration of Response (DOR) for Participants Who Achieve a Documented Confirmed Response of CR/PR","time_frame":"Up to approximately 27 months","description":"DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Progression Free Survival (PFS)","time_frame":"Up to approximately 24 months after study drug discontinuation","description":"PFS is defined as the time from randomization to a documented radiographic disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, clinical progression or death from any cause, whichever occurs earlier."},{"outcome_type":"secondary","measure":"Phase 1b and Phase 2: Quality of Life(QoL)-Measure Participant Overall Perceptions of Their Change in Pancreatic Cancer Symptoms includes the Patient Global Impression of Severity (PGIS) and the the Patient Global Impression of Change (PGIC)","time_frame":"Up to approximately 25 months","description":"Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) will measure participants' overall perceptions of their pancreatic cancer symptoms over time."},{"outcome_type":"secondary","measure":"Phase 2: Percentage of Participants Experiencing Adverse Events","time_frame":"Up to approximately 27 months.","description":"An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment."}]}
{"nct_id":"NCT04854668","start_date":"2021-05-27","phase":"Phase 3","enrollment":698,"brief_title":"A Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer","official_title":"A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer","primary_completion_date":"2024-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-08-18","description":"This is an open label, randomized, phase  study to treat subjects with RAS/BRAF wild-type, unresectable metastatic colorectal cancer. The patients will be randomized into two arms consist of Anlotinib (3 weeks/cycle) + CapeOx and Bevacizumab (3 week/cycle) + CapeOx at a ratio of 1:1. This study is conducted to assess the efficacy and safety of Anlotinib and Chemotherapy as first-line treatment in subjects with RAS/BRAF wild-type Metastatic Colorectal Cancer.","other_id":"ALTN--02","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Understood and Signed an informed consent form. 2. Eastern Cooperative Oncology\r\n             Group (ECOG) performance status of 0 to 1Life expectancy 3 months.\r\n\r\n             3. Histologically or cytologically confirmed unresectable metastatic colorectal\r\n             cancer.\r\n\r\n             4. Has RAS/BRAF wild-type. 5. Has at least one measurable lesion. 6. Adequate organ\r\n             function. 7.Male or female subjects should agree to use an adequate method of\r\n             contraception starting with the first dose of study therapy through 6 months after the\r\n             last dose of study (such as intrauterine devices , contraceptives or condoms) ; No\r\n             pregnant or breastfeeding women, and a negative pregnancy test are received within 7\r\n             days before the randomization.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  1.Has dMMR/MSI-H. 2. Combined with the following diseases or medical history:\r\n\r\n               1. Previous or co-existing malignancies within 3 years except for cured cervical\r\n                  carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors\r\n\r\n               2. Has many factors that affect the oral administration of drugs\r\n\r\n               3. Has Gastrointestinal bleeding or perforation within 4 weeks before the first\r\n                  dose\r\n\r\n               4. Has active inflammatory bowel disease within 4 weeks before the first dose\r\n\r\n               5. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated\r\n                  drainage\r\n\r\n               6. Patients whose adverse events (except hair loss) caused by previous treatment did\r\n                  not recover to CTCAE 1 degree\r\n\r\n               7. Has received major surgical procedurebiopsy or obvious traumatic injury within\r\n                  28 days before the first dose\r\n\r\n               8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary\r\n                  of blood vessels is unclear\r\n\r\n               9. Has any bleeding event or the level of bleeding events  CTCAE 3\r\n\r\n              10. Has unhealed wounds, ulcerative or fractures\r\n\r\n              11. Has arterial or venous thromboembolic events occurred within 6 months, such as\r\n                  cerebrovascular accident (including transient ischemic attack), deep vein\r\n                  thrombosis and pulmonary embolism\r\n\r\n              12. Has a history of psychotropic substance abuse and are unable to quit \r\n\r\n              13. Has any severe and / or uncontrolled disease 3.Tumor related symptoms and\r\n                  treatment\r\n\r\n               1. Has received chemotherapy, surgery, radiotherapy, and other anti-cancer therapy\r\n                  within 4 weeks before the first dose.\r\n\r\n               2. Has received anti-tumor Chinese patent medicine which were approved by NMPA\r\n                  Within 2 weeks before the first dose.\r\n\r\n               3. Previous adjuvant therapy containing anti-vascular or anti-EGFR targeted drugs.\r\n\r\n               4. Has received systematic treatment for advanced colorectal cancer.\r\n\r\n               5. Has symptomatic brain metastases or control of symptoms < 2 month. 4.Has\r\n                  participated in other anticancer drug clinical trials within 4 weeks. 5.According\r\n                  to the judgement of the researchers, there are other factors that may lead to the\r\n                  termination of the study.\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Anlotinib hydrochloride capsule","description":"Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)"},{"intervention_type":"Drug","name":"Drug: Bevacizumab","description":"Bevacizumab 7.5mg/kg, intravenous drip, on Day 1"},{"intervention_type":"Drug","name":"Drug: Oxaliplatin","description":"Oxaliplatin 130mg/m2, intravenous drip, on Day 1"},{"intervention_type":"Drug","name":"Drug: Capecitabine","description":"Capecitabine 850mg/m2 administrated orally twice daily from Day 1-14."}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) assessed by IRC","time_frame":"Baseline up to 15 months","description":"PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"Baseline up to 15 months","description":"PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Baseline up to 20 months","description":"OS defined as the time from the first dose to death from any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up."},{"outcome_type":"secondary","measure":"Objective Response Rate（ORR）","time_frame":"Baseline up to 15 months","description":"Percentage of subjects achieving complete response (CR) and partial response (PR) ."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Baseline up to 15 months","description":"Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD)."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Baseline up to 15 months","description":"DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first."}]}
{"nct_id":"NCT04795713","start_date":"2021-05-27","phase":"Phase 1","enrollment":138,"brief_title":"Study of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1","official_title":"A Phase 1 Open-label, Multicenter, Dose-ranging Study to Investigate Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1","primary_completion_date":"2025-04-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-05-31","last_update":"2021-09-09","description":"This will be a Phase 1 Open-label, dose escalation and expansion study of MT-6402 (an Engineered Toxin Body (ETB)) in subjects with advanced solid cancer that expresses PD-L1","other_id":"MT-6402-001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Part A\r\n\r\n          1. Subject must be at least 18 years old and must have histologically confirmed,\r\n             unresectable, locally advanced, or metastatic PD-L1-expressing solid cancer not\r\n             amenable to standard treatment, or standard treatment is not available, or in the\r\n             Investigator's opinion the standard treatment would not be in the subject's best\r\n             interest. Any level of PD-L1 expression assessed by using any Food and Drug\r\n             Administration (FDA) approved PD-L1 immunohistochemistry (IHC) assay is accepted. The\r\n             assessment should have been performed on the most recent available tissue from a site\r\n             of metastatic disease (if possible).\r\n\r\n          2. Subject must have evaluable or measurable disease.\r\n\r\n        Part B\r\n\r\n          1. Subject must be at least 18 years old and must have histologically confirmed,\r\n             unresectable, locally advanced or metastatic PD-L1-expressing solid cancer (defined\r\n             below) not amenable to standard treatment, or standard treatment is not available, or\r\n             in the Investigator's opinion the standard treatment would not be in the subject's\r\n             best interest. PD-L1 expression must be assessed at screening by the study's central\r\n             laboratory, using VENTANA SP263 PD-L1 assay on a tissue from a site of metastatic\r\n             disease (if possible). For this purpose, recent archived tissue suitable for PD-L1\r\n             expression assessment by IHC (obtained after the last treatment and within 6 months)\r\n             or fresh biopsy material can be used. The PD-L1 assessment must show at least 5% vCPS\r\n             (visually estimated Combined Positive Score) for eligibility.\r\n\r\n               -  Arm 1: Histologically confirmed recurrent or metastatic NSCLC not amenable to\r\n                  standard treatment, or standard treatment is not available, or in the\r\n                  Investigator's opinion the standard treatment would not be in the subject's best\r\n                  interest. NOTE: subjects with driver mutations are only eligible if they have\r\n                  received all appropriate targeted therapies.\r\n\r\n               -  Arm 2: Histologically confirmed recurrent or metastatic SCCHN (oral cavity,\r\n                  oropharynx, hypopharynx, or larynx) not amenable to standard treatment, or\r\n                  standard treatment is not available, or in the Investigator's opinion the\r\n                  standard treatment would not be in the subject's best interest. Subjects who\r\n                  refuse radical resection are eligible. NOTE: squamous cell carcinoma of any other\r\n                  primary anatomic location in the head and neck, subjects with SCCHN of unknown\r\n                  primary, and subjects with skin squamous cell carcinoma (SCC) of the head and\r\n                  neck are not eligible for this arm. The tumor must be platinum resistant or the\r\n                  subject ineligible for platinum therapy due to hypersensitivity or concerns with\r\n                  ototoxicity.\r\n\r\n               -  Arm 3: Subjects with any other relapsed or refractory PD-L1 positive solid tumor\r\n                  not amenable to standard treatment, or standard treatment is not available, or in\r\n                  the Investigator's opinion the standard treatment would not be in the subject's\r\n                  best interest, who received PD-1/PD-L1 treatment. Subjects with PD-L1 positive\r\n                  solid tumor types, for which PD-1/PD-L1 treatment is not approved, could be\r\n                  enrolled at the Investigator's discretion and after discussion with the Medical\r\n                  Monitor.\r\n\r\n          2. Subject must have at least 1 measurable tumor lesion according to RECIST 1.1.\r\n\r\n             Parts A and B\r\n\r\n          3. Subject must have Eastern Cooperative Oncology Group (ECOG) performance score of 0 or\r\n             1.\r\n\r\n          4. Prior treatment must include a CPI (i.e., PD-1 inhibitors, PD-L1 inhibitors with or\r\n             without CTLA-4 inhibitors) if there is an approved CPI for the specific cancer type.\r\n             Subjects may also have received CPIs in an investigational setting. Subjects who have\r\n             not received a CPI and where there is no approved CPI for the specific cancer type\r\n             could be enrolled at the Investigator's discretion and after discussion with the\r\n             Medical Monitor.\r\n\r\n          5. Subject must have adequate bone marrow function (NOTE: administration of blood\r\n             products and growth factors is not allowed within 2 weeks prior to screening\r\n             laboratory tests):\r\n\r\n               -  absolute neutrophil count (ANC)  1,500/L\r\n\r\n               -  platelet count  100,000/L\r\n\r\n               -  hemoglobin  8.0 g/dL\r\n\r\n          6. Subject must have adequate renal function, based on estimated creatinine clearance\r\n             (eCrCl)  50 mL/min, calculated by the Cockcroft-Gault equation.\r\n\r\n             NOTE: At the Investigator's discretion, the eCrCl result < 50 mL/min may be verified\r\n             by measured creatinine clearance (mCrCl) based on the 24-hour urine collection.\r\n             Subjects with mCrCl  50 mL/min will be eligible irrespective of the eCrCl result\r\n             calculated by the Cockcroft-Gault equation.\r\n\r\n          7. Subject must have adequate hepatic function, as determined by:\r\n\r\n               -  total bilirubin (or direct bilirubin for subjects with Gilbert's disease) < 1.5 \r\n                  upper limit of normal (ULN)\r\n\r\n               -  aspartate aminotransferase (AST)  3  ULN (or  5  ULN if liver metastasis)\r\n\r\n               -  alanine aminotransferase (ALT)  3  ULN (or  5  ULN if liver metastasis)\r\n\r\n          8. Subject must have adequate serum albumin (albumin  2.5 g/dL)\r\n\r\n          9. Women of reproductive potential must have a negative highly sensitive pregnancy test\r\n             within 72 hours before the start of treatment. Women who are postmenopausal (> 1 year\r\n             since last menstrual cycle) or permanently sterilized (e.g., bilateral tubal\r\n             occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of\r\n             reproductive potential.\r\n\r\n         10. Subjects of reproductive potential must agree either to abstain continuously from\r\n             heterosexual intercourse or to use a highly effective birth control method from\r\n             signing the informed consent until 30 days after the last dose of MT-6402 for females\r\n             and until 90 days after the last dose of MT-6402 for males.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Part A\r\n\r\n        1. Subjects without available tissue from a site of metastatic disease or easily biopsiable\r\n        lesion (biopsy sites of non significant risk, in the opinion of the Investigator) or\r\n        unwilling to consent to biopsy.\r\n\r\n        Part B\r\n\r\n          1. Subjects without easily biopsiable lesions (biopsy sites of non significant risk, in\r\n             the opinion of the Investigator) or unwilling to consent to biopsy.\r\n\r\n             Parts A and B\r\n\r\n          2. History or current evidence of another neoplastic disease, except cervical carcinoma\r\n             in situ, superficial noninvasive bladder tumors, curatively treated Stage I to II non\r\n             melanoma skin cancer or any previous cancer curatively treated > 2 years before the\r\n             start of treatment.\r\n\r\n          3. Active autoimmune disease currently under treatment or required systemic treatment\r\n             within 2 years (replacement therapy, e.g., thyroxine, insulin, or physiologic\r\n             corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed).\r\n             Subjects who have not required systemic treatment of an auto-immune disease for at\r\n             least 2 years may be enrolled if permission is provided after discussion with the\r\n             Medical Monitor.\r\n\r\n          4. Ongoing > Grade 1 immune related toxicity caused by prior CPI therapy (i.e., PD-1\r\n             inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors). Subjects with stable\r\n             endocrinological AEs, e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or\r\n             diabetes mellitus, must have been on a stable dose of supplemental therapy for at\r\n             least 2 weeks before screening to be eligible for this study.\r\n\r\n          5. Evidence of active noninfectious  Grade 2 pneumonitis or current evidence of  Grade\r\n             3 other underlying pulmonary disease.\r\n\r\n          6. Received any of the following PD-L1 inhibitors within the following time periods prior\r\n             to the first dose of MT-6402: atezolizumab - 12 months; durvalumab - 7 months;\r\n             avelumab - 2 months.\r\n\r\n          7. Any concurrent cancer treatment, apart from local treatment of non-target lesions for\r\n             palliative intent (e.g., local surgery or radiotherapy).\r\n\r\n          8. Prior radiation therapy within 4 weeks before the start of study treatment. NOTE: A\r\n             lesion in a previously irradiated area can only be considered target lesion if there\r\n             has been radiographical disease progression since the end of radiation therapy.\r\n\r\n          9. Received approved or investigational treatment for the disease under study (except PD\r\n             L1 inhibitors where exclusion criterion 6 applies) within 4 weeks before the start of\r\n             treatment. For small molecules (MW < 0.9 kDa), the washout is 5 half-lives, but at\r\n             least 2 weeks.\r\n\r\n         10. Subjects who have had allogeneic tissue or solid organ transplantation.\r\n\r\n         11. Current evidence of new or growing central nervous system (CNS) metastases during\r\n             screening. Subjects with known asymptomatic CNS metastases will be eligible if they\r\n             meet all the following criteria:\r\n\r\n               1. Had radiotherapy or another appropriate therapy for the CNS metastases.\r\n\r\n               2. Have stable CNS disease on the computed tomography (CT) or magnetic resonance\r\n                  imaging (MRI) scan within 4 weeks before screening compared with prior neuro\r\n                  imaging.\r\n\r\n         12. Major surgical procedure (as defined by the Investigator) within 28 days prior to the\r\n             start of study treatment.\r\n\r\n         13. History or current evidence of significant cardiovascular disease before the start of\r\n             treatment, including but not limited to the following conditions:\r\n\r\n               1. Angina pectoris requiring anti-anginal medication, (chest pain: Common\r\n                  Terminology Criteria for Adverse Events [CTCAE] Grade  2)\r\n\r\n               2. Clinically significant valvular disease.\r\n\r\n               3. Myocardial infarction within 12 months prior to the start of treatment.\r\n\r\n               4. Arterial thrombosis or pulmonary embolism within 3 months before the start of\r\n                  treatment.\r\n\r\n               5. History of Grade  2 symptomatic congestive heart failure (CHF) or New York Heart\r\n                  Association (NYHA) criteria Class  II.\r\n\r\n               6. Left ventricular ejection fraction (LVEF) < 55%, assessed preferably by\r\n                  echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan if ECHO is not\r\n                  available, within 28 days before starting study treatment.\r\n\r\n               7. High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate >\r\n                  100/min at rest and upon repeated testing, significant ventricular arrhythmia\r\n                  (CTCAE Grade  2 [ventricular tachycardia], or higher-grade atrioventricular\r\n                  [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block])\r\n                  or left ventricular bundle branch block. Subjects receiving digoxin, calcium\r\n                  channel blockers, or beta adrenergic blockers are eligible at the Investigator's\r\n                  discretion after consultation with the Medical Monitor if the dose has been\r\n                  stable for  2 weeks before the start of treatment with MT-6402.\r\n\r\n               8. Any of the following within 3 months before the start of treatment: pericarditis\r\n                  (any CTCAE Grade), pericardial effusion (CTCAE Grade  2), non-malignant pleural\r\n                  effusion (CTCAE Grade  2) or malignant pleural effusion (CTCAE Grade  3)\r\n                  (subjects with pleural effusion that is manageable and stable > 3 months prior to\r\n                  study are eligible).\r\n\r\n               9. QT interval correction for heart rate using Fridericia's formula (QTcF)  470 ms\r\n                  (average from 3 QTcF values on the triplicate 12-lead electrocardiogram [ECG]) at\r\n                  screening. In subjects with right bundle branch blocks, additional corrections\r\n                  will be performed to calculate the QT equivalent JT, and depending on the result\r\n                  the subject may be eligible with the agreement of the Medical Monitor.\r\n\r\n         14. Current evidence of uncontrolled human immunodeficiency virus (HIV), hepatitis B virus\r\n             (HBV), or hepatitis C virus (HCV) at screening. Serology testing is not required if\r\n             seronegativity is documented in the medical history, and if there are no clinical\r\n             signs suggestive of HIV or hepatitis infections, or suspected exposure. The following\r\n             exceptions apply for subjects with positive viral serology:\r\n\r\n               1. Subjects with HIV and an undetectable viral load and CD4 + T-cell (CD4+) counts \r\n                  350 cells/mL may be enrolled, but must be taking appropriate opportunistic\r\n                  infection prophylaxis, if clinically relevant.\r\n\r\n               2. Subjects with positive HBV serology are eligible if they have an undetectable\r\n                  viral load and the subject will receive antiviral prophylaxis for potential HBV\r\n                  reactivation per institutional guidelines.\r\n\r\n               3. Subjects with positive HCV serology are eligible if quantitative polymerase chain\r\n                  reaction (PCR) for plasma HCV RNA is below the lower limit of detection.\r\n                  Concurrent antiviral HCV treatment per institutional guidelines is allowed.\r\n\r\n         15. Current treatment requiring systemic steroids at doses > 10 mg/day prednisone\r\n             equivalent.\r\n\r\n         16. Subjects with a history of hypersensitivity or serious toxic reactions to kanamycin or\r\n             other aminoglycosides.\r\n\r\n         17. Subjects with unintentional weight loss > 10% of their body weight over the preceding\r\n             2 months or less before screening.\r\n\r\n         18. Female subjects who are pregnant or breastfeeding.\r\n\r\n         19. History or evidence of any other clinically significant disorder, condition or disease\r\n             (with the exception of those outlined above) that, in the opinion of the Investigator\r\n             or Medical Monitor, if consulted, would pose a risk to subject safety or interfere\r\n             with the study evaluation, procedures or completion.\r\n      ","sponsor":"Molecular Templates, Inc.","sponsor_type":"Industry","conditions":"Advanced Solid Tumor|Non-small Cell Lung Cancer|Squamous Cell Carcinoma of Head and Neck","interventions":[{"intervention_type":"Drug","name":"Drug: MT-6402","description":"Experimental Treatment"}],"outcomes":[{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Volume of distribution of steady-state (Vss)"},{"outcome_type":"primary","measure":"Evaluate the safety of MT-6402 in subjects with advanced cancer (solid tumors) and to estimate the maximum tolerated dose (MTD)","time_frame":"28 days (Part 1)","description":"Safety as measured by number of subjects with incidence of adverse events using CTCAE v4.0"},{"outcome_type":"primary","measure":"Evaluate the tolerability of MT-6402 in subjects with advanced cancer (solid tumors) and to estimate the maximum tolerated dose (MTD)","time_frame":"28 days (Part 1)","description":"Tolerability as measured by incidence of adverse events using CTCAE v4.0 and incidence of laboratory abnormalities"},{"outcome_type":"primary","measure":"Confirm the recommended Phase 2 dose (RP2D)","time_frame":"28 days (Part 2)","description":"Incidence of Adverse Events (AEs)"},{"outcome_type":"primary","measure":"Evaluate efficacy of MT-6402 in subjects with advanced cancer by objective response rate (ORR) with RECIST 1.1","time_frame":"up to 2 years (Part 2)","description":"ORR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria"},{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Maximum observed plasma concentration (Cmax)"},{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Time of maximum observed plasma concentration (tmax)"},{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t)"},{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Interpolated AUC to infinity (AUC0-∞)"},{"outcome_type":"secondary","measure":"Characterize the PK profile of MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Clearance (CL)"},{"outcome_type":"secondary","measure":"Evaluate efficacy of MT-6402 in subjects with advanced cancer by ORR with RECIST 1.1","time_frame":"up to 2 years (Part 1)","description":"ORR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria"},{"outcome_type":"secondary","measure":"Assess additional efficacy parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Duration of response (DOR)"},{"outcome_type":"secondary","measure":"Assess additional efficacy parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Progression-free survival (PFS)"},{"outcome_type":"secondary","measure":"Assess additional efficacy parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Overall Survival (OS)"},{"outcome_type":"secondary","measure":"Evaluate the immunogenicity of MT-6402 in subjects with advanced cancer","time_frame":"28 days (Parts 1 and 2)","description":"Anti-drug antibodies (ADA)"},{"outcome_type":"other","measure":"Evaluate the immunogenicity of MT-6402 in subjects with advanced cancer","time_frame":"28 days (Parts 1 and 2)","description":"Neutralizing antibodies (NAb)"},{"outcome_type":"other","measure":"Explore efficacy of MT-6402 in subjects with advanced cancer by using ORR","time_frame":"up to 2 years (Part 2)","description":"ORR using immune-related RECIST (irRECIST)"},{"outcome_type":"other","measure":"Explore immune response to MT-6402 treatment","time_frame":"up to 2 years (Parts 1 and 2)","description":"Change from baseline in peripheral blood mononuclear cells and respective T cell subsets"},{"outcome_type":"other","measure":"Correlate the pharmacodynamic markers of cancer under study with tumor response to MT-6402 in subjects with advanced cancer","time_frame":"up to 2 years (Parts 1 and 2)","description":"Intensity of programmed death-ligand (PD-L1) expression by immunohistochemistry staining in biopsied metastatic tumor tissue (tumor cells, immune cells) and in circulating tumor and immune cell markers, correlating with tumor response"},{"outcome_type":"other","measure":"Explore pharmacodynamic effect of cytomegalovirus (CMV) antigen presentation","time_frame":"Baseline to Cycle 1 Day 15 (each cycle is 28 days) (Part 1)","description":"Change of CMV activated T cells in peripheral blood from baseline to Cycle 1 Day 15"},{"outcome_type":"other","measure":"Correlate pharmacodynamic effect of cytomegalovirus (CMV) antigen presentation with tumor response","time_frame":"Baseline to Cycle 1 Day 15 (each cycle is 28 days) (Part 2), Baseline and Cycle 2 (each cycle is 28 days) (Part 2)","description":"Change of CMV activated T cells in peripheral blood from baseline to Cycle 1 Day 15, Comparison of lymphocyte infiltration from metastatic tumor biopsy at baseline and Cycle 2"},{"outcome_type":"other","measure":"If warranted, evaluate the exposure-response relationship for MT-6402 via Pharmacokinetics (PK) parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Maximum observed plasma concentration (Cmax)"},{"outcome_type":"other","measure":"If warranted, evaluate the exposure-response relationship for MT-6402 via Pharmacokinetics (PK) parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Time of maximum observed plasma concentration (tmax)"},{"outcome_type":"other","measure":"If warranted, evaluate the exposure-response relationship for MT-6402 via Pharmacokinetics (PK) parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"The area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t)"},{"outcome_type":"other","measure":"If warranted, evaluate the exposure-response relationship for MT-6402 via Pharmacokinetics (PK) parameters","time_frame":"up to 2 years (Parts 1 and 2)","description":"Interpolated AUC to infinity (AUC0-∞)"},{"outcome_type":"other","measure":"Assess quality of life with MT-6402 treatment","time_frame":"up to 2 years (Parts 1 and 2)","description":"European Organization for the Research and Treatment of Cancer-quality of life questionnaire core 30 (EORTC-QLQ-C30) (Version 3). The Euro-Quality-of-Life-questionnaire C30 (Version 3) assesses five states (mobility, self care, usual activities, pain / discomfort, and anxiety / depression) at four different levels - Not at All (1), A Little (2), Quite a Bit (3), and Very Much (4)"}]}
{"nct_id":"NCT04934722","start_date":"2021-05-25","phase":"Phase 3","enrollment":186,"brief_title":"Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension","official_title":"A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)","primary_completion_date":"2028-01-07","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2028-01-07","last_update":"2021-09-08","description":"This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in Chinese participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS).","other_id":"3475-991 China Extension","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Male participants with histologically- or cytologically-confirmed adenocarcinoma of\r\n             the prostate without small cell histology\r\n\r\n          -  Has metastatic disease assessed by investigator and verified by BICR by either 2 bone\r\n             lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance\r\n             imaging (CT/MRI)\r\n\r\n          -  Willing to maintain continuous ADT with a LHRH agonists or antagonists during study\r\n             treatment or have a history of bilateral orchiectomy\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed\r\n             within 10 days of randomization\r\n\r\n          -  Participants receiving bone resorptive therapy (including, but not limited to,\r\n             bisphosphonate or denosumab) must have been on stable doses prior to randomization\r\n\r\n          -  Has adequate organ function\r\n\r\n          -  Has provided newly obtained core or excisional biopsy (obtained within 12 months of\r\n             screening) from soft tissue not previously irradiated (samples from tumors progressing\r\n             in a prior site of radiation are allowed). Participants with bone only or bone\r\n             predominant disease may provide a bone biopsy sample\r\n\r\n          -  Male participants must agree to the following during the intervention period and for\r\n             at least 120 days after the last dose of study intervention: Refrain from donating\r\n             sperm PLUS either be abstinent from heterosexual intercourse and agree to remain\r\n             abstinent OR agree to use contraception, unless confirmed to be azoospermic\r\n\r\n          -  Male participants must agree to use male condom when engaging in any activity that\r\n             allows for passage of ejaculate to another person of any sex\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             in the last 3 years\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n\r\n          -  Has undergone major surgery including local prostate intervention (excluding prostate\r\n             biopsy) within 28 days prior to randomization and not recovered adequately from the\r\n             toxicities and/or complications\r\n\r\n          -  Has a gastrointestinal disorder affecting absorption or is unable to swallow\r\n             tablets/capsules\r\n\r\n          -  Has an active infection (including tuberculosis) requiring systemic therapy\r\n\r\n          -  Has a history of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or\r\n             hepatitis C virus (HCV) infection\r\n\r\n          -  Has known or suspected central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis\r\n\r\n          -  Has a history of seizure or any condition that may predispose to seizure\r\n\r\n          -  Has a history of loss of consciousness within 12 months of screening\r\n\r\n          -  Has had myocardial infarction or uncontrolled angina within 6 months prior to\r\n             randomization, or has New York Heart Association class III or IV congestive heart\r\n             failure or a history of New York Heart Association class III or IV congestive heart\r\n             failure\r\n\r\n          -  Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or\r\n             uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood\r\n             pressure >105 mmHg) at the screening visit\r\n\r\n          -  Has a history of clinically significant ventricular arrhythmias\r\n\r\n          -  Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their\r\n             excipients\r\n\r\n          -  Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate\r\n             cancer for >39 months in duration or within 9 months prior to randomization or with\r\n             evidence of disease progression while receiving ADT\r\n\r\n          -  Has had prior treatment with a next generation hormonal agent (eg, abiraterone,\r\n             enzalutamide, apalutamide, darolutamide)\r\n\r\n          -  Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),\r\n             anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent\r\n             directed to another stimulatory or coinhibitory T-cell receptor\r\n\r\n          -  Has received a live vaccine within 30 days prior to randomization\r\n\r\n          -  Has a \"superscan\" bone scan\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n\r\n          -  Is expecting to conceive or father children within the projected duration of the\r\n             study, starting with the screening visit through 120 days after the last dose of study\r\n             treatment\r\n\r\n          -  Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic\r\n             prostate cancer with the following exceptions:\r\n\r\n               1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation\r\n                  antiandrogens, if patient was not treated with docetaxel\r\n\r\n               2. May have 1 course of palliative radiation or surgical therapy to treat symptoms\r\n                  resulting from metastatic disease if it was administered at least 4 weeks prior\r\n                  to randomization\r\n\r\n               3. For participants with low volume metastatic disease, may have 1 course of\r\n                  definitive radiotherapy if it was administered at least 4 weeks prior to\r\n                  randomization\r\n\r\n               4. Up to 6 cycles of docetaxel therapy with final treatment administration completed\r\n                  within 2 months of randomization and no evidence of disease progression. In these\r\n                  participants up to 6 months of ADT permitted\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Metastatic Hormone-Sensitive Prostate Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles."},{"intervention_type":"Drug","name":"Drug: Enzalutamide","description":"Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met."},{"intervention_type":"Procedure","name":"Procedure: Androgen Deprivation Therapy (ADT)","description":"Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label."},{"intervention_type":"Other","name":"Other: Placebo","description":"Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles."}],"outcomes":[{"outcome_type":"primary","measure":"Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review","time_frame":"Up to approximately 77 months","description":"rPFS is defined as the time from randomization to radiographic progression, or death due to any cause, whichever occurs first. rPFS according to PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm."},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 77 months","description":"OS is defined as the time from randomization to death due to any cause. OS will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)","time_frame":"Up to approximately 77 months","description":"TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever comes first. TFST will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time to Symptomatic Skeletal-Related Event (TTSSRE)","time_frame":"Up to approximately 77 months","description":"TTSSRE is defined as the time from randomization to the first Symptomatic Skeletal-Related Event (SSRE), defined as use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. TTSSRE will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time to Prostate-specific Antigen (PSA) Progression","time_frame":"Up to approximately 77 months","description":"Time to PSA progression is defined as the time from randomization to PSA progression. The PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA progression will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review","time_frame":"Up to approximately 77 months","description":"Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression, and will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (\"Worst Pain in 24 Hours\") and Opiate Use","time_frame":"Up to approximately 77 months","description":"TTPP is defined as the time from randomization to pain progression. In this study, pain progression will be assessed by participant responses to Item 3 of the BPI-SF (\"worst pain in 24 hours\") and by participant opiate use, and will be reported for each study arm."},{"outcome_type":"secondary","measure":"Time from Randomization to Disease Progression as Determined by Investigator Assessment after Next-line of Therapy or Death from Any Cause, Whichever Occurs First (PFS2)","time_frame":"Up to approximately 77 months","description":"PFS2 is defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first. PFS2 will be reported for each study arm."},{"outcome_type":"secondary","measure":"Prostate-specific Antigen (PSA) Response Rate","time_frame":"Up to approximately 77 months","description":"PSA response rate is defined as the percentage of participants in the analysis population with PSA decline of ≥50% from baseline measured twice at least 3 weeks apart, and will be reported for each study arm."},{"outcome_type":"secondary","measure":"Prostate-specific antigen (PSA) Undetectable Rate","time_frame":"Up to approximately 77 months","description":"PSA undetectable rate is defined as the percentage of participants in the analysis population with PSA < 0.2 ng/mL during study intervention, and will be reported for each study arm."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review","time_frame":"Up to approximately 77 months","description":"ORR is defined as the percentage of participants in the analysis population who have a best overall response of either confirmed CR or PR. ORR per PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review","time_frame":"Up to approximately 77 months","description":"DOR is defined as the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever occurs first. DOR per PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm."},{"outcome_type":"secondary","measure":"Number of Participants Who Experience an Adverse Event (AE)","time_frame":"Up to approximately 77 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported for each arm."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)","time_frame":"Up to approximately 77 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm."}]}
{"nct_id":"NCT04810078","start_date":"2021-05-24","phase":"Phase 3","enrollment":454,"brief_title":"A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread","official_title":"A Phase 3, Open-label, Randomized, Noninferiority Trial of Subcutaneous Formulation of Nivolumab Versus Intravenous Nivolumab in Participants With Advanced or Metastatic Clear Cell Renal Cell Carcinoma Who Have Received Prior Systemic Therapy","primary_completion_date":"2023-12-13","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-01-29","last_update":"2021-07-26","description":"The purpose of this study is to evaluate the drug levels, efficacy, safety, and tolerability of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread.","other_id":"CA209-67T","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Histological confirmation of renal cell carcinoma (RCC) with a clear cell component,\r\n             including participants who may also have sarcomatoid features\r\n\r\n          -  Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC\r\n             (Stage IV)\r\n\r\n          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST)\r\n             v1.1 criteria within 28 days prior to randomization\r\n\r\n          -  Received no more than 2 prior systemic treatment regimens\r\n\r\n          -  Intolerance or progression on or after the last treatment regimen received and within\r\n             6 months prior to randomization on the study\r\n\r\n          -  Karnofsky PS  70 at screening\r\n\r\n          -  Must agree to follow specific methods of contraception, if applicable\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Untreated, symptomatic central nervous system (CNS) metastases\r\n\r\n          -  Concurrent malignancy (present during screening) requiring treatment or history of\r\n             prior malignancy active within 2 years prior to randomization\r\n\r\n          -  Active, known, or suspected autoimmune disease\r\n\r\n          -  Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency\r\n             syndrome (AIDS) defining opportunistic infection within the last year, or a current\r\n             CD4 count < 350 cells/L. Participants with HIV are eligible if:\r\n\r\n               1. They have received established antiretroviral therapy (ART) for at least 4 weeks\r\n                  prior to randomization\r\n\r\n               2. They continue on ART as clinically indicated while enrolled on study\r\n\r\n               3. CD4 counts and viral load are monitored per standard of care by a local health\r\n                  care provider\r\n\r\n               4. Inclusion of participants with HIV should be based on Investigator clinical\r\n                  judgment in consultation with the Medical Monitor NOTE: Testing for HIV must be\r\n                  performed at sites where mandated locally. HIV-positive participants must be\r\n                  excluded where mandated locally\r\n\r\n          -  Serious or uncontrolled medical disorders including for example, active severe acute\r\n             respiratory syndrome coronavirus 2 (SAR-CoV-2) infection within approximately 4 weeks\r\n             prior to screening. In the case of prior SARS-CoV-2 infection, acute symptoms must\r\n             have resolved based on investigator clinical judgment and, in consultation with\r\n             Medical Monitor, there are no sequelae that would place the participant at a higher\r\n             risk of receiving investigational treatment to be eligible\r\n\r\n          -  Prior treatment with an programmed death receptor-1 (anti-PD-1), programmed death\r\n             ligand-1 (anti-PD-L1), or cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4)\r\n             antibody, or any other antibody or drug specifically targeting T-cell costimulation or\r\n             checkpoint pathways\r\n\r\n          -  Treatment with any live attenuated vaccine within 30 days of first study treatment\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Clear Cell Renal Cell Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: Nivolumab and rHuPH20","description":"Specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: Nivolumab","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"secondary","measure":"Trough serum concentration at day 28 (Cmind28)","time_frame":"At 28 days"},{"outcome_type":"secondary","measure":"Maximum serum concentration after the first dose (Cmax1)","time_frame":"Up to 7 days"},{"outcome_type":"secondary","measure":"Time to peak serum concentration after the first dose (Tmax1)","time_frame":"Up to 7 days"},{"outcome_type":"secondary","measure":"Peak serum concentration at steady-state (Cmaxss)","time_frame":"Up to 4 months"},{"outcome_type":"secondary","measure":"Steady-state average serum concentration (Cavgss)","time_frame":"Up to 4 months"},{"outcome_type":"secondary","measure":"Incidence of adverse events (AEs)","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Incidence of serious adverse events (SAEs)","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 2 years"},{"outcome_type":"primary","measure":"Time-averaged serum concentration over 28 days (Cavgd28)","time_frame":"Up to 28 days"},{"outcome_type":"secondary","measure":"Incidence of deaths","time_frame":"Up to 5 years"},{"outcome_type":"primary","measure":"Trough serum concentration at steady-state (Cminss)","time_frame":"Up to 4 months"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Incidence of clinically significant changes in clinical laboratory results: Hematology tests","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: DCR by BICR at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: DOR by BICR at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: TTR by BICR with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: TTR by BICR at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: PFS by BICR with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: PFS by BICR at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up","time_frame":"Up to 2 years 6 months"},{"outcome_type":"secondary","measure":"Efficacy parameters: OS with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: OS at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Efficacy parameters: ORR by BICR at end of study","time_frame":"Up to 5 years"},{"outcome_type":"secondary","measure":"Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Incidence of local injection- or infusion-site reactions","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Percentage of participants who develop anti-nivolumab antibodies, if applicable","time_frame":"Up to 2 years 3 months"},{"outcome_type":"secondary","measure":"Percentage of participants who develop neutralizing antibodies, if applicable","time_frame":"Up to 2 years 3 months"}]}
{"nct_id":"NCT04492488","start_date":"2021-05-24","phase":"Phase 1/Phase 2","enrollment":129,"brief_title":"A Study of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer","official_title":"An Open-Label, Multi-center Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Efficacy and Pharmacokinetics of MRG002 in Patients With HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-08-31","last_update":"2021-09-02","description":"The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG002, as well as the immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG002 in patients with HER2-positive advanced solid tumors and locally advanced or metastatic gastric/gastroesophageal junction (GEJ) cancer.","other_id":"MRG002-101","allocation":"Non-Randomized","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  The patient must be able to provide written informed consent and follow the\r\n             requirements specified in protocol.\r\n\r\n          -  Age: 18 years.\r\n\r\n          -  Life expectancy 6 months.\r\n\r\n          -  Must have histologically or cytologically confirmed HER2-positive metastatic,\r\n             unresectable cancer and must have had prior disease progression on all standard\r\n             therapies for their tumor.\r\n\r\n          -  Available archival tumor tissue (archival or from a new biopsy).\r\n\r\n          -  At least one non-irradiated measurable tumor lesion according to RECIST v1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Acceptable liver, renal, hematologic and coagulation function.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Toxicities (except alopecia & fatigue) due to prior antitumor therapy are higher than\r\n             CTCAE v5.0 Grade 1.\r\n\r\n          -  Toxicities due to radiotherapy (higher than grade 1) have not resolved to CTCAE v5.0\r\n             Grade 1 at least 21 days prior to the screening visit.\r\n\r\n          -  Prior palliative or therapeutic radiation therapy to any RECIST v1.1 target lesion\r\n             that defines baseline measurable disease for the study.\r\n\r\n          -  Untreated or uncontrolled central nervous system (CNS) metastases.\r\n\r\n          -  Any chemotherapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy\r\n             within 3 weeks of the first dose of study treatment.\r\n\r\n          -  Any severe cardiac dysfunction within 6 months of enrollment.\r\n\r\n          -  Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of\r\n             study drug.\r\n\r\n          -  Concurrent malignancy within 5 years prior to entry.\r\n\r\n          -  Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood\r\n             pressure > 100 mmHg).\r\n\r\n          -  History of ventricular tachycardia, or torsade des pointes.\r\n\r\n          -  History of moderate to severe dyspnea at rest due to advanced malignancies or their\r\n             complications, severe primary lung disease, current need of continuous oxygen therapy,\r\n             or clinically active interstitial lung disease (ILD) or pneumonitis.\r\n\r\n          -  Major surgery within 4 weeks of the first dose of study treatment and not fully\r\n             recovered. Minor surgery within 2 weeks prior to study treatment.\r\n\r\n          -  Known allergic reactions to any component or excipient of MRG002 or known allergic\r\n             reactions to trastuzumab or other prior anti-HER2 or other monoclonal antibody  Grade\r\n             3.\r\n\r\n          -  Patients who have any known liver disease, including chronic hepatitis B, hepatitis C,\r\n             autoimmune hepatic disorders, primary biliary cirrhosis or sclerosing cholangitis;\r\n             Patients who have concurrent, serious, uncontrolled infections or known infection with\r\n             HIV, or have a diagnosed acquired immunodeficiency syndrome (AIDS); or an uncontrolled\r\n             autoimmune disease, or have undergone organ transplant.\r\n\r\n          -  Active uncontrolled bacterial, viral, fungal, rickettsial, or parasitic infection.\r\n\r\n          -  Any severe and/or uncontrolled systemic disease that at the discretion of investigator\r\n             and sponsor makes it undesirable for the patient to participate in this study.\r\n\r\n          -  Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.\r\n\r\n          -  Use of strong CYP3A4 inhibitors.\r\n\r\n          -  Pregnancy or breast-feeding.\r\n      ","sponsor":"Shanghai Miracogen Inc.","sponsor_type":"Industry","conditions":"Advanced Solid Tumors|Advanced or Metastatic Gastric Cancer|Advanced or Metastatic Gastroesophageal Junction Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: MRG002","description":"Administrated intravenously"}],"outcomes":[{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD)","time_frame":"DLT will be evaluated during the first 21-day treatment cycle (Cycle 1)","description":"The dose level in which (i) less than 2 out of 6 patients in a treatment cohort experiences dose-limiting toxicity (DLT); or (ii) <33% of an evaluable patient treatment cohort experiences DLT."},{"outcome_type":"primary","measure":"Recommended Phase II Dose (RP2D)","time_frame":"Day 1 to Day 21 of Cycle 1","description":"Identify the recommended Phase II dose (RP2D) of MRG002 for Phase II clinical study. The RP2D may be the same as the MTD or an evaluable dose level lower than the MTD."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR)","time_frame":"Baseline to study completion (24 months)","description":"Objective response rate (ORR) will be assessed by Independent Central Review (ICR) based on RECIST v1.1. Cumulative safety and dosing data will be reviewed by an independent Data Safety Monitoring Board (DSMB)."},{"outcome_type":"primary","measure":"Incidence of Adverse Events (AEs)","time_frame":"After signing informed consent until 45 days after the last dose of MRG002","description":"AEs will be coded using MedDAR. Descriptive statistics will be used to summarize results to assess the safety and tolerability profile of MRG002."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Baseline to study completion (24 months)","description":"Sensitivity analyses of DoR from the Investigator's assessment will be performed in the final analysis."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Baseline to study completion (24 months)","description":"Sensitivity analyses of DCR from the Investigator's assessment will be performed in the final analysis."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"Baseline to study completion (24 months)","description":"Sensitivity analyses of PFS from the Investigator's assessment will be performed in the final analysis."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) parameter for MRG002: Maximum Drug Concentration (Cmax)","time_frame":"Baseline to study completion (24 months)","description":"Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"PK parameter for MRG002: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)","time_frame":"Baseline to study completion (24 months)","description":"AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"PK parameter for total antibody (TAb): Cmax","time_frame":"Baseline to study completion (24 months)","description":"Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"PK parameter for TAb: AUClast","time_frame":"Baseline to study completion (24 months)","description":"AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"PK parameter for Monomethyl Auristatin E (MMAE): Cmax","time_frame":"Baseline to study completion (24 months)","description":"Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"PK parameter for MMAE: AUClast","time_frame":"Baseline to study completion (24 months)","description":"AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statistics."},{"outcome_type":"secondary","measure":"Immunogenicity","time_frame":"Baseline to study completion (24 months)","description":"5 mL Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. The incidence of ADA will be summarized for all patients who received at least one administration of MRG002."}]}
{"nct_id":"NCT04704934","start_date":"2021-05-21","phase":"Phase 3","enrollment":490,"brief_title":"Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)","official_title":"A Phase 3, Multicenter, 2-Arm Randomized, Open-Label Study of Trastuzumab Deruxtecan in Subjects With HER2-Positive Metastatic and/or Unresectable Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)","primary_completion_date":"2024-04-15","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-11-15","last_update":"2021-09-10","description":"This study will evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with ramucirumab and paclitaxel (Ram + PTX) in participants with HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy.","other_id":"DS8201-A-U306","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Adults (according to local regulation) and able to provide informed consent for study\r\n             participation.\r\n\r\n          -  Pathologically documented gastric and GEJ adenocarcinoma that has been previously\r\n             treated in the metastatic setting (unresectable, locally advanced, or metastatic\r\n             disease).\r\n\r\n          -  Progression on or after first-line therapy with a trastuzumab or approved trastuzumab\r\n             biosimilar-containing regimen. Note: Prior adjuvant therapy with a\r\n             trastuzumab-containing regimen can be counted as a line of therapy if the subject\r\n             progressed on or within 6 months of completing adjuvant therapy.\r\n\r\n          -  Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification\r\n             by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or\r\n             after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1 at both Screening and\r\n             within 3 days prior to randomization.\r\n\r\n          -  Adequate bone marrow, renal, and hepatic function within 14 days of randomization.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Use of anticancer therapy after trastuzumab-containing treatment\r\n\r\n          -  Medical history of myocardial infarction (MI) within 6 months before\r\n             randomization/enrollment, symptomatic congestive heart failure (New York Heart\r\n             Association Class II to IV).\r\n\r\n          -  Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to >470 msec\r\n             (female subjects) or >450 msec (male subjects) based on average of the Screening\r\n             triplicate12-lead ECG.\r\n\r\n          -  Has a pleural effusion, ascites, or pericardial effusion that requires drainage,\r\n             peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART).\r\n             Drainage and CART must be at least 2 weeks prior to Screening.\r\n\r\n          -  Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that\r\n             required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis\r\n             cannot be ruled out by imaging at Screening.\r\n\r\n          -  Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis,\r\n             Sjgren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of)\r\n             pulmonary involvement at the time of Screening.\r\n\r\n          -  Prior pneumonectomy.\r\n\r\n          -  Spinal cord compression or clinically active central nervous system metastases,\r\n             defined as untreated and symptomatic or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms.\r\n\r\n          -  Has multiple primary malignancies within 3 years, except adequately resected\r\n             non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors\r\n             curatively treated.\r\n\r\n          -  History of severe hypersensitivity reactions to either the T-DXd or inactive\r\n             ingredients in T-DXd.\r\n\r\n          -  History of severe hypersensitivity reactions to other monoclonal antibodies or any\r\n             components used in the ramucirumab drug product preparation\r\n\r\n          -  Known allergy or hypersensitivity to paclitaxel or any components used in the\r\n             paclitaxel preparation or other contraindication for taxane therapy such as peripheral\r\n             neuropathy, Grade 2.\r\n\r\n          -  Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an\r\n             unexplained fever >38.0C during Screening visits or on the first scheduled day of\r\n             dosing (at the discretion of the Investigator, participants with tumor fever may be\r\n             enrolled), which in the Investigator's opinion might compromise the participant's\r\n             participation in the study or affect the study outcome\r\n\r\n          -  Clinically significant gastrointestinal disorder (eg, including hepatic disorders,\r\n             bleeding, inflammation, occlusion, ileus, diarrhea Grade >1, jaundice, intestinal\r\n             paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or\r\n             partial bowel obstruction) in the opinion of Investigator\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Gastric Cancer, Adenocarcinoma|Gastroesophageal Junction Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab deruxtecan","description":"6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle"},{"intervention_type":"Drug","name":"Drug: Ramucirumab","description":"8 mg/kg IV infusion on Days 1 and 15 of a 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"80 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel","time_frame":"Time from date of randomization until death (due to any cause), up to approximately 36 months","description":"Overall survival (OS) is defined as the time from date of randomization until death from any cause."},{"outcome_type":"secondary","measure":"Progression-free Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel","time_frame":"Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months","description":"Progression-free survival (PFS) is defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment."},{"outcome_type":"secondary","measure":"Objective Response Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel","time_frame":"From start of treatment to date of documented disease progression, up to approximately 36 months","description":"Objective response rate (ORR) is defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator."},{"outcome_type":"secondary","measure":"Duration of Response in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel","time_frame":"Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months","description":"Duration of response (DoR) is defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment."},{"outcome_type":"secondary","measure":"Disease Control Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel","time_frame":"From start of treatment to date of documented disease progression, up to approximately 36 months","description":"Disease control rate (DCR) is defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment."},{"outcome_type":"secondary","measure":"Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and Physical Examination Findings","time_frame":"From time subjects signs informed consent form up to 40 days after last study dose","description":"Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0."},{"outcome_type":"secondary","measure":"Serum Concentrations for Trastuzumab Deruxtecan, total anti-HER2 antibody, and Active Metabolite MAAA-1181a","time_frame":"Cycles 1-4 and subsequent cycles on Day 1 pre- and post-infusion (each cycle is 28 days)"},{"outcome_type":"secondary","measure":"Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)","time_frame":"Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, end of treatment, 40 day follow up, and long-term follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)","description":"The immunogenicity of trastuzumab deruxtecan will be assessed."},{"outcome_type":"secondary","measure":"Percentage of Participants Who Have Treatment-emergent ADAs","time_frame":"Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, end of treatment, 40 day follow up, and long-term follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)","description":"The immunogenicity of trastuzumab deruxtecan will be assessed."}]}
{"nct_id":"NCT04857138","start_date":"2021-05-18","phase":"Phase 1","enrollment":280,"brief_title":"A Study to Evaluate Safety, Pharmacokinetics and Anti-Tumor Activity of RO7300490, as Single Agent or in Combination With Atezolizumab in Participants With Advanced Solid Tumors","official_title":"An Open-Label, Multicenter, Dose-Escalation and Expansion, Phase I Study to Evaluate Safety, Pharmacokinetics, And Anti-Tumor Activity of RO7300490, A Fibroblast Activation Protein- (FAP) Targeted CD40 Agonist, as Single Agent or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors","primary_completion_date":"2026-08-17","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-08-17","last_update":"2021-09-22","description":"A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: [Part 1] Dose-Escalation of RO7300490 as a single agent; [Part 2] Dose-Escalation of RO7300490 in combination with atezolizumab and [Part 3] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.","other_id":"WP42627","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Life expectancy of >= 12 weeks.\r\n\r\n          -  Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors\r\n             that are not amenable to standard therapy.\r\n\r\n          -  Radiologically measurable disease as defined by Response Evaluation Criteria in Solid\r\n             Tumors (RECIST) v1.1.\r\n\r\n          -  Agreement to provide protocol-specific biopsy material.\r\n\r\n          -  Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<1.\r\n\r\n          -  Adequate performance status and cardiovascular, hematological, liver, renal and\r\n             coagulation function.\r\n\r\n          -  For female participants of childbearing potential: agreement to remain abstinent\r\n             (refrain from heterosexual intercourse), use contraceptive measures and refrain from\r\n             donating eggs.\r\n\r\n          -  For male participants: agreement to remain abstinent (refrain from heterosexual\r\n             intercourse), use contraceptive measures and refrain from donating sperm.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known central nervous system (CNS) primary tumors or metastases, including\r\n             leptomeningeal metastases.\r\n\r\n          -  Active second malignancy requiring anticancer treatment and/or palliative supportive\r\n             care.\r\n\r\n          -  Significant cardiovascular/cerebrovascular disease within 6 months prior to study\r\n             treatment start.\r\n\r\n          -  Any other diseases, metabolic dysfunction, physical examination finding or clinical\r\n             laboratory finding that gives reasonable suspicion of a disease or condition that\r\n             would contraindicate the use of an investigational drug.\r\n\r\n          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation.\r\n\r\n          -  Active or history of autoimmune disease.\r\n\r\n          -  Known hypersensitivity to any of the components of RO7300490 formulation or to\r\n             components of atezolizumab formulation.\r\n\r\n          -  Pregnancy, lactation or breastfeeding.\r\n\r\n          -  Dementia or altered mental status that would prohibit informed consent.\r\n\r\n          -  Major surgery or significant traumatic injury within 28 days prior to the first study\r\n             drug administration (excluding biopsies) or anticipation of the need for major surgery\r\n             during study treatment.\r\n\r\n          -  Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy,\r\n             immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of\r\n             the drug (whichever is shorter) before the first study drug administration.\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: RO7300490","description":"Participants will receive RO7300490, as described in the Arm Descriptions."},{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Participants will receive Atezolizumab, as described in the Arm Descriptions."}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2)","time_frame":"Up to 36 months"},{"outcome_type":"primary","measure":"Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2)","time_frame":"Up to 36 months"},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) (Part 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Clearance (CL) of RO7300490 (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) (Parts 1 and 2)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3)","time_frame":"Up to 48 months"},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events (AEs) (Part 3)","time_frame":"Up to 48 months"}]}
{"nct_id":"NCT04862195","start_date":"2021-05-15","phase":"N/A","enrollment":553,"brief_title":"Registrational Trial to Compare Effectiveness of Two Digital Software Medical Devices as Adjunctive Oncology Treatment","official_title":"Double-blinded, Randomized, Adaptive Registrational Trial to Compare Effectiveness of Two Digital Software Medical Devices (Attune and Cerena) as Interventions for Physical and Emotional Health in Adjunctive Oncology Treatment","primary_completion_date":"2022-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-08-31","last_update":"2021-09-05","description":"This is a non-significant risk, double-blinded, randomized, registrational study to compare the effectiveness of two digital, software only, medical devices (SaMD) (attune and cerena) in reducing cancer-related anxiety and depression symptoms when used adjunctively with multidisciplinary (medical, psychosocial) oncology usual care regimens for up to 10 weeks. Study population will consist of up to 553 participants with stage I-III breast cancer or stage I-III NSCLC. The primary endpoint is percent improvement in anxiety symptoms at Week 10 and secondary endpoints of percent improvement in depressive symptoms will be assessed at Week 12. An interim analysis for efficacy and futility will be conducted once 236 participants have completed the study.","other_id":"PROT001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Stage I-III breast cancer or Stage I-III NSCLC who are currently in active treatment\r\n             or have completed initial cancer directed treatments (surgery, radiation,\r\n             chemotherapy) within the past 3 months;\r\n\r\n          -  Are experiencing at least moderate anxiety (GAD-7 >10) or mild-to-moderate depression\r\n             (PHQ-8 score 5-11);\r\n\r\n          -  Are fluent in English; and\r\n\r\n          -  Have access to smartphone, or tablet capable of running iOS or Android software.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previous history of cancer;\r\n\r\n          -  <2-yr survival prognosis as determined by treating clinician;\r\n\r\n          -  Currently participating in investigative CBT trial for treatment of anxiety or\r\n             depression;\r\n\r\n          -  Participant is unable to complete training, has cognitive deficits, more severe\r\n             psychiatric conditions, lack of access to internet accessible device or psycho-social\r\n             conditions (e.g., other social conditions, that would interfere with adherence to\r\n             self-directed care), such that in investigator's opinion the participant would be\r\n             unable to complete the study;\r\n\r\n          -  Recently completed use of Blue Note Therapeutics Covid Cancer Care Program or other\r\n             Blue Note Therapeutics-sponsored study; and\r\n\r\n          -  PHQ-9 Q9 response >0 AND Columbia Suicide Severity Risk Scale (or equivalent) score of\r\n             Category 2- \"suicidal ideation\" at screening.\r\n      ","sponsor":"Blue Note Therapeutics","sponsor_type":"Industry","conditions":"Anatomic Stage I Breast Cancer AJCC v8|Anatomic Stage II Breast Cancer AJCC v8|Anatomic Stage III Breast Cancer AJCC v8|Stage I Lung Cancer AJCC v8|Stage II Lung Cancer AJCC v8|Stage III Lung Cancer AJCC v8","interventions":[{"intervention_type":"Device","name":"Device: Attune","description":"Software as a medical device"},{"intervention_type":"Device","name":"Device: Cerena","description":"Software as a medical device"}],"outcomes":[{"outcome_type":"primary","measure":"Cancer-related symptoms of anxiety (1)","time_frame":"Baseline up to Week 10","description":"Percent reduction in PROMIS-A scores, reduction indicates reduced anxiety"},{"outcome_type":"secondary","measure":"Cancer-related symptoms of depression (1)","time_frame":"Baseline up to Week 10","description":"Percent reduction in PROMIS-D scores, reduction indicates reduced depression"},{"outcome_type":"secondary","measure":"Cancer-related symptoms of anxiety (2)","time_frame":"Baseline up to Week 12","description":"Percent reduction in PROMIS-A scores, reduction indicates reduced anxiety"},{"outcome_type":"secondary","measure":"Cancer-related symptoms of anxiety (3)","time_frame":"Baseline up to Week 10","description":"Percent reduction in Clinical Global Impression Scale and Improvement scores, reduction indicates reduced anxiety"},{"outcome_type":"secondary","measure":"Cancer-related symptoms of depression (4)","time_frame":"Baseline up to Week 12","description":"Percent reduction in Clinical Global Impression Scale and Improvement scores, reduction indicates reduced depression"},{"outcome_type":"secondary","measure":"Mean mHealth App Usability Questionnaire (MAUQ) for Standalone mHealth Apps Used by Patients","time_frame":"Baseline up to Week 10","description":"Higher scores indicate higher ease of use / easier to use applications"},{"outcome_type":"other","measure":"Quality of life via PROMIS-Global Health v1.2","time_frame":"Weeks 10 and Week 12","description":"The PROMIS Global Health measures assess an individual's physical, mental, and social health. The measures are generic, rather than disease-specific, and often use an \"In General\" item context as it is intended to globally reflect individuals' assessment of their health. The adult PROMIS Global Health measure produces two scores: Physical Health and Mental Health (Promis-Global Health Scoring Manual, 2017). Higher scores for responses always indicate better health."},{"outcome_type":"other","measure":"Patient self-efficacy via the Patient Activation Measure-13 (PAM-13)","time_frame":"Weeks 10","description":"Patient Activation Measures-the knowledge, skills, and confidence to manage one's health is associated with improved self-management behaviors in cancer patients. A patient activation measure (PAM) using PAM-13 will be used to assess participant engagement at baseline after PROMIS-A and PROMIS-D are completed and at Week 10. Higher scores indicate higher self-efficacy."},{"outcome_type":"other","measure":"Patient self-efficacy via the Measurement of Current Status (MOCS) Part A and Part B","time_frame":"Baseline, Week 6, and Week 10","description":"The Measure of Current Status (MOCS) scale comes from research on the effects of a multi-modal cognitive-behavioral stress management intervention on the psychosocial well-being of cancer patients. The MOCS has two sections. Part A is items measuring participants' current self-perceived status on several skills that are targeted by the intervention: the ability to relax at will, recognize stress-inducing situations, restructure maladaptive thoughts, be assertive about needs, and choose appropriate coping responses as needed. Part B assesses potential \"nonspecific effects\" of the intervention: feelings of normalcy vs. alienation, sense of cohesiveness with other patients, perceptions of care from persons around them, and a sense of being better off than other cancer patients. All items were framed in such a way that they are sensible to participants in both conditions. MOCS measurements will be taken at Baseline, Week 6, and Week 10. Higher scores indicate higher self-efficacy."},{"outcome_type":"other","measure":"Immune cell transcription","time_frame":"Baseline up to Week 12","description":"Analyses will focus on inflammatory gene expression and related gene regulation pathways due to their established relevance for disease progression/recurrence in the aftermath of cancer diagnosis and treatment, and their role in promoting symptoms of depression or anxiety via effects on central nervous system function"}]}
{"nct_id":"NCT04900363","start_date":"2021-05-14","phase":"Phase 1/Phase 2","enrollment":360,"brief_title":"A Trial of AK112 (PD-1/VEGF Bispecific Antibody) in Patients With NSCLC","official_title":"A Phase Ib/II Trial of AK112 (PD-1/VEGF Bispecific Antibody) in Patients With Advanced NSCLC","primary_completion_date":"2023-05-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-05-31","last_update":"2021-05-25","description":"This trial is a Phase Ib/II study. All patients are stage IIIB/C or IV non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 in subjects with advanced NSCLC whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.","other_id":"AK112-202","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically or cytologically confirmed diagnosis of NSCLC.\r\n\r\n          -  Has StageIIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC]).\r\n\r\n          -  18 to 75 years old (at the time consent is obtained).\r\n\r\n          -  Be able and willing to provide written informed consent and to comply with all\r\n             requirements of study participation (including all study procedures).\r\n\r\n          -  Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from\r\n             either a core or excisional tumor biopsy.\r\n\r\n          -  Has a life expectancy of at least 3 months.\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          -  Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\r\n             1.1 as determined by the site study team.\r\n\r\n          -  Has adequate organ function.\r\n\r\n          -  Has recovered from the effects of any prior radiotherapy or surgery.\r\n\r\n          -  All female and male subjects of reproductive potential must agree to use an effective\r\n             method of contraception, as determined by the Investigator, during and for 120 days\r\n             after the last dose of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Is currently participating in a study of an investigational agent or using an\r\n             investigational device.\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2\r\n             years prior to the first dose of study treatment.\r\n\r\n          -  Has undergone major surgery within 30 days of Study Day 1.\r\n\r\n          -  Has a known additional malignancy that is progressing or requires systemic treatment.\r\n             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the\r\n             skin that has undergone potentially curative therapy or in situ cervical cancer.\r\n\r\n          -  Has known active central nervous system (CNS) metastases.\r\n\r\n          -  Has carcinomatous meningitis.\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in the past 2\r\n             years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive\r\n             drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid\r\n             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a\r\n             form of systemic treatment.\r\n\r\n          -  Has an active infection requiring systemic therapy.\r\n\r\n          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA\r\n             [qualitative] is detected).\r\n\r\n          -  History of myocardial infarction, unstable angina, congestive heart failure within 12\r\n             months prior to day 1 of study treatment.\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the study, interfere with the subject's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             this subject to participate, in the opinion of the treating investigator.\r\n\r\n          -  Has known psychiatric or substance abuse disorders that would interfere with\r\n             cooperation with the requirements of the study.\r\n\r\n          -  Has received a live virus vaccine within 30 days of the planned first dose of study\r\n             therapy.\r\n\r\n          -  Is pregnant, breastfeeding, or expecting to conceive or father a child within the\r\n             projected duration of the study including 120 days following the last dose of study\r\n             treatment.\r\n\r\n          -  Has any concurrent medical condition that, in the opinion of the Investigator, would\r\n             complicate or compromise compliance with the study or the well-being of the subject.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AK112","description":"Subjects receive AK112 intravenously."}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rates (ORR)","time_frame":"Up to approximately 2 years","description":"ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1."},{"outcome_type":"primary","measure":"Number of participants with adverse events (AEs)","time_frame":"Up to approximately 2 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment."},{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"Up to approximately 2 years","description":"PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"up to 2 years","description":"Disease control rate (DCR) assessed according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"up to 2 years","description":"Duration of response (DOR) assessed according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"up to 2 years","description":"Overall survival is defined as the time from the start of treatment with AK112 until death due to any cause."},{"outcome_type":"secondary","measure":"Maximum observed concentration (Cmax) of AK112","time_frame":"Up to 2 years","description":"Serum concentrations of AK112 in individual subjects at different time points after AK112 administration"},{"outcome_type":"secondary","measure":"Anti-drug antibodies (ADA)","time_frame":"Up to 2 years","description":"Number of subjects with detectable anti-drug antibodies (ADA)"},{"outcome_type":"secondary","measure":"PD-L1 expression","time_frame":"Up to 2 years","description":"The correlationship between PD-L1 expression and AK112 anti-tumor activity"}]}
{"nct_id":"NCT04752215","start_date":"2021-05-12","phase":"Phase 1","enrollment":120,"brief_title":"A Study Evaluating Different Doses of BI 765049 When Given Alone and When Given With BI 754091 to Patients With Advanced Solid Tumors Having the B7-H6 Marker","official_title":"A First-in-human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 765049 and BI 765049 + BI 754091 Administered by Repeated Intravenous Infusions in Patients With Malignant Solid Tumors Expressing B7-H6","primary_completion_date":"2023-02-13","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-15","last_update":"2021-09-08","description":"This study is open to adults with advanced solid tumors whose previous cancer treatment was not successful. People can participate if their tumor has the B7-H6 marker or if they have colorectal cancer. The study tests 2 medicines called BI 765049 and BI 754091. Both medicines may help the immune system fight cancer. The purpose of this study is to find out the highest dose of BI 765049 alone and in combination with BI 754091 the participants can tolerate. In this study, BI 765049 is given to people for the first time. Participants can stay in the study for up to 3 years, if they benefit from treatment and can tolerate it. During this time, they get BI 765049 alone or in combination with BI 754091 as infusion into a vein every 3 weeks. The doctors check the health of the participants and note any health problems that could have been caused by BI 765049 or BI 754091. The doctors also regularly monitor the size of the tumor.","other_id":"1454-0001","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Signed and dated, written informed consent form (ICF) (ICF1 for B7-H6 testing for all\r\n             patients except those with advanced or metastatic colorectal cancer (CRC); and ICF2\r\n             for all patients) describing the study in accordance with International Council on\r\n             Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to any\r\n             trial-specific procedures, sampling, or analyses.\r\n\r\n          -  Patient must be 18 years of age at the time of signature on the ICFs (ICF1 and ICF2).\r\n\r\n          -  Patients with a histologically or cytologically confirmed diagnosis of an advanced,\r\n             unresectable, and/or metastatic colorectal carcinoma (CRC), non-small cell lung cancer\r\n             (NSCLC), hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma\r\n             (HNSCC), gastric carcinoma, and pancreatic carcinoma. At least 1 patient in each\r\n             back-fill slot must be a non-CRC patient (i.e., NSCLC, HCC, HNSCC, gastric carcinoma,\r\n             or pancreatic carcinoma).\r\n\r\n          -  Patients with disease progression despite conventional treatment, intolerant to or not\r\n             a candidate for conventional treatment, or with a tumor for which no conventional\r\n             treatment exists.\r\n\r\n          -  All patients must agree to the collection of tumor samples (as slides from archival\r\n             diagnostic samples or fresh tumor biopsies) for confirmation of B7-H6 expression\r\n             either at Screening visit 02 (for CRC patients) or Screening visit 01 (for all other\r\n             patients). To qualify for a back-fill slot or recommended dose expansion (RDE) cohort,\r\n             the patient must agree to the collection of mandatory pre-treatment and on-treatment\r\n             fresh tumor biopsies.\r\n\r\n          -  Patient diagnosed with advanced or metastatic CRC or patient with confirmed B7-H6\r\n             expression on tumor tissue sample (archived or fresh tumor biopsy) based on central\r\n             pathology review.\r\n\r\n          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or\r\n             1.\r\n\r\n          -  Patient must have at least one evaluable target lesion outside of the central nervous\r\n             system (CNS) as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\r\n             separate from any lesion(s) identified for tumor biopsy.\r\n\r\n          -  Further inclusion criteria apply\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Patient with a history of a major surgery within 28 days prior to first dose of BI\r\n             765049 (major according to the Investigator's and/or Medical Monitor's assessment).\r\n\r\n          -  Patient with a history of a previous or concomitant malignancies. Patient with a\r\n             malignancy considered effectively treated and cured by 'local treatment' within the\r\n             last 2 years and that is distinct from the one treated in this trial will be allowed.\r\n\r\n          -  Patient with known leptomeningeal disease or spinal cord compression due to disease.\r\n\r\n          -  Patient requiring anticoagulant treatment which cannot be safely interrupted, if\r\n             medically needed for a study procedure (e.g., biopsy) based on the opinion of the\r\n             Investigator.\r\n\r\n          -  History of systemic antimicrobials required for an infection within 7 days of first\r\n             dose BI 765049.\r\n\r\n          -  Patient with any of the following laboratory evidence of hepatitis virus infection.\r\n             Test results obtained in routine diagnostics are acceptable for screening if done\r\n             within 14 days before the ICF2 date:\r\n\r\n               -  Positive results of hepatitis B surface (HBs) antigen\r\n\r\n               -  Presence of hepatitis B core (HBc) antibody together with hepatitis B virus\r\n                  (HBV)-DNA\r\n\r\n               -  Presence of hepatitis C-RNA\r\n\r\n          -  Patient with known human immunodeficiency virus (HIV) infection.\r\n\r\n          -  Patient previous treatment history:\r\n\r\n               -  Treatment with a systemic anti-cancer therapy or investigational drug within 21\r\n                  days or 5 half-lives (whichever is shorter) of the first administration of BI\r\n                  765049.\r\n\r\n               -  Treatment with extensive field radiotherapy including whole brain irradiation\r\n                  within 2 weeks prior to first administration of BI 765049.\r\n\r\n          -  Further exclusion criteria apply\r\n      ","sponsor":"Boehringer Ingelheim","sponsor_type":"Industry","conditions":"Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms, Carcinoma, Hepatocellular, Head and Neck Neoplasms, Gastrointestinal Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: BI 765049","description":"BI 765049"},{"intervention_type":"Drug","name":"Drug: BI 754091","description":"BI 754091"}],"outcomes":[{"outcome_type":"primary","measure":"Maximum tolerated dose (MTD) in any studied regimen","time_frame":"Up to 3 weeks","description":"defined as the highest dose with less than 25 percent (%) risk of the true dose limiting toxicity (DLT) rate being equal to or above 33 percent (%) during the MTD evaluation period"},{"outcome_type":"primary","measure":"Number of patients with dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period","time_frame":"Up to 3 weeks"},{"outcome_type":"secondary","measure":"Maximum measured concentration of BI 765049 (Cmax)","time_frame":"Up to 36 months"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ)","time_frame":"Up to 36 months"},{"outcome_type":"secondary","measure":"Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients with measurable disease","time_frame":"Up to 36 months"}]}
{"nct_id":"NCT04862663","start_date":"2021-05-10","phase":"Phase 3","enrollment":700,"brief_title":"Capivasertib + Palbociclib + Fulvestrant for HR+/HER2- Advanced Breast Cancer (CAPItello-292).","official_title":"A Phase Ib/III Randomised Study of Capivasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer","primary_completion_date":"2024-10-21","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-01-15","last_update":"2021-09-02","description":"A Phase Ib/III Randomised Study of Capivasertib plus Palbociclib and Fulvestrant versus Placebo plus Palbociclib and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292).","other_id":"D361DC00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","intervention_model_description":"Phase Ib: Open, Parallel groups allowed, recruiting approx. 72 participants. Phase III: Randomised, double blind, recruiting approx. 628 participants.","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":99,"population":"","criteria":"\n        Key inclusion criteria for both phases:\r\n\r\n          1. Adult females (pre- and/or post-menopausal), and adult males.\r\n\r\n          2. Histologically confirmed HR+/ HER2- breast cancer determined from the most recent\r\n             tumour sample (primary or metastatic) per the American Society of Clinical Oncology\r\n             and College of American Pathologists guideline. To fulfil the requirement of HR+\r\n             disease, a breast cancer must express ER with or without co-expression of progesterone\r\n             receptor.\r\n\r\n          3. Eligible for palbociclib and fulvestrant therapy as per investigator assessment.\r\n\r\n          4. Adequate organ and bone marrow functions.\r\n\r\n          5. Consent to provide a mandatory FFPE tumour sample.\r\n\r\n        Inclusion criteria only for phase III:\r\n\r\n          1. Radiologic measurable relapse during neoadjuvant / adjuvant endocrine therapy or\r\n             evidence of relapse within 12 months of completion of adjuvant therapy or disease\r\n             progression during the initial 12 months of 1L endocrine therapy in locally advanced\r\n             unresectable or metastatic breast cancer.\r\n\r\n          2. Received up to a maximum of 1 lines of prior chemotherapy in the advanced setting.\r\n\r\n        Key exclusion criteria for both phases:\r\n\r\n          1. History of another primary malignancy except for malignancy treated with curative\r\n             intent with no known active disease  5 years before the first dose of study\r\n             intervention and of low potential risk for recurrence.\r\n\r\n          2. Radiotherapy with a wide field of radiation within 4 weeks prior to study treatment\r\n             initiation and/or radiotherapy with a limited field of radiation for palliation within\r\n             2 weeks prior to study treatment initiation. Patients who received prior radiotherapy\r\n             to 25% of bone marrow are not eligible independent of when it was received.\r\n\r\n          3. Major surgery (excluding placement of vascular access) within 4 weeks of the first\r\n             dose of study treatment.\r\n\r\n          4. Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy,\r\n             excluding alopecia. Participants with irreversible toxicity that is not reasonably\r\n             expected to be exacerbated by study intervention may be included (eg, hearing loss)\r\n             after consultation with the AstraZeneca study physician.\r\n\r\n          5. Spinal cord compression, brain metastases or leptomeningeal metastases unless\r\n             asymptomatic, treated and stable and not requiring steroids within 4 weeks prior to\r\n             study treatment initiation.\r\n\r\n          6. Any of the following cardiac criteria at screening:\r\n\r\n               1. . Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive\r\n                  ECGs\r\n\r\n               2. . Any clinically important abnormalities in rhythm, conduction or morphology of\r\n                  resting ECG (eg, complete left bundle branch block, third-degree heart block)\r\n\r\n               3. . Any factors that increase the risk of QTc prolongation or risk of arrhythmic\r\n                  events\r\n\r\n               4. . Experience of any of the following procedures or conditions in the preceding 6\r\n                  months: coronary artery bypass graft, angioplasty, vascular stent, myocardial\r\n                  infarction, angina pectoris, congestive heart failure New York Heart Association\r\n                  (NYHA) grade  2\r\n\r\n               5. . Uncontrolled hypotension\r\n\r\n               6. . Cardiac ejection fraction outside institutional range of normal or < 50%\r\n                  (whichever is higher)\r\n\r\n          7. Any of these clinically significant abnormalities of glucose metabolism at screening:\r\n\r\n               1. . diabetes mellitus type I or type II requiring insulin treatment\r\n\r\n               2. . HbA1c  8.0% (63.9 mmol/mol)\r\n\r\n          8. Previous allogeneic bone marrow transplant or solid organ transplant.\r\n\r\n        Key exclusion criteria for the phase III only:\r\n\r\n        1. Prior treatment with CDK4/6 inhibitors (any setting), a SERD (including unlicensed\r\n        SERDs), allosteric mTOR inhibitors (e.g. everolimus), PI3K inhibitors (e.g. alpelisib) or\r\n        AKT inhibitors.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Locally Advanced (Inoperable) or Metastatic Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Capivasertib","description":"Phase Ib: potential range 200 mg, 320 mg, 400 mg, all BD. Days 1 to 4 in each week of a 28-day treatment cycle Phase III: 400 mg (BD 4 days on 3 days off/week for 4 weeks), depending on tolerability observed in Phase Ib"},{"intervention_type":"Drug","name":"Drug: Capivasertib Placebo","description":"Phase Ib: Not applicable Phase III: 400 mg (BD 4 days on 3 days off/week for 4 weeks), depending on tolerability observed in Phase Ib"},{"intervention_type":"Drug","name":"Drug: Fulvestrant","description":"Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter"},{"intervention_type":"Drug","name":"Drug: Palbociclib","description":"Phase Ib: potential range 75 mg, 100 mg, 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: 125 mg (OD 21 days of 28- day cycle), depending on tolerability observed in Phase Ib"}],"outcomes":[{"outcome_type":"primary","measure":"Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol.","time_frame":"Within the first 28 day cycle.","description":"Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria."},{"outcome_type":"primary","measure":"Phase Ib: 2. The number of participants with treatment-related adverse events.","time_frame":"From baseline up to approximately 24 months.","description":"Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events."},{"outcome_type":"primary","measure":"Phase Ib: 3. The number of participants with treatment-related serious adverse events.","time_frame":"From baseline up to approximately 24 months.","description":"Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events."},{"outcome_type":"primary","measure":"Phase III: 1. Progression Free Survival (PFS).","time_frame":"Up to approximately 33 months.","description":"Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by the investigator or death due to any cause."},{"outcome_type":"secondary","measure":"Phase Ib: 1. PK parameters for palbociclib: Cmax.","time_frame":"Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).","description":"Maximum observed plasma (peak) drug concentration."},{"outcome_type":"secondary","measure":"Phase Ib: 2. PK parameters for palbociclib: AUC0-72h.","time_frame":"Cycle 0 (Cycle 0 is 3 days).","description":"Partial area under the plasma concentration-time curve from zero to 72 hours post-dose."},{"outcome_type":"secondary","measure":"Phase Ib: 3. PK parameters for palbociclib: AUC0-24h.","time_frame":"Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).","description":"Partial area under the plasma concentration-time curve from zero to 24 hours post-dose."},{"outcome_type":"secondary","measure":"Phase Ib: 4. PK parameters for palbociclib: Cmin.","time_frame":"Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days).","description":"Minimum observed plasma drug concentration."},{"outcome_type":"secondary","measure":"Phase Ib: 5. PK parameters for capivasertib: Cmax.","time_frame":"Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).","description":"Maximum observed plasma (peak) drug concentration."},{"outcome_type":"secondary","measure":"Phase Ib: 6. PK parameters for capivasertib: AUC0-12h.","time_frame":"Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).","description":"Partial area under the plasma concentration-time curve from zero to 12 hours post-dose."},{"outcome_type":"secondary","measure":"Phase Ib: 7. PK parameters for capivasertib: Cmin.","time_frame":"Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).","description":"Minimum observed plasma drug concentration."},{"outcome_type":"secondary","measure":"Phase Ib: 8. Objective Response Rate (ORR).","time_frame":"Up to approximately 24 months.","description":"Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)."},{"outcome_type":"secondary","measure":"Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks.","time_frame":"Up to approximately 24 months.","description":"Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose."},{"outcome_type":"secondary","measure":"Phase Ib: 10. Duration of Response (DoR).","time_frame":"Up to approximately 24 months.","description":"Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause."},{"outcome_type":"secondary","measure":"Phase Ib: 11. Progression Free Survival (PFS).","time_frame":"Up to approximately 24 months.","description":"Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause."},{"outcome_type":"secondary","measure":"Phase III: 1. Overall Survival (OS).","time_frame":"Up to approximately 60 months.","description":"Overall Survival (OS) - time from randomisation until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Phase III: 2. Progression Free Survival (PFS) in PIK3CA/ AKT1/ PTEN-altered population.","time_frame":"Up to approximately 33 months.","description":"Progression Free Survival (PFS) - time from randomisation until progression per RECIST v 1.1 as assessed by the PI or death due to any cause."},{"outcome_type":"secondary","measure":"Phase III: 3. Progression Free Survival 2 (PFS2).","time_frame":"Up to approximately 60 months.","description":"Progression Free Survival (PFS2) - time from randomisation to the earliest of the progression event, subsequent to first therapy or death."},{"outcome_type":"secondary","measure":"Phase III: 4. Objective Response Rate (ORR).","time_frame":"Up to approximately 33 months.","description":"Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response."},{"outcome_type":"secondary","measure":"Phase III: 5. Duration of Response (DoR).","time_frame":"Up to approximately 33 months.","description":"Duration of Response (DoR) - the time from the date of first documented response until the date of progression or death."},{"outcome_type":"secondary","measure":"Phase III: 6. Clinical Benefit Rate (CBR) at 24 weeks.","time_frame":"Up to approximately 33 months.","description":"Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD for at least 23 weeks after randomization."},{"outcome_type":"secondary","measure":"Phase III: 7. EORTC QLQ-30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items).","time_frame":"Up to approximately 60 months.","description":"5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity."},{"outcome_type":"secondary","measure":"Phase III: 8. 1.EORTC QLQ BR45 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module).","time_frame":"Up to approximately 60 months.","description":"The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional items yield two multi-item scales: a target symptom scale with three subscales (endocrine therapy, endocrine sexual and skin/mucosa) and a satisfaction scale. In addition, 3 single items are included that assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: \"Not at All,\" \"A Little,\" \"Quite a Bit,\" and \"Very Much\". Scores are transformed to a 0 to 100 scale, where higher scores indicate better functioning, better HRQoL, or greater level of symptoms."},{"outcome_type":"secondary","measure":"Phase III: 9. Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status.","time_frame":"Up to approximately 60 months.","description":"Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline."},{"outcome_type":"secondary","measure":"Phase III: 10. Plasma concentration of capivasertib pre- and post-dose.","time_frame":"Up to approximately 60 months.","description":"Plasma concentration of capivasertib pre-, and post-dose."},{"outcome_type":"secondary","measure":"Phase III: 11. The number of participants with adverse events.","time_frame":"Up to approximately 60 months.","description":"Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events."},{"outcome_type":"secondary","measure":"Phase III: 12. The number of participants with serious adverse events.","time_frame":"Up to approximately 60 months.","description":"Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events."}]}
{"nct_id":"NCT04675333","start_date":"2021-05-10","phase":"Phase 2","enrollment":112,"brief_title":"Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04)","official_title":"A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04)","primary_completion_date":"2023-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-10-31","last_update":"2021-08-20","description":"A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma.","other_id":"AT148004","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Previously untreated metastatic or unresectable, recurrent head and neck squamous cell\r\n             carcinoma.\r\n\r\n          -  Adequate Bone Marrow Function.\r\n\r\n          -  Adequate Renal & Liver Function.\r\n\r\n          -  Adequate Performance Status\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Patients with known symptomatic CNS metastases or leptomeningeal disease requiring\r\n             steroids.\r\n\r\n          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.\r\n\r\n          -  Prior treatment with any anti-CD47 or anti-SIRP agent.\r\n\r\n          -  Prior treatment with anti-PD-1 or PD-L1.\r\n      ","sponsor":"ALX Oncology Inc.","sponsor_type":"Industry","conditions":"Head and Neck Cancer|Head and Neck Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Evorpacept","description":"IV Q3W"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"IV Q3W"},{"intervention_type":"Drug","name":"Drug: Cisplatin/Carboplatin; 5FU","description":"IV Q3W"}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate per RECIST 1.1","time_frame":"Last randomized patient reaching at least 24 weeks of follow-up."}]}
{"nct_id":"NCT04660812","start_date":"2021-05-10","phase":"Phase 1/Phase 2","enrollment":250,"brief_title":"An Open Label Study Evaluating the Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer.","official_title":"A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating The Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer","primary_completion_date":"2023-09-20","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-18","last_update":"2021-08-30","description":"This randomized phase 1b/2 open-label study will evaluate the efficacy of etrumadenant (AB928) treatment combinations in patients with metastatic colorectal cancer.","other_id":"ARC-9","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Single","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Male and female participants  18 years of age\r\n\r\n          -  Histologically confirmed metastatic colorectal adenocarcinoma\r\n\r\n          -  Must have at least 1 measurable lesion per RECIST v1.1\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  Life expectancy at least 3 months\r\n\r\n          -  Adequate hematologic and end-organ function\r\n\r\n          -  Negative HIV, Hep B and Hep C antibody testing\r\n\r\n          -  Agreement to remain abstinent or use contraceptive measures with female partners of\r\n             reproductive potential, and agreement to refrain from donating sperm, for 30 days\r\n             after the last dose of etrumadenant, 90 days after the last dose of zim, 180 days\r\n             after mFOLFOX-6 and 180 days after bev, whichever is longer.\r\n\r\n               -  Inclusion Criteria for Cohort A:\r\n\r\n          -  Disease progression following not more than one prior line of treatment for mCRC that\r\n             consisted of oxaliplatin or irinotecan containing chemotherapy in combination with a\r\n             biologic agent\r\n\r\n               -  Inclusion Criteria for Cohort B:\r\n\r\n          -  Disease progression during or following not more that two separate lines of treatment\r\n             for mCRC that consisted of oxaliplatin, and irinotecan containing chemotherapy in\r\n             combination with a biologic agent\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previous anticancer treatment within 4 weeks prior to initiation of study treatment\r\n\r\n          -  Prior allogeneic stem cell or solid organ transplant\r\n\r\n          -  Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of\r\n             study treatment\r\n\r\n          -  Use of any live vaccines against infectious diseases within 28 days of first dose.\r\n\r\n          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)\r\n             metastases\r\n\r\n          -  Current treatment with anti-viral therapy for HBV\r\n\r\n          -  Structurally unstable bone lesions suggesting impending fracture\r\n\r\n          -  History or leptomeningeal disease\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced\r\n             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening\r\n             chest CT scan\r\n\r\n          -  History of malignancy other than colorectal cancer within 2 years prior to screening,\r\n             except for malignancies such as non-melanoma skin carcinoma or ductal carcinoma in\r\n             situ\r\n\r\n          -  Active tuberculosis\r\n\r\n          -  Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior\r\n             to initiating study treatment\r\n\r\n          -  Severe infection within 4 weeks (28 days) prior to initiation of study treatment\r\n\r\n          -  Significant cardiovascular disease, unstable or new onset of angina within 3 months\r\n             prior to initiation of treatment, or myocardial infarction within 6 months prior to\r\n             study treatment or unstable arrhythmia\r\n\r\n          -  Major surgical procedures, other than for diagnosis, within 4 weeks prior to\r\n             initiation of study treatment, or anticipation of need for major surgical procedure\r\n             during the study\r\n\r\n          -  Known allergy or hypersensitivity to any of the study drugs or their excipients\r\n\r\n          -  Inability to swallow medications\r\n\r\n          -  Malabsorption condition that would alter the absorption of orally administered\r\n             medications\r\n\r\n          -  Evidence of inherited bleeding diathesis or significant coagulopathy at risk of\r\n             bleeding (i.e., in the absence of therapeutic anticoagulation)\r\n\r\n          -  Prior treatment with an agent targeting the adenosine pathway\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency, including, but not\r\n             limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus\r\n             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid\r\n             antibody syndrome, Wegener granulomatosis, Sjgren syndrome, Guillain Barr syndrome,\r\n             or multiple sclerosis\r\n\r\n               -  Exclusion Criteria for Cohorts A and B:\r\n\r\n          -  Prior treatment with immune checkpoint blockade therapies including anit-cytotoxic T\r\n             lymphocyte-associated protein-4, anti PD-1, and anti-PD-L1 therapeutic antibodies\r\n\r\n          -  Mutation in the BRAF oncogene. Patients with unknown BRAF status will be required to\r\n             undergo testing at a local laboratory and provide results at screening\r\n      ","sponsor":"Arcus Biosciences, Inc.","sponsor_type":"Industry","conditions":"Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: etrumadenant","description":"Dual adenosine receptor (A2aR and A2bR) antagonist"},{"intervention_type":"Drug","name":"Drug: zimberelimab","description":"Zimberelimab is a fully human anti-PD-1 monoclononal antibody"},{"intervention_type":"Drug","name":"Drug: mFOLFOX-6 regimen","description":"mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen"},{"intervention_type":"Drug","name":"Drug: bevacizumab","description":"Bevacizumab is administered as part of standard chemotherapy regimen"},{"intervention_type":"Drug","name":"Drug: regorafenib","description":"Regorafenib is adminstered as part of standard chemotherapy regimen"},{"intervention_type":"Drug","name":"Drug: AB680","description":"AB680 is a cluster of differentiated CD73 Inhibitor"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"From randomization until death from any cause (up to approximately 3-7 years)","description":"PFS as assessed by RECIST v1.1"},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"From randomization until death from any cause (up to approximately 3-7 years)","description":"ORR according to RECIST v1.1"},{"outcome_type":"primary","measure":"Objective Response Rate (ORR)","time_frame":"From randomization until death from any cause (up to approximately 3-7 years)","description":"ORR according to RECIST v1.1"}]}
{"nct_id":"NCT04590781","start_date":"2021-05-10","phase":"Phase 1/Phase 2","enrollment":142,"brief_title":"Safety and Efficacy of XmAb18087  Pembrolizumab in Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer","official_title":"A Phase 1b/2 Multiple-Dose Study to Evaluate the Safety and Efficacy of XmAb18087  Pembrolizumab in Subjects With Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer (DUET-1-02) Protocol","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-03-31","last_update":"2021-08-05","description":"This is a Phase 1b/2, multiple-dose study designed to describe safety and efficacy, and to assess PK and immunogenicity of XmAb18087 monotherapy and in combination with pembrolizumab in subjects with metastatic Merkel cell (MCC) or locoregional MCC that has recurred after locoregional therapy with surgery and/or radiation therapy, and XmAb18087 monotherapy in subjects with extensive-stage small cell lung cancer (SCLC) that has progressed after standard therapies.","other_id":"XmAb18087-02","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Able to provide written informed consent\r\n\r\n          -  Adult subjects  18 years\r\n\r\n          -  Disease measurable by RECIST 1.1 criteria using either computed tomography (CT) or\r\n             magnetic resonance imaging (MRI) scan\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  All subjects must have adequate archival tumor sample (slides or archival\r\n             formalin-fixed paraffin-embedded [FFPE] block[s] containing tumor that has not been\r\n             previously irradiated\r\n\r\n          -  Female subjects of childbearing potential must agree to use a highly effective method\r\n             of birth control during and for 4 weeks after completion of study. success), or sexual\r\n             abstinence\r\n\r\n          -  Fertile male subjects must be willing to practice a highly effective method of birth\r\n             control for the duration of the study and continuing for 4 weeks after the last dose\r\n             of XmAb18087 or pembrolizumab (when applicable\r\n\r\n          -  Able and willing to complete the entire study according to the study schedule\r\n\r\n        Additional Inclusion Criteria for Part A and Part B Cohorts:\r\n\r\n         Histologically or cytologically confirmed metastatic MCC or locoregional MCC that has\r\n        recurred following standard locoregional therapy with surgery and/or radiation therapy.\r\n\r\n        Additional Inclusion Criteria for Part A Cohorts:\r\n\r\n         Subjects must have progressed on or been ineligible for treatment with anti-PD1 or\r\n        anti-PDL1 therapy.\r\n\r\n        Additional Inclusion Criteria for Part B Cohorts:\r\n\r\n         Subjects must be eligible to receive pembrolizumab as standard of care.\r\n\r\n        Additional Inclusion Criteria for Part C Cohorts:\r\n\r\n        : Histologically or cytologically confirmed extensive-stage SCLC that has progressed\r\n        following standard therapies\r\n\r\n        -\r\n\r\n        Exclusion Criteria:\r\n\r\n        Additional Exclusion Criteria for Part B Cohorts: XmAb18087 in Combination with\r\n        Pembrolizumab In addition to the exclusion criteria in Section 8.6, subjects will be\r\n        excluded from Part B safety run-in and expansion cohorts administered XmAb18087 in\r\n        combination with pembrolizumab if they meet the following criteria:\r\n\r\n          -  Prior treatment with therapeutics directed at anti-programmed cell death 1 (anti-PD1)\r\n             or anti-programmed cell death ligand 1 (anti-PDL1)\r\n\r\n          -  Have severe hypersensitivity ( Grade 3) to pembrolizumab and/or any of its excipients\r\n      ","sponsor":"Xencor, Inc.","sponsor_type":"Industry","conditions":"Merkel Cell Carcinoma|Small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: XmAb18087","description":"Monoclonal bispecific antibody"},{"intervention_type":"Drug","name":"Drug: XmAb18087  Pembrolizumab","description":"XmAb18087  Pembrolizumab"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of treatment-emergent adverse events (safety), graded by CTCAE version 5.0","time_frame":"42 Days","description":"Determine the rates of treatment-emergent adverse events as graded by CTAE version 5.0"},{"outcome_type":"primary","measure":"ORR, CR rate and PR rate as assessed by RECIST 1.1 criteria (efficacy)","time_frame":"42 Days","description":"Determine the overall response rate (ORR), complete response (CR) rate and partial response (PR) rate, assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1"}]}
{"nct_id":"NCT04752332","start_date":"2021-05-10","phase":"Phase 3","enrollment":2450,"brief_title":"A Study of Abemaciclib (LY2835219) Plus Hormone Therapy in Participants With Early Breast Cancer","official_title":"eMonarcHER: A Randomized, Double Blind, Placebo-Controlled Phase 3 Study of Abemaciclib Plus Standard Adjuvant Endocrine Therapy in Participants With High-Risk, Node-Positive, HR+, HER2+ Early Breast Cancer Who Have Completed Adjuvant HER2-Targeted Therapy","primary_completion_date":"2025-05-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2033-02-28","last_update":"2021-09-21","description":"The main purpose of this study is to measure how well abemaciclib works in participants with early breast cancer who are taking hormone therapy after surgery. Participants must have breast cancer that is hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+). Your participation could last up to 10 years depending on how you and your tumor respond.","other_id":"17384","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Have confirmed HR+, HER2+ in initial diagnostic tissue, early invasive breast cancer\r\n             without evidence of disease recurrence or distant metastases\r\n\r\n          -  Have undergone definitive surgery of the primary breast tumor(s)\r\n\r\n          -  Have tumor tissue from breast (preferred) or lymph node\r\n\r\n          -  Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or\r\n             adjuvant setting per standard of care therapy\r\n\r\n          -  Have completed approximately nine months to one year of standard HER2-targeted therapy\r\n             without evidence of disease recurrence (neoadjuvant/adjuvant combined duration)\r\n\r\n          -  Have received one of the following eligible HER2-targeted adjuvant regimens AND be\r\n             randomized within 12 weeks of completing the regimen:\r\n\r\n               -  For participants treated with neoadjuvant therapy (chemotherapy administered with\r\n                  HER2-targeted therapy): Single agent adjuvant ado-trastuzumab emtansine or\r\n\r\n               -  For participants not treated with neoadjuvant therapy: Adjuvant pertuzumab with\r\n                  trastuzumab\r\n\r\n          -  Have high risk disease, defined by one of the following:\r\n\r\n               -  For participants treated with neoadjuvant therapy (as defined above):\r\n                  Pathologically detected axillary nodal disease in the surgical specimen\r\n\r\n               -  For participants not treated with neoadjuvant therapy: Axillary node positive\r\n                  disease meeting one of the following criteria:\r\n\r\n                    -  Pathological tumor involvement in greater than or equal to () four\r\n                       ipsilateral axillary lymph nodes OR\r\n\r\n                    -  Pathological tumor involvement in one to three ipsilateral axillary lymph\r\n                       node(s) and at least 1 of the following criteria:\r\n\r\n                         -  Histological Grade 3\r\n\r\n                         -  Primary invasive tumor size 5 centimeters determined pathologically\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Have breast cancer with any of the following features:\r\n\r\n               -  Disease recurrence or distant metastatic disease (including contralateral\r\n                  axillary lymph nodes)\r\n\r\n               -  Lymph node-negative status\r\n\r\n               -  Pathological complete response from any prior systemic treatments for early\r\n                  breast cancer\r\n\r\n               -  Inflammatory breast cancer\r\n\r\n          -  Have other medical conditions including:\r\n\r\n               -  Previous breast cancer (Exceptions: Ipsilateral ductal carcinoma in situ [DCIS]\r\n                  treated by locoregional therapy alone 5 years ago; contralateral DCIS treated by\r\n                  locoregional therapy at any time)\r\n\r\n               -  Other cancer being treated and/or not in complete remission within the last 5\r\n                  years (Exceptions: Appropriately treated non-melanomatous skin cancer or\r\n                  carcinoma in situ of cervix, bladder, or colon)\r\n\r\n               -  Females who are pregnant or lactating\r\n\r\n               -  History of venous thromboembolism\r\n\r\n               -  Other serious medical conditions\r\n\r\n          -  Have previously received treatment with:\r\n\r\n               -  Any cyclin-dependent kinase (CDK)4 and CDK6 inhibitor\r\n\r\n               -  Prior adjuvant treatment with immunotherapy, tucatinib, neratinib,\r\n                  investigational HER2 directed therapy, or trastuzumab deruxtecan for treatment of\r\n                  breast cancer\r\n\r\n               -  Endocrine therapy (ET) (i.e., tamoxifen, raloxifene or aromatase inhibitor) for\r\n                  breast cancer prevention (without diagnosis of breast cancer)\r\n\r\n               -  Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard\r\n                  of care therapy for their breast cancer at study enrollment\r\n      ","sponsor":"Eli Lilly and Company","sponsor_type":"Industry","conditions":"Breast Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: Abemaciclib","description":"Administered orally."},{"intervention_type":"Drug","name":"Drug: Standard Adjuvant ET","description":"Administered according to label instructions."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Administered orally."}],"outcomes":[{"outcome_type":"primary","measure":"Invasive Disease Free Survival (IDFS)","time_frame":"Randomization to Recurrence or Death from Any Cause (up to 10 Years)","description":"IDFS as defined by the STEEP System"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Randomization to Death from Any Cause (up to 10 Years)","description":"OS"},{"outcome_type":"secondary","measure":"Distant Relapse-Free Survival (DRFS)","time_frame":"Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years)","description":"DRFS"},{"outcome_type":"secondary","measure":"Percentage of Participants with Central Nervous System (CNS) Metastases as First Site of Disease Recurrence","time_frame":"Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years)","description":"Percentage of Participants with CNS Metastases as First Site of Disease Recurrence"},{"outcome_type":"secondary","measure":"Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score","time_frame":"Cycle 1 up to end of Year 4","description":"EORTC QLQ-C30 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms."},{"outcome_type":"secondary","measure":"Change from Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index Score","time_frame":"Cycle 1 up to end of Year 4","description":"The EQ-5D is a self-administered questionnaire that participants complete to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 5 (no problem, slight problems, moderate problems, severe problems, and extreme problems/unable to, respectively). These combinations of attributes were converted into a weighted Health State Index score; the possible values for the Health State Index score range from less than 0 (0 equals health state of \"dead\"; severe problems in all 5 dimensions) to 1.0 (full health; no problem in any dimension). Higher score indicates better health state."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib","time_frame":"Day 1 of Cycles 1-3 (Cycle = 28 days)","description":"PK: Mean Steady State Concentrations of Abemaciclib"}]}
{"nct_id":"NCT04830137","start_date":"2021-05-05","phase":"Phase 1","enrollment":130,"brief_title":"A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies","official_title":"A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies","primary_completion_date":"2023-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-11-30","last_update":"2021-08-09","description":"This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-2127 in patients with advanced B-cell malignancies.","other_id":"NX-2127-001","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients must be  18 years of age\r\n\r\n          -  Patients must have measurable disease per disease-specific response criteria\r\n\r\n          -  Patients with indolent forms of NHL must meet the criteria requiring systemic\r\n             treatment (i.e., iwCLL, IWG, or Lugano Classification of Lymphoma response criteria)\r\n\r\n          -  Patients with transformed lymphoma are eligible for the study with the exception of\r\n             those who have Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma\r\n             prior to planned start of study drug\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  Adequate organ and bone marrow function, in the absence of growth factors\r\n\r\n          -  Patients of child-bearing potential must use adequate contraceptive measures to avoid\r\n             pregnancy for the duration of the study as defined in the protocol\r\n\r\n        Inclusion Criteria for Patients in Phase 1a:\r\n\r\n          -  Have histologically confirmed R/R CLL, SLL, WM, MCL, and MZL, FL(grade 1 - 3b), and\r\n             DLBCL (High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements and\r\n             high-grade B-cell lymphoma NOS)\r\n\r\n          -  Received at least 2 prior systemic therapies (or 1 prior therapy for patients with WM)\r\n             and have no other therapies known to provide clinical benefit\r\n\r\n          -  Must require systemic therapy\r\n\r\n        Inclusion Criteria for Patients in Phase 1b:\r\n\r\n          -  Must have one of the following histologically documented R/R B-cell malignancies:\r\n\r\n               -  CLL/SLL with no BTK C481 mutation whose disease has failed treatment with a BTKi;\r\n\r\n               -  BTK C481 mutation-positive CLL/SLL whose disease has failed treatment with a\r\n                  BTKi;\r\n\r\n               -  MCL or MZL whose disease has failed treatment with BTKi and an anti-CD20\r\n                  mAb-based regimen or WM whose disease has failed treatment with BTKi\r\n\r\n               -  FL (grade 1 - 3b) whose disease has failed treatment with anti-CD20 mAb-based\r\n                  regimen;\r\n\r\n               -  DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and\r\n                  an anthracycline (either progressed post stem cell transplant or\r\n                  transplant-ineligible)\r\n\r\n                    -  DLBCL histologies include high-grade B-cell lymphoma, with MYC and BCL2\r\n                       and/or BCL6 rearrangements and high-grade B-cell lymphoma NOS\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of CNS lymphoma/leukemia in remission for less than 2 years\r\n\r\n          -  Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia\r\n\r\n          -  History of known/suspected other autoimmune disease (exception(s): patients with\r\n             vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism\r\n             that is clinically euthyroid at screening are allowed.)\r\n\r\n          -  Unable to swallow capsules or have a condition that may interfere in the delivery,\r\n             absorption, or metabolism of the study drug\r\n\r\n          -  Bleeding diathesis, or other known risk for acute blood loss\r\n\r\n          -  Patients requiring ongoing treatment with chronic, therapeutic anticoagulation with\r\n             warfarin or patients treated with dual anti-platelet therapy and vitamin K antagonists\r\n\r\n          -  Prior radiotherapy within 2 weeks of planned start of study drug (excluding limited\r\n             palliative radiation)\r\n\r\n          -  Toxicities from previous anticancer therapies must have resolved to baseline levels or\r\n             to Grade 1 (except for alopecia, hypothyroidism with adequate replacement therapy,\r\n             hypopituitarism with adequate replacement therapy, peripheral neuropathy or\r\n             hematologic parameters meeting inclusion criteria).\r\n\r\n          -  Active known second malignancy with the exception of any of the following:\r\n\r\n               -  Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or\r\n                  in situ cervical cancer;\r\n\r\n               -  Adequately treated Stage I cancer from which the patient is currently in\r\n                  remission and has been in remission for  2 years;\r\n\r\n               -  Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen <\r\n                  10 ng/mL; or\r\n\r\n               -  Any other cancer from which the patient has been disease-free for  2 years\r\n\r\n          -  Patient has had major surgery (e.g. requiring general anesthesia) within 4 weeks\r\n             before the planned first dose of study drug\r\n\r\n          -  Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: patients with\r\n             well-controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) are eligible.\r\n\r\n          -  Current active liver disease from any cause\r\n\r\n          -  Active viral reactivation (e.g., CMV or EBV)\r\n\r\n          -  Use of systemic corticosteroids (> 20 mg/day prednisone or equivalent)\r\n\r\n          -  Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of\r\n             myocardial infarction within 6 months of planned start of study drug\r\n\r\n          -  Patient is taking strong or moderate cytochrome P450 3A (CYP3A) inducers or inhibitors\r\n             or inhibitors of P-glycoprotein\r\n      ","sponsor":"Nurix Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Chronic Lymphocytic Leukemia (CLL)|Small Lymphocytic Lymphoma (SLL)|Waldenstrom Macroglobulinemia (WM)|Mantle Cell Lymphoma (MCL)|Marginal Zone Lymphoma (MZL)|Follicular Lymphoma (FL)|Diffuse Large B-cell Lymphoma (DLBCL)","interventions":[{"intervention_type":"Drug","name":"Drug: NX-2127","description":"Oral NX-2127"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants with Protocol Specified Dose-Limiting Toxicities","time_frame":"10 months","description":"Phase 1a"},{"outcome_type":"primary","measure":"To establish the MTD and/or recommended Phase 1b dose of NX-2127","time_frame":"10 months","description":"Phase 1a"},{"outcome_type":"primary","measure":"To evaluate the clinical activity of NX-2127 at the recommended Phase 1b dose based on overall response rate (ORR) as assessed by the Investigator","time_frame":"Up to 24 months","description":"Phase 1b"},{"outcome_type":"primary","measure":"Number of Participants with Adverse Events and Clinical Laboratory Abnormalities","time_frame":"Up to 3 years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration","time_frame":"Up to 3 years","description":"Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment"},{"outcome_type":"secondary","measure":"Duration of response (DOR) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) as assessed by the Investigator","time_frame":"Up to 3 Years","description":"Phase 1a/1b"},{"outcome_type":"secondary","measure":"Overall survival (OS) as assessed by the Investigator","time_frame":"Up to 24 months","description":"Phase 1b"},{"outcome_type":"secondary","measure":"To further evaluate the safety and tolerability of NX-2127 by collecting adverse events, treatment emergent adverse events, and incidence of all deaths","time_frame":"Up to 24 months","description":"Phase 1b"},{"outcome_type":"secondary","measure":"Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator","time_frame":"Up to 3 years","description":"Phase 1a/1b"}]}
{"nct_id":"NCT04873362","start_date":"2021-05-04","phase":"Phase 3","enrollment":1700,"brief_title":"A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy","official_title":"A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy","primary_completion_date":"2025-12-18","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2034-10-26","last_update":"2021-09-14","description":"This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes.","other_id":"WO42633","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed invasive breast carcinoma\r\n\r\n          -  Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive\r\n             breast cancer\r\n\r\n          -  Centrally confirmed PD-L1 and hormone receptor status\r\n\r\n          -  Clinical stage at disease presentation: cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0\r\n             (participants with cT1mi/T1a/T1b/N0 are not eligible)\r\n\r\n          -  Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane\r\n             and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are\r\n             permitted)\r\n\r\n          -  <=12 weeks between primary surgery and randomization\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\r\n\r\n          -  Screening left ventricular ejection fraction (LVEF) >= 50% and no decrease in LVEF by\r\n             >15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF >=\r\n             55%\r\n\r\n          -  Life expectancy >= 6 months\r\n\r\n          -  Adequate hematologic and end organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Stage IV breast cancer\r\n\r\n          -  An overall response of disease progression according to the investigator at the\r\n             conclusion of preoperative systemic therapy\r\n\r\n          -  Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors\r\n\r\n          -  History of exposure to various cumulative doses of anthracyclines\r\n\r\n          -  History of other malignancy within 5 years prior to screening, except for\r\n             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,\r\n             Stage I uterine cancer, or ductal carcinoma in situ (DCIS)\r\n\r\n          -  Current grade >=2 peripheral neuropathy\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis\r\n\r\n          -  History of or active autoimmune disease or immune deficiency\r\n\r\n          -  Treatment with immunostimulatory or immunosuppressive agents\r\n\r\n          -  Cardiopulmonary dysfunction\r\n\r\n          -  Any known active liver disease\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab","description":"Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug."},{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab will be administered at a dose of 1200 mg every three weeks (Q3W) for 14 cycles."},{"intervention_type":"Drug","name":"Drug: Trastuzumab Emtansine","description":"Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Placebo matched to atezolizumab will be administered at a dose of 1200 mg Q3W for 14 cycles."}],"outcomes":[{"outcome_type":"primary","measure":"Invasive Disease-free Survival (IDFS)","time_frame":"From randomization up to approximately 6 years","description":"IDFS event is defined as the time from randomization to the first occurrence of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, death from any cause."},{"outcome_type":"secondary","measure":"IDFS Including Second Primary Non-breast Invasive Cancer","time_frame":"From baseline up to 10 years"},{"outcome_type":"secondary","measure":"Disease-free Survival (DFS)","time_frame":"From baseline up to 10 years"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"From baseline up to 10 years"},{"outcome_type":"secondary","measure":"Distant Recurrence-free Interval (DRFI)","time_frame":"From baseline up to 10 years"},{"outcome_type":"secondary","measure":"Number of Participants with Clinically Meaningful Deterioration in Global Health Status/Quality of Life (GHS/QoL) Physical, Role, and Cognitive Function","time_frame":"From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)","description":"Clinically Meaningful Deterioration will be Measured by Scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ C30)"},{"outcome_type":"secondary","measure":"Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30","time_frame":"From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)","description":"The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms."},{"outcome_type":"secondary","measure":"Mean Change From Baseline Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30","time_frame":"From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)","description":"The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms."},{"outcome_type":"secondary","measure":"Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)","time_frame":"From baseline up to 10 years"},{"outcome_type":"secondary","measure":"Maximum Serum Concentrations (Cmax) for Atezolizumab","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 pre-infusion (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"},{"outcome_type":"secondary","measure":"Cmax for Trastuzumab Emtansine","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"},{"outcome_type":"secondary","measure":"Cmax for Total Trastuzumab","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"},{"outcome_type":"secondary","measure":"Cmax for DM1","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)","description":"DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine"},{"outcome_type":"secondary","measure":"Minimum Serum Concentrations (Cmin) for Atezolizumab","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"},{"outcome_type":"secondary","measure":"Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"},{"outcome_type":"secondary","measure":"Percentage of Participants with ADAs to Trastuzumab Emtansine","time_frame":"Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)"}]}
{"nct_id":"NCT04700072","start_date":"2021-05-03","phase":"Phase 1/Phase 2","enrollment":300,"brief_title":"Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)","official_title":"A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02D","primary_completion_date":"2030-04-03","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2030-04-03","last_update":"2021-09-16","description":"Substudy 02D is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) nave or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.","other_id":"3475-02D","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":120,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma\r\n\r\n          -  Is neurologically asymptomatic from brain metastases and has not received systemic\r\n             corticosteroid therapy in the 10 days prior to beginning study intervention\r\n\r\n          -  Has not received more than 3 lines of therapy for metastatic melanoma\r\n\r\n          -  Male participants are abstinent from heterosexual intercourse or agree to use\r\n             contraception during the intervention period\r\n\r\n          -  Female participants are not pregnant or breastfeeding and are either not a woman of\r\n             child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective\r\n             or are abstinent from heterosexual intercourse during the intervention period and for\r\n             at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab,\r\n             or 30 days after the last dose of lenvatinib, whichever occurs last\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within\r\n             10 days before the first dose of study intervention\r\n\r\n          -  Has current or history of known leptomeningeal involvement\r\n\r\n          -  Has received stereotactic or highly conformal radiotherapy within 2 weeks before the\r\n             start of dosing\r\n\r\n          -  Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the\r\n             first dose of study drug\r\n\r\n          -  Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS)\r\n             metastasis\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known additional malignancy that is progressing or requires active treatment\r\n             within the past 2 years\r\n\r\n          -  Has ocular melanoma\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in the past 2\r\n             years\r\n\r\n          -  Has known history of immunodeficiency virus (HIV)\r\n\r\n          -  Has known history of hepatitis B or known hepatitis C virus\r\n\r\n          -  Has a history of (noninfectious) pneumonitis that required steroids or current\r\n             pneumonitis\r\n\r\n          -  Has received prior systemic anticancer therapy within 4 weeks prior to\r\n             randomization/allocation\r\n\r\n          -  Has a history of whole brain irradiation\r\n\r\n          -  Has received prior radiotherapy within 2 weeks of first dose of study intervention\r\n\r\n          -  Has had major surgery <3 weeks prior to first dose of study intervention\r\n\r\n          -  Has received a live or live attenuated vaccine within 30 days prior to the first dose\r\n             of study intervention\r\n\r\n          -  Has had an allogeneic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Melanoma","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Administered via IV infusion at a specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Quavonlimab","description":"Administered via IV infusion at a specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Administered via oral capsule at a specified dose on specified days"}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of participants who experience an adverse event (AE)","time_frame":"Up to ~28 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported."},{"outcome_type":"primary","measure":"Percentage of participants who discontinue study treatment due to an AE","time_frame":"Up to ~24 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)","time_frame":"Up to ~30 months","description":"ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1","time_frame":"Up to ~30 months","description":"For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of ≥1 new lesion is also considered PD. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ."},{"outcome_type":"secondary","measure":"Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)","time_frame":"Up to ~30 months","description":"BMRR is defined as the percentage of participants in the analysis population who achieve a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids and stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status). Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases."},{"outcome_type":"secondary","measure":"Brain metastasis duration of response (BM-DOR) per RANO-BM","time_frame":"Up to ~30 months","description":"For participants in the analysis population who demonstrate a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids, stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status), DOR is defined as the time from first documented CR or PR until PD or death due to any cause, whichever occurs first. Per RANO-BM, PD is defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm in ≥1 lesion. Unequivocal increase in non-target lesions, the appearance of ≥1 new lesion or worsening of clinical status is also considered PD. Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) per RECIST 1.1","time_frame":"Up to ~30 months","description":"PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ."}]}
{"nct_id":"NCT04856371","start_date":"2021-04-30","phase":"Phase 1","enrollment":228,"brief_title":"Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer","official_title":"A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer","primary_completion_date":"2022-03-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2022-12-31","last_update":"2021-04-23","description":"This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET  CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.","other_id":"CYH33-G103","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Main Inclusion Criteria:\r\n\r\n          1. Provide informed consent voluntarily.\r\n\r\n          2. Male and female patients  18 years of age.\r\n\r\n          3. Patient must have a histologically or cytologically documented locally advanced,\r\n             recurrent or metastatic breast cancer.\r\n\r\n          4. In case of women, both premenopausal and postmenopausal patients can be enrolled in\r\n             the study.\r\n\r\n          5. Confirmed diagnosis of HR+, HER2- breast cancer.\r\n\r\n          6. For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be\r\n             enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are\r\n             required.\r\n\r\n          7. Patient must have evidence of disease radiological progression after previous\r\n             endocrine therapy, or other systemic therapy.\r\n\r\n          8. Patient has measurable disease per RECIST v1.1.\r\n\r\n          9. ECOG  1.\r\n\r\n         10. Patient must have adequate organ and bone marrow function.\r\n\r\n        Main Exclusion Criteria:\r\n\r\n          1. Previously received any anticancer therapy within 28 days or 5 times of half-lives\r\n             prior to the first dose of the study treatment.\r\n\r\n          2. Previously received treatment with any PI3K inhibitor, AKT inhibitor, or mTOR\r\n             inhibitor.\r\n\r\n          3. Radical radiation therapy within 4 weeks prior to the first dose of the study\r\n             treatment.\r\n\r\n          4. Patient with an established diagnosis of diabetes mellitus.\r\n\r\n          5. Any other concurrent disease with potential risk of insulin resistance or current use\r\n             of medication with potential risk of insulin resistance.\r\n\r\n          6. Patient with clinically significant cardiovascular disease.\r\n      ","sponsor":"Haihe Biopharma Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: CYH33","description":"Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle."},{"intervention_type":"Drug","name":"Drug: Fulvestrant","description":"Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1, 15 on Cycle 1 (28-day cycle) and Day 1 at each 28-day cycle thereafter."},{"intervention_type":"Drug","name":"Drug: Letrozole","description":"Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle."},{"intervention_type":"Drug","name":"Drug: Palbociclib","description":"Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Dose Limiting Toxicities (DLT)","time_frame":"28 days","description":"Incidence rate of DLT in the first cycle (of 28 days)."},{"outcome_type":"secondary","measure":"Safety and tolerability","time_frame":"30 months","description":"Type, incidence, duration, severity and seriousness of adverse events (AEs)."},{"outcome_type":"secondary","measure":"Preliminary efficacy-ORR","time_frame":"30 months","description":"Tumor objective response rate (ORR) assessed by RECIST v1.1"},{"outcome_type":"secondary","measure":"Preliminary efficacy-CBR","time_frame":"30 months","description":"Clinical benefit rate (CBR) assessed by RECIST v1.1"},{"outcome_type":"secondary","measure":"Preliminary efficacy-PFS","time_frame":"30 months","description":"Progression Free Survival (PFS) assessed by RECIST v1.1"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - AUC","time_frame":"20 months","description":"Measure the variation of concentration in blood plasma as a function of time"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - C trough","time_frame":"20 months","description":"Measure the minimum (trough) plasma concentration"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - Cmax","time_frame":"20 months","description":"Measure the maximum (peak) plasma concentration"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - Tmax","time_frame":"20 months","description":"Measure of time to reach maximum (peak) plasma concentration"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - CL/F","time_frame":"20 months","description":"Measure apparent total clearance(s) from plasma after administration"},{"outcome_type":"secondary","measure":"Pharmacokinetic measures - Vz/F","time_frame":"20 months","description":"Measure apparent volume of distribution during terminal phase"},{"outcome_type":"secondary","measure":"Assess downstream effects of PI3K pathway inhibition on blood glucose","time_frame":"20 months","description":"Pre- and post-treatment of blood glucose"},{"outcome_type":"secondary","measure":"Assess downstream effects of PI3K pathway inhibition on C peptide","time_frame":"20 months","description":"Pre- and post-treatment of C peptide"},{"outcome_type":"secondary","measure":"Assess the changes of biomarker-PIK3CA","time_frame":"20 months","description":"Pre- and post-treatment PIK3CA changes in ctDNA samples."},{"outcome_type":"secondary","measure":"Assess the changes of biomarker-PTEN","time_frame":"20 months","description":"Pre- and post-treatment PTEN changes in ctDNA samples."},{"outcome_type":"secondary","measure":"Assess the changes of biomarker-KRAS","time_frame":"20 months","description":"Pre- and post-treatment KRAS changes in ctDNA samples."}]}
{"nct_id":"NCT04853498","start_date":"2021-04-30","phase":"Phase 1","enrollment":120,"brief_title":"A Study to Evaluate the Tolerance and Pharmacokinetics of TQB3720 Tablets","official_title":"A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance and Pharmacokinetics of TQB3720 Tablets","primary_completion_date":"2023-05-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-05-30","last_update":"2021-04-21","description":"This study is conducted to investigate the pharmacokinetic and safety profiles of TQB3720 in patients with metastatic castration-resistant prostate cancer.","other_id":"TQB3720-I-01","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":18,"maximum_age":80,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Histologically or cytologically confirmed prostate carcinoma. 2.Eastern Cooperative\r\n             Oncology Group (ECOG) performance status score of 0 to 2; Life expectancy 12 weeks.\r\n\r\n             3.Testosterone levels < 50 ng/dL. 4. Has received 1 previous regimens for metastatic\r\n             castration-resistant prostate cancer.\r\n\r\n             5.Male subjects should agree to use an adequate method of contraception starting with\r\n             signing ICF through 6 months after the last dose of study.\r\n\r\n             6.Understood and signed an informed consent form.\r\n\r\n        Exclusion Criteria:\r\n\r\n        -1.Has symptomatic brain metastases or control of symptoms < 1 month. 2.Has other\r\n        malignancies within 3 years. 3.Has used second-generation androgen receptor antagonists. 4.\r\n        Abnormal liver function. 5. Abnormal renal function. 6. Has received any other\r\n        investigational drug within 30 days weeks before first dose.\r\n\r\n        7. According to the judgement of the researchers, there are other factors that subjects are\r\n        not suitable for the study.\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Metastatic Castration-resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TQB3720","description":"This is an androgen receptor antagonists."}],"outcomes":[{"outcome_type":"primary","measure":"Maximum tolerated dose (MTD)","time_frame":"Baseline up to 28 days","description":"MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT."},{"outcome_type":"secondary","measure":"Cmax","time_frame":"0hour, 2hour, 4hour, 8hour, 12hour, 24hour, 36hour, 48hour, 72hour, 96hour,120hour post-dose on single dose; Hour 0 of day 8、day 15、day 22；0 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour post-dose on multiple dose of day 28; Hour 0 of day 42 and day 56.","description":"Cmax is the maximum plasma concentration of TQB3720 or metabolite(s)."},{"outcome_type":"secondary","measure":"Tmax","time_frame":"0hour, 2hour, 4hour, 8hour, 12hour, 24hour, 36hour, 48hour, 72hour, 96hour,120hour post-dose on single dose; Hour 0 of day 8、day 15、day 22；0 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour post-dose on multiple dose of day 28; Hour 0 of day 42 and day 56.","description":"To characterize the pharmacokinetics of TQB3720 by assessment of time to reach maximum plasma concentration."},{"outcome_type":"secondary","measure":"AUC0-t","time_frame":"0hour, 2hour, 4hour, 8hour, 12hour, 24hour, 36hour, 48hour, 72hour, 96hour,120hour post-dose on single dose; Hour 0 of day 8、day 15、day 22；0 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour post-dose on multiple dose of day 28; Hour 0 of day 42 and day 56.","description":"To characterize the pharmacokinetics of TQB3720 by assessment of area under the plasma concentration time curve from zero to infinity."}]}
{"nct_id":"NCT04843098","start_date":"2021-04-30","phase":"Phase 1/Phase 2","enrollment":108,"brief_title":"Study of TL117 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma","official_title":"Phase I/II Study of the PI3K Inhibitor TL117 Alone and in Combination With Paclitaxel in Patients With Relapsed/Metastatic Squamous Cell Carcinoma of the Head and Neck","primary_completion_date":"2024-01-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-01-31","last_update":"2021-04-13","description":"The purpose of this study is to assess the safety, pharmacokinetic and efficacy of TL117 plus paclitaxel in patients with recurrent or metastatic head and neck cancer.","other_id":"TL-117-202001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. 18-70 years old for Phase 1a, 18-75 years old for Phase 1b and 2;\r\n\r\n          2. Histologically and/or cytologically confirmation of recurrent/metastatic squamous cell\r\n             carcinoma of the head and neck;\r\n\r\n          3. At least one evaluable or measurable tumor lesion;\r\n\r\n          4. Adequate performance status;\r\n\r\n          5. A minimum life expectancy of > 3 months;\r\n\r\n          6. Adequate cardiac, kidney, and liver function;\r\n\r\n          7. Willingness of all subjects of childbearing potential to use acceptable methods of\r\n             birth control;\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Any chemotherapy, radiotherapy, targeted therapy, immunotherapy, endocrine therapy and\r\n             other systematic anti-tumor therapies within 4 weeks prior to the first dose of the\r\n             study drug (some exceptions apply)\r\n\r\n          2. Prior or current PI3K inhibitor therapy;\r\n\r\n          3. Type 1 or type 2 diabetes requiring antihyperglycemic medication;\r\n\r\n          4. Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks\r\n             prior to the first dose, or required elective surgery during the study period;\r\n\r\n          5. Any unresolved toxicities from prior therapy greater than Grade 1;\r\n\r\n          6. Inability to swallow, or serious gastrointestinal absorption conditions;\r\n\r\n          7. History of immunodeficiency;\r\n\r\n          8. Active central nervous system metastases;\r\n\r\n          9. Active hepatitis B or C virus infection;\r\n\r\n         10. Uncontrolled active infection;\r\n\r\n         11. Serious cardiovascular disease\r\n\r\n         12. Clinically uncontrollable effusion in the third space;\r\n\r\n         13. Known allergy and/or contraindications to paclitaxel;\r\n\r\n         14. Known alcohol or drug dependence;\r\n\r\n         15. Mental disorders or poor compliance;\r\n\r\n         16. Pregnant or lactating women;\r\n      ","sponsor":"Suzhou Junde Biotechnology Co., Ltd","sponsor_type":"Industry","conditions":"Head and Neck Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: TL117","description":"TL117 capsules orally once daily"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 28-day treatment cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Phase Ia -Dose Limiting Toxicity (DLT) of TL117 treatment","time_frame":"From time of the first dosing to time of Cycle 1 Day 28（each cycle is 28 days）","description":"Per DLT criteria as defined in protocol"},{"outcome_type":"primary","measure":"Phase Ib -Dose Limiting Toxicity (DLT) of TL117 plus paclitaxel combination treatment","time_frame":"From time of the first dosing to time of Cycle 1 Day 28（each cycle is 28 days）","description":"Per DLT criteria as defined in protocol"},{"outcome_type":"primary","measure":"Phase II - Objective response rate (ORR)","time_frame":"Every 8 weeks from date of first treatment until date of last treatment up to 12 months","description":"Objective response rate (ORR): percentage of patients with best overall response of complete response (CR) and partial response (PR) according to RECIST v1.1."}]}
{"nct_id":"NCT04728035","start_date":"2021-04-30","phase":"Phase 1","enrollment":136,"brief_title":"Study of Irinotecan Liposome Injection in Patients With Advanced Breast Cance","official_title":"A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Irinotecan Liposome Injection in Patients With Advanced Breast Cancer","primary_completion_date":"2023-04-30","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2024-04-30","last_update":"2021-01-29","description":"This study is an open-label, single-arm, phase I study of irinotecan liposome injection in patients with advanced breast cancer. The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics of irinotecan liposome injection in patients with advanced breast cancer.","other_id":"HE072-CSP-002","allocation":"Non-Randomized","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        All patients 1.Female aged between 18 and 75 years.\r\n\r\n        2.Histologically or cytologically confirmed breast cancer.\r\n\r\n        3.At least one measurable lesion according to RECIST 1.1.\r\n\r\n        4.The time interval between the end of the last anti-tumor treatment and the first\r\n        administration of irinotecan liposome injection is restricted as follows:\r\n\r\n        (1) More than 6 weeks for nitrosoureas (such as carmustine, lomustine, etc.) or mitomycin\r\n        C.\r\n\r\n        (2) More than 3 weeks for cytotoxic chemotherapeutics, immunotherapy such as PD-1/PD-L1 and\r\n        biotherapy.\r\n\r\n        (3) More than 2 weeks (five half-lives, whichever is longer) for oral fluorouracil, oral\r\n        small molecule targeted drugs, and endocrine therapy.\r\n\r\n        (4) More than 2 weeks for Radiotherapy. (5) More than 2 Weeks for traditional Chinese\r\n        medicine with anti-tumor indications.\r\n\r\n        5.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.\r\n\r\n        6.Life expectancy >3 months.\r\n\r\n        7.Patient should not receive blood transfusion or supportive care (eg. EPO, G-CSF or\r\n        others) within 14 days before the initiate dose, and laboratory test should meet the\r\n        following criteria: neutrophile count 1.510^9/L platelet count 10010^9/L hemoglobin 90\r\n        g/L or 5.6 mmol/L serum creatinine 1.5ULN and creatinine clearance rate 50 mL/min total\r\n        bilirubin 1ULN AST and ALT 2.5ULN\r\n\r\n        8.Patient with reproductive potential must agree to use adequate contraception from the\r\n        signing of informed consent to at least 6 months after the trial completion and have a\r\n        negative serum pregnancy test within 7 days before enrollment.\r\n\r\n        9.Ability to understand and the willingness to sign a written informed consent.\r\n\r\n        Additional criteria for dose escalation and cohort 1 in dose expansion\r\n\r\n        1.Meet the molecular classification criteria for triple-negative breast cancer.\r\n\r\n        2.Patients with locally recurrent or metastatic disease who have received at least two\r\n        prior chemotherapeutic regimens for breast cancer and had failed to prior chemotherapy due\r\n        to progression or intolerable toxicity:\r\n\r\n        (1)Early neoadjuvant or adjuvant chemotherapy for localized disease that progresses to\r\n        unresectable locally advanced or metastatic disease within 12 months after completion is\r\n        one of the permitted previous chemotherapy regimens.\r\n\r\n        (2)PARP inhibitor for patients with germline BRCA1/BRCA2 mutations who have been treated\r\n        with approved PARP inhibitors, is one of the permitted prior chemotherapy regimens.\r\n\r\n        3.Previous treatment with taxanes and anthracyclines was required regardless of the stage\r\n        of disease (neoadjuvant, adjuvant or palliative). Those who have contraindications or\r\n        intolerance to a certain drug above should receive at least one cycle of treatment with\r\n        this drug, and can be exempted from the requirements for the use of this drug.\r\n\r\n        Additional criteria for cohort 2 in dose expansion\r\n\r\n        1.HER2 negative breast cancer defined as 0 - 1+ by immunohistochemistry or FISH negative\r\n        result.\r\n\r\n        2.Evidence of new and/or progressive brain metastases following previous radiotherapy (WBRT\r\n        and/or SRS and/or gamma knife) and/or surgery.\r\n\r\n        3.At least one measurable brain lesion (10 mm on T1-weighted, gadolinium-enhanced magnetic\r\n        resonance imaging).\r\n\r\n        Exclusion Criteria\r\n\r\n          1. Patients who have received any investigational drug within 4 weeks of the first dose\r\n             of the study drug.\r\n\r\n          2. Patients who have undergone major organ surgery (excluding needle biopsy) or have\r\n             significant trauma within 4 weeks prior to the first dose of the study drug, or have a\r\n             schedule for major surgery during the trial.\r\n\r\n          3. Patients who have concomitant use of strong CYP3A4 inhibitors or inducers within 2\r\n             weeks prior to receiving the first dose of irinotecan liposome injection, or CYP3A4\r\n             inhibitors or UGT1A1 inhibitors within 1 week prior to receiving the first dose of\r\n             irinotecan liposome injection, or those who could not suspend the above drugs during\r\n             the study.\r\n\r\n          4. Patients who received systemic glucocorticoids (prednisone >10 mg/day or equivalent\r\n             dose of the similar drugs) or other immunosuppressive agents within 14 days before the\r\n             first dose of the study drug. Except for local, ocular, intra-articular, intranasal,\r\n             and inhaled glucocorticoids, short term use of glucocorticoids for preventive\r\n             treatment (e.g., prevention of contrast allergy). Cohort 2 in dose expansion is not\r\n             limited.\r\n\r\n          5. Patients who have received prior topoisomerase I inhibitor treatment, including\r\n             irinotecan or other investigational agents.\r\n\r\n          6. Known hypersensitivity (CTCAE 5.03) to any of the components of irinotecan liposome\r\n             injection, or other liposomal products.\r\n\r\n          7. Patients with central Nervous System (CNS) metastasis meet any of the following\r\n             criteria: Cohort 2 in dose expansion is not limited.\r\n\r\n        (1)Patients who have developed new or progressive brain metastasis following cranial\r\n        radiation or surgery.\r\n\r\n        (2)Patients with the symptomatic Central Nervous System (CNS) metastasis who have used\r\n        cortisol, radiotherapy, dehydration drugs, etc. to control symptoms in the past two weeks.\r\n\r\n        (3)Patients with carcinomatous meningitis.\r\n\r\n        (4)Patients with brainstem (midbrain, pons, medulla oblongata) metastasis.\r\n\r\n        (5)Patients have other evidence indicates that the patient's central nervous system\r\n        metastasis or meningeal metastasis has not been controlled and is judged unsuitable for\r\n        enrollment by the investigator.\r\n\r\n        8.Patients who have pulmonary lymphatic dissemination and metastasis, leading to dyspnea at\r\n        rest, may need to be combined with other treatments, such as oxygen inhalation, which is\r\n        judged not suitable for enrollment by the investigator.\r\n\r\n        9.Prior radiation therapy encompassing more than 30% of bone marrow.\r\n\r\n        10.Patients have unresolved adverse reactions > grade 1 (CTCAE 5.0) from previous\r\n        anti-tumor treatment (except for the peripheral neuropathy < grade 2, alopecia, and other\r\n        toxicity judged no safety risk by investigators).\r\n\r\n        11.History of autoimmune disease, immunodeficiency (including HIV test positive), or other\r\n        acquired or congenital immunodeficiency, or organ transplantation.\r\n\r\n        12.Patients with known Hepatitis B Virus (HBV DNA>2000 IU/ml), Hepatitis C Virus (anti-HCV\r\n        positive), or other uncontrolled active infections.\r\n\r\n        13.Chronic gastrointestinal dysfunction with diarrhea as the main symptom, such as Crohn's\r\n        disease, ulcerative colitis, malabsorption or Diarrhea  grade 1, intestinal obstruction,\r\n        or other gastrointestinal diseases of clinical significance as judged by the investigators.\r\n\r\n        14.Previous malignancies in the past five years (except basal cell carcinoma, squamous cell\r\n        carcinoma, superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of\r\n        cervical, or of others that have been radically resected and have not recurred).\r\n\r\n        15.History of serious cardiovascular disease, including but not limited to:\r\n\r\n          1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias\r\n             requiring clinical intervention, II-III degree atrioventricular block, etc.\r\n\r\n          2. Patients with prolonged QT/QTc interval in baseline electrocardiogram (ECG) (QTcF >\r\n             480 ms, Fridericia formula: QTcF = QT/RR0.33, RR = 60/heart rate).\r\n\r\n          3. Patients with myocardial infarction, angina pectoris, coronary angioplasty or stent,\r\n             deep vein thrombosis, stroke within 6 months before enrollment.\r\n\r\n          4. Baseline echocardiography (ECHO) or cardiac radionuclide scanning (MUGA) techniques\r\n             showed left ventricular ejection fraction (LVEF)  50%, or NYHA grade  and above.\r\n\r\n          5. Poorly controlled hypertension (systolic blood pressure150 mmHg and/or diastolic\r\n             blood pressure 95 mmHg with optimal treatment.\r\n\r\n          6. Previous or current cardiomyopathy.\r\n\r\n          7. Patients with clinically significant abnormal electrocardiogram (ECG)according to the\r\n             investigator's assessment.\r\n\r\n        16. Uncontrolled third lacunar effusion, improper for enrollment by investigator's\r\n        assessment.\r\n\r\n        17. Patients with alcohol or drug dependence.\r\n\r\n        18. Pregnant or lactating women.\r\n\r\n        19.History of explicit neurological or psychiatric disorders, including epilepsy or\r\n        dementia.\r\n\r\n        20. Known medical condition that, in the investigator's opinion, would increase the risk\r\n        associated with study participation or study drug administration, or interfere with the\r\n        interpretation of safety results.\r\n      ","sponsor":"CSPC Ouyi Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Irinotecan Liposome Injection","description":"Irinotecan Liposome Injection"}],"outcomes":[{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS)","time_frame":"Up to six months after the last patient's first administration","description":"Time from date of the first dose to date of recorded disease progression or death, whichever occurs first."},{"outcome_type":"primary","measure":"Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)","time_frame":"Up to six months after the last patient's first administration","description":"The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0."},{"outcome_type":"primary","measure":"Dose limiting toxicity (DLT)","time_frame":"Up to 28 days post-product injection","description":"DLT will be assessed according to NCICTCAE v5.0."},{"outcome_type":"primary","measure":"Maximum Tolerated Dose (MTD, if available)","time_frame":"Up to 28 days post-product injection","description":"MTD was defined as the previous dose level at which 2 out of 6 patients experienced a DLT."},{"outcome_type":"primary","measure":"Recommended Phase 2 Dose (RP2D)","time_frame":"Up to the end of the part 1","description":"RP2D was defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability data collected during the dose escalation portion of the study."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to six months after the last patient's first administration","description":"The percentage of patients who achieve a complete response (CR) or partial response (PR) based on the modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)."},{"outcome_type":"secondary","measure":"CNS objective response rate (CNS ORR)","time_frame":"Up to six months after the last patient's first administration","description":"The percentage of patients who achieve a CR or PR based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) in Cohort 2 of dose expansion."},{"outcome_type":"secondary","measure":"CNS clinical benefit rate (CNS CBR)","time_frame":"Up to six months after the last patient's first administration","description":"The percentage of patients who achieve a CR, PR or SD based on RANO-BM in Cohort 2 of dose expansion."},{"outcome_type":"secondary","measure":"The Area under the concentration-time curve from time zero to infinity (AUCinf)","time_frame":"-30minutes~168hours","description":"AUCinf of total irinotecan,wrapped irinotecan, free irinotecan and SN-38 will be measured for the test product ."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Up to six months after the last patient's first administration","description":"The percentage of patients who achieve a CR, PR or stable disease (SD) based on the modified RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to six months after the last patient's first administration","description":"Time from first documented response (CR or PR whichever occurs first, based on investigator's assessment using RECIST 1.1) to date of disease progression or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to six months after the last patient's first administration","description":"Time from date of the first dose to date of death from any cause."},{"outcome_type":"secondary","measure":"The Maximum observed plasma concentration (Cmax)","time_frame":"-30 minutes~168 hours","description":"Cmax of total irinotecan，wrapped irinotecan, free irinotecan and SN-38 will be measured for the test product ."},{"outcome_type":"secondary","measure":"The terminal elimination half-life (T1/2)","time_frame":"-30 minutes~168 hours","description":"T1/2 of total irinotecan,wrapped irinotecan, free irinotecan and SN-38 will be measured for the test product."},{"outcome_type":"secondary","measure":"The time to maximum concentration (Tmax)","time_frame":"-30minutes~168 hours","description":"Tmax of total irinotecan,wrapped irinotecan, free irinotecan and SN-38 will be measured for the test product ."},{"outcome_type":"secondary","measure":"The Apparent volume of distribution (Vd)","time_frame":"-30 minutes~168 hours","description":"Vd of total irinotecan will be measured for the test product."},{"outcome_type":"other","measure":"UGT1A1 gene polymorphism and Topoisomerase I (Topo I) expression","time_frame":"Up to six months after the last patient's first administration","description":"UGT1A1 gene polymorphism and Topoisomerase I (Topo I) expression"}]}
{"nct_id":"NCT03866499","start_date":"2021-04-30","phase":"Phase 3","enrollment":294,"brief_title":"A Study of BPI-7711 Capsule in Non-small Cell Lung Cancer Patients","official_title":"A Randomized, Double-blind, Positive Controlled Phase III Study to Evaluate the Efficacy and Safety of BPI-7711 Capsule in Locally Advanced or Recurrent/Metastatic Treatment-nave Non-small Cell Lung Cancer Patients With EGFR Mutation","primary_completion_date":"2022-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-10-31","last_update":"2021-07-21","description":"A randomized, double-blind, positive controlled phase III study to evaluate the efficacy and safety of BPI-7711 capsule in locally advanced or recurrent/metastatic treatment-nave non-small cell lung cancer patients with EGFR mutation","other_id":"BPI-7711301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed non-small cell lung cancer.\r\n\r\n          -  The ECOG score of performance status is 0-1.\r\n\r\n          -  Locally advanced or recurrent metastatic NSCLC that has never received systemic\r\n             treatment.\r\n\r\n          -  According to RECIST1.1 criteria, there is at least 1 measurable lesion that has not\r\n             been previously irradiated.\r\n\r\n          -  Prior to enrollment, a central laboratory testing report has confirmed that the tumor\r\n             has one of two common EGFR mutations positive that are sensitive to EGFR-TKI therapy,\r\n             accompanied with or not accompanied with other EGFR mutation, with the exception of\r\n             exon 20 insertion.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previously received systemic treatment for locally advanced or recurrent metastatic\r\n             cancer.\r\n\r\n          -  Primary T790M mutation-positive patient.\r\n\r\n          -  Previous interstitial lung disease, drug-induced interstitial lung disease, radiation\r\n             pneumonia requiring hormonal therapy, or any clinically proven active interstitial\r\n             lung disease.\r\n\r\n          -  Known active infections such as hepatitis B, hepatitis C, and human immunodeficiency\r\n             virus.\r\n\r\n          -  Local radiation therapy is carried out within 1 week; more than 30% bone marrow\r\n             radiation therapy or extensive radiation therapy is performed within 4 weeks.\r\n\r\n          -   4 weeks from major surgery or  2 weeks from minor surgery.\r\n      ","sponsor":"Beta Pharma, Inc.","sponsor_type":"Industry","conditions":"NSCLC","interventions":[{"intervention_type":"Drug","name":"Drug: BPI-7711","description":"180 mg, oral, QD"},{"intervention_type":"Drug","name":"Drug: Gefitinib","description":"250 mg, oral, QD"},{"intervention_type":"Drug","name":"Drug: Placebo Tablet","description":"250 mg gefitinib placebo tablet, QD"},{"intervention_type":"Drug","name":"Drug: Placebo capsule","description":"180 mg BPI-7711 placebo capsule, QD"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival","time_frame":"up to approximately 16 months","description":"Progression-free survival evaluated by Blinded Independent Center Review"},{"outcome_type":"secondary","measure":"Progression-free survival","time_frame":"up to approximately 16 months","description":"Progression-free survival evaluated by investigators"},{"outcome_type":"secondary","measure":"Objective response rate","time_frame":"up to approximately 16 months","description":"Objective response rate"},{"outcome_type":"secondary","measure":"Best objective response","time_frame":"up to approximately 16 months","description":"Best objective response"},{"outcome_type":"secondary","measure":"Disease control rate","time_frame":"up to approximately 16 months","description":"Disease control rate"},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"up to approximately 16 months","description":"Duration of response"},{"outcome_type":"secondary","measure":"Overall survival","time_frame":"up to approximately 30 months","description":"Overall survival"}]}
{"nct_id":"NCT04815083","start_date":"2021-04-27","phase":"Phase 3","enrollment":370,"brief_title":"Fluorescence Imaging of Carcinoma During Breast Conserving Surgery","official_title":"A Prospective Multi-center Clinical Study Evaluating the Use of PD G 506 A and the Eagle V1.2 Imaging System for the Visualization of Carcinoma During Breast Conserving Surgery","primary_completion_date":"2022-11-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-31","last_update":"2021-05-28","description":"Breast conserving surgery (BCS) is performed on patients with breast cancer to resect and completely remove the cancer while conserving as much of the surrounding healthy tissue as possible. Current methods do not allow surgeons to determine the completeness of surgical resection in real-time. This often results in the need for a second surgical procedure, or in some cases more than two surgical procedures in order to have confidence that all cancer has been removed. This Phase 3 study will evaluate the safety and efficacy of the fluorescent imaging agent PD G 506 A for the real-time visualization of cancer during standard of care breast conserving surgery. PD G 506 A is an investigational drug which is converted in the body into a fluorescent molecule that accumulates in cancer cells. Patients receiving PD G 506 A will undergo standard of care breast conserving surgery followed by fluorescence imaging and removal of any potentially cancerous tissue left behind in the surgical cavity.","other_id":"SBI-CIP 20-002","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"Double","intervention_model_description":"Part A of the study is open-label. All patients in Part A will receive the investigational drug and will undergo standard of care breast conserving surgery (BCS) followed by fluorescence-guided resection. Part B of the study is randomized and placebo controlled; patients will be randomized to receive placebo + standard of care BCS alone or PD G 506 A + SoC BCS followed by fluorescence-guided resection.","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Female, 18 years or older\r\n\r\n          2. Histologically or cytologically confirmed primary breast cancer (includes invasive\r\n             lobular carcinoma, invasive ductal carcinoma, inflammatory breast cancer, papillary\r\n             breast cancer, adenoid cystic carcinoma of the breast, mucinous breast cancer,\r\n             metaplastic breast cancer, cribriform carcinoma and ductal carcinoma in situ, alone or\r\n             in combination with invasive disease)\r\n\r\n          3. Scheduled for a lumpectomy (including bilateral lumpectomy) of a breast malignancy\r\n             (eligibility for breast conserving surgery/partial mastectomy based on clinical\r\n             staging using TNM staging system (AJCC Cancer Staging Manual: Breast Cancer, 8th\r\n             Edition70).\r\n\r\n          4. Patient must have normal organ and bone marrow function and be appropriate surgical\r\n             candidate per site standard of care\r\n\r\n          5. Women of child-bearing potential must agree to use adequate contraception (hormonal or\r\n             barrier method of birth control, abstinence) starting the day entering the study, and\r\n             for the duration of the study period (until the Week 2 visit)\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Currently on (neo)adjuvant therapy to treat another cancer\r\n\r\n          2. Receiving or intended to receive neoadjuvant therapy to treat the primary breast\r\n             cancer (including chemotherapy, endocrine therapy and radiotherapy)\r\n\r\n          3. Stage 4 cancer, inclusive of metastatic disease\r\n\r\n          4. Non-invasive diseases of the breast (includes lobular carcinoma in situ, phyllodes and\r\n             Paget's disease of the breast)\r\n\r\n          5. Patients who have had previous surgery on the involved breast including breast\r\n             surgeries, mastectomies, breast reconstructions or implants\r\n\r\n          6. Patients for whom intraoperative frozen section analysis is planned\r\n\r\n          7. Patients who have not recovered from adverse events due an investigational\r\n             pharmaceutical or diagnostic agents administered more than 30 days prior to their\r\n             scheduled surgical procedure\r\n\r\n          8. History of hypersensitivity to ALA HCl or porphyrins\r\n\r\n          9. Known or documented personal or family history of porphyria\r\n\r\n         10. Patient has a recording of any parameter as defined below:\r\n\r\n               1. Bilirubin: Above upper limit of normal\r\n\r\n               2. Aspartate aminotransferase (SGOT): > 2.5 X institutional upper limit of normal\r\n\r\n               3. Alanine aminotransferase ( (SGPT): > 2.5 X institutional upper limit of normal\r\n\r\n         11. Patient has serum creatinine >1.5 times institutional upper limit of normal, OR\r\n             calculated creatinine clearance > 60 mL/min/1.73 m for patients with creatinine\r\n             levels above institutional normal.\r\n\r\n         12. Uncontrolled concurrent illness, that in the opinion of the Investigator would prevent\r\n             the patient from participation in the study, including but not limited to:\r\n\r\n               1. Ongoing or active infection;\r\n\r\n               2. Cardiovascular disease (e.g. symptomatic congestive heart failure, unstable\r\n                  angina pectoris, cardiac arrhythmia).\r\n\r\n         13. Patients who have the following collagen vascular diseases:\r\n\r\n               1. Lupus\r\n\r\n               2. Scleroderma\r\n\r\n         14. Use of an investigational drug within 30 days of their scheduled surgical procedure\r\n\r\n         15. Simultaneous use of other potentially phototoxic substances (such as St. John's wort,\r\n             griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides,\r\n             quinolones and tetracyclines), and topical preparations containing ALA for 24 hours\r\n             during the perioperative period.\r\n\r\n         16. Social or medical situations including uncontrolled psychiatric illnesses that would\r\n             in the opinion of the Investigator limit compliance with study requirements (e.g.\r\n             ability to travel for follow-up)\r\n\r\n         17. Patients who are pregnant or become pregnant (it is unknown if ALA HCl is teratogenic\r\n             or has abortifacient effects)\r\n\r\n         18. Patients who are breast feeding (there is an unknown but potential risk for adverse\r\n             events in nursing infants secondary to treatment of the mother with ALA HCl,\r\n             breastfeeding should be discontinued if the mother is treated with ALA HCl)\r\n\r\n         19. Inability to consent\r\n      ","sponsor":"SBI ALApharma Canada, Inc.","sponsor_type":"Industry","conditions":"Breast Neoplasm Female|Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Aminolevulinic Acid Hydrochloride","description":"PD G 506 A for oral solution (aminolevulinic acid [ALA] hydrochloride [HCl] granules for oral solution) is administered as a single dose (20 mg/kg body weight) approximately 3 hours (min 2 hours, max 4 hours) prior to anesthesia."},{"intervention_type":"Device","name":"Device: Eagle V1.2 Imaging System","description":"Fluorescence imaging camera and associated accessories used to view and capture fluorescence and white light images and videos of the surgical cavity and excised tissue specimens during the surgical procedure."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Oral placebo is administered as a single dose approximately 3 hours (min 2 hours, max 4 hours) prior to anesthesia."}],"outcomes":[{"outcome_type":"secondary","measure":"Patient-level diagnostic performance after fluorescence guided resection","time_frame":"2 weeks","description":"Patient-level sensitivity, PPV of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer"},{"outcome_type":"secondary","measure":"Patient-level diagnostic performance of PD G 506 A to detect residual cancer at the end of FGR with modified patient-level definitions","time_frame":"2 weeks","description":"Patient-level diagnostic performance characteristics of sensitivity, specificity, PPV and NPV to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR (using modified patient-level definitions)"},{"outcome_type":"primary","measure":"Positive margin conversion rate","time_frame":"2 weeks","description":"Percentage of patients with negative-margins following fluorescence-guided resection (FGR) among patients with positive margins following standard of care (SoC)"},{"outcome_type":"primary","measure":"Diagnostic performance (Specificity)","time_frame":"2 weeks","description":"Patient-level specificity to identify residual carcinoma"},{"outcome_type":"primary","measure":"Diagnostic performance (Negative Predictive Value)","time_frame":"2 weeks","description":"Patient-level negative predictive value to identify residual carcinoma"},{"outcome_type":"secondary","measure":"Orientation-level diagnostic performance","time_frame":"2 weeks","description":"Orientation-level diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of cancer in the surgical cavity after SoC as compared to margin histopathology."},{"outcome_type":"secondary","measure":"Positive margin conversion rate among all patients","time_frame":"2 weeks","description":"Percentage of patients with at least one histopathology-positive margin following SoC who then have ALL histopathology-negative margins following FGR, among all patients imaged."},{"outcome_type":"secondary","measure":"Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC BCS","time_frame":"2 weeks","description":"Patient-level diagnostic performance characteristics of sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC BCS."},{"outcome_type":"secondary","measure":"Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC with modified patient-level definitions","time_frame":"2 weeks","description":"Patient-level diagnostic performance characteristics of sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC (using modified patient-level definitions)."},{"outcome_type":"secondary","measure":"Patient-level false negative rate of at the end of FGR","time_frame":"2 weeks","description":"Percentage of patients assessed as residual tumor negative at the end of FGR who had positive final margins on histopathology"},{"outcome_type":"secondary","measure":"Patient-level false positive rate","time_frame":"2 weeks","description":"Percentage of patients in whom SOC final margins were carcinoma negative and all FL-driven shave specimens are carcinoma-negative"},{"outcome_type":"secondary","measure":"Patients with carcinoma-negative margins after SoC found to have residual tumor following SoC that was identified with FL imaging","time_frame":"2 weeks","description":"Percentage of patients with histopathology-negative margins at the end of SoC who have at least one orientation that was both FL-positive and histopathology-positive among (1) patients with histopathology negative final margins after SOC and (2) all patients imaged"},{"outcome_type":"secondary","measure":"Patient-level true negative rate at the end of SoC","time_frame":"2 weeks","description":"Percentage of patients with no fluorescence identified at the end of SoC in whom all final margins after SoC are histopathologically confirmed to be negative for carcinoma."},{"outcome_type":"secondary","measure":"Patient-level diagnostic performance to identify in vivo residual carcinoma after FGR","time_frame":"2 weeks","description":"Patient-level in vivo diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR as compared to the final margin histopathology."},{"outcome_type":"secondary","measure":"Orientation discordant fluorescence status","time_frame":"2 weeks","description":"Percentage of orientations where in vivo and ex vivo fluorescence assessments are discordant."},{"outcome_type":"secondary","measure":"Patient-level re-operation rate","time_frame":"1 year","description":"Percentage of patients receiving a 2nd surgery on the ipsilateral breast within 1 year of index BCS to remove suspected residual disease."},{"outcome_type":"secondary","measure":"Patient-level early re-operation rate","time_frame":"3 - 6 months","description":"Percentage of patients receiving an early 2nd surgery (planned or actual) on the ipsilateral breast related to positive final margins."},{"outcome_type":"secondary","measure":"Amount of tissue removed with FGR beyond SoC","time_frame":"2 weeks","description":"Weight (mg) of all tissue removed based on SoC and/of FGR"},{"outcome_type":"secondary","measure":"Patient satisfaction with breast","time_frame":"2 weeks, 3-, 6- and 12-months","description":"Patient satisfaction with the cosmetic outcome of breast conserving surgery performed based on SoC in combination with PD G 506 A and the Eagle V1.2 Imaging System"}]}
{"nct_id":"NCT04804254","start_date":"2021-04-27","phase":"Phase 1","enrollment":105,"brief_title":"Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers","official_title":"A Phase 1 First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of ABBV-623 and ABBV-992 in Subjects With B-cell Malignancies","primary_completion_date":"2023-04-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-04-29","last_update":"2021-09-22","description":"B-cell cancer is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The main objective of this study is to evaluate the safety and efficacy of ABBV-623 and ABBV-992 given alone and in combination in treating B-cell cancers. Adverse events, change in disease activity and how the drug moves through the body of adult participants with B-cell cancers will be evaluated. ABBV-623 and ABBV-992 are investigational drugs being developed for the treatment of B-cell cancer. Study doctors assign participants to one of six groups, called treatment arms. Approximately 105 adult participants with a diagnosis of B-cell cancer will be enrolled in the study at approximately 50 sites worldwide. Participants in the combination expansion treatment arms will receive oral tablets of ABBV-623 and/or ABBV-992 once daily for 24 months. All other arms are treated until progression. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be evaluated by medical assessments and blood tests. Adverse events will be collected and assessed throughout the clinical trial.","other_id":"M20-208","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Participants must have documented diagnosis for one of the following B-cell\r\n             malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL),\r\n             Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenstrm's\r\n             macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma\r\n             (FL), with measurable disease requiring treatment.\r\n\r\n          -  Participants have relapsed or refractory to at least 2 prior systemic therapies.\r\n\r\n          -  Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL\r\n             with measurable disease requiring treatment per by International Workshop on Chronic\r\n             Lymphocytic Leukemia (IWCLL) criteria.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1.\r\n\r\n          -  CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure\r\n             will be allowed if participant did not progress on active treatment and there is no\r\n             evidence of resistance mutations.\r\n\r\n          -  Renal, liver and hematological function lab values as determined in the protocol.\r\n\r\n          -  For participants with prior BTK inhibitor exposure, no evidence of mutations which\r\n             confer resistance to covalent BTK inhibitors.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate\r\n             cytoreduction.\r\n\r\n          -  Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except\r\n             for participants in the ABBV-992 monotherapy cohort).\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"B-cell Lymphoma","interventions":[{"intervention_type":"Drug","name":"Drug: ABBV-623","description":"Oral Tablets"},{"intervention_type":"Drug","name":"Drug: ABBV-992","description":"Oral Tablets"}],"outcomes":[{"outcome_type":"primary","measure":"Percentage of Participants With Adverse Events (AEs)","time_frame":"Up to approximately 25 months.","description":"An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above."},{"outcome_type":"primary","measure":"Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623","time_frame":"Up to approximately 96 weeks","description":"The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-623 achieves in the blood after administration in a dosing interval."},{"outcome_type":"primary","measure":"Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623","time_frame":"Up to approximately 96 weeks","description":"The area under the plasma concentration-time curve (AUC; measured in h*ng/mL/mg) is a method of measurement of the total exposure of ABBV-623 in blood plasma."},{"outcome_type":"primary","measure":"Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992","time_frame":"Up to approximately 96 weeks.","description":"The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that ABBV-992 achieves in the blood after administration in a dosing interval."},{"outcome_type":"primary","measure":"Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992","time_frame":"Up to approximately 96 weeks","description":"The area under the plasma concentration-time curve (AUC; measured in h*ng/mL/mg) is a method of measurement of the total exposure of ABBV-992 in blood plasma."},{"outcome_type":"primary","measure":"Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL","time_frame":"Up to approximately 2 years","description":"ORR is the proportion of R/R CLL/SLL participants achieving a response of PR or better per IWCLL without the use of new anti-cancer therapy."},{"outcome_type":"secondary","measure":"Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)","time_frame":"Up to approximately 2 years","description":"Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol."},{"outcome_type":"secondary","measure":"Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better","time_frame":"Up to approximately 2 years","description":"Duration of Response (DOR) is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first."},{"outcome_type":"secondary","measure":"Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)","time_frame":"Up to approximately 2 years","description":"Time to response, defined as the length of time from the date of first dose of study drug to the date of first response of PR or better per disease-specific response criteria."},{"outcome_type":"secondary","measure":"Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better","time_frame":"Up to approximately 2 years","description":"Partial response (PR) as per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) , Lugano, International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria in protocol."},{"outcome_type":"secondary","measure":"Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better","time_frame":"Up to approximately 2 years","description":"Duration of Response (DOR) is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first."},{"outcome_type":"secondary","measure":"Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)","time_frame":"Up to approximately 2 years","description":"Time to response, defined as the length of time from the date of first dose of study drug to the date of first response of PR or better per disease-specific response criteria."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)","time_frame":"Up to approximately 6 months","description":"Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)","time_frame":"Up to approximately 1 Year","description":"Undetectable minimal residual disease (uMRD) is described as less than one myeloma cell per million bone marrow cells."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD","time_frame":"Up to approximately 96 weeks","description":"Peripheral blood Undetectable minimal residual disease (uMRD) is described as less than one CLL cell per 10,000 leukocytes (or below 10^-4) or as specified in the protocol."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better","time_frame":"Up to approximately 2 years","description":"Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Time to Response","time_frame":"Up to approximately 2 years","description":"Time to response is defined by the time between the date of the first drug intake and the date of the first assessment having documented the response."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival","time_frame":"Approximately 2 years after study drug discontinuation","description":"Progression free survival (PFS) is defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first."},{"outcome_type":"secondary","measure":"Combination Dose Expansion in Participants With CLL/SLL: Overall Survival","time_frame":"Approximately 2 years after study drug discontinuation","description":"Overall Survival is defined as the number of days from the date the participant was randomized to the date of death."}]}
{"nct_id":"NCT04784715","start_date":"2021-04-26","phase":"Phase 3","enrollment":1134,"brief_title":"Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)","official_title":"Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)","primary_completion_date":"2025-07-24","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2029-12-30","last_update":"2021-09-01","description":"The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment.","other_id":"D967UC00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Study will consist of three arms:\r\nArm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Patients must be 18 years of age\r\n\r\n          -  Pathologically documented breast cancer that:\r\n\r\n               1. is advanced or metastatic\r\n\r\n               2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+\r\n                  or ISH+)\r\n\r\n               3. is documented by local testing as hormone receptor (HR)-positive or HR-negative\r\n                  disease in the metastatic setting\r\n\r\n          -  No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast\r\n             cancer or only 1 previous line of endocrine therapy in the metastatic setting.\r\n             Participants who have received chemotherapy or HER2-targeted therapy in the\r\n             neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to\r\n             metastatic diagnosis.\r\n\r\n          -  Has protocol-defined adequate organ and bone marrow function\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Ineligible for any of the agents on the study.\r\n\r\n          -  Any substance abuse or other medical conditions that, in the investigator's opinion,\r\n             may interfere with subject's participation or study results\r\n\r\n          -  Patients with spinal cord compression or clinically active central nervous system\r\n             metastases. Participants with clinically inactive brain metastases or treated brain\r\n             metastases that are no longer symptomatic may be included in the study.\r\n\r\n          -  Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected\r\n             ILD/pneumonitis that cannot be ruled out by imaging at screening\r\n\r\n          -  Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless\r\n             of treatment arm assignment\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Breast Cancer; HER2-positive; Metastatic","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab deruxtecan","description":"Administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Taxane","description":"Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Pertuzumab","description":"Administered by intravenous infusion"},{"intervention_type":"Drug","name":"Drug: Trastuzumab","description":"Administered by intravenous infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment","time_frame":"Until progression or death, assessed up to approximately 60 months","description":"Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) by Investigator assessment","time_frame":"Until progression or death, assessed up to approximately 60 months","description":"Defined as time from date of randomisation until the date of objective radiological disease progression according to Investigator using RECIST 1.1 or death by any cause."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Until death, assessed up to approximately 104 months","description":"OS is defined as the time from randomisation until the date of death due to any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by BICR and Investigator assessment","time_frame":"Until progression or death (in the absence of progression), assessed up to approximately 60 months","description":"ORR is defined as The percentage of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DoR) by BICR and Investigator Assessment","time_frame":"Until progression or death (in the absence of progression), assessed up to approximately 60 months","description":"DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression."},{"outcome_type":"secondary","measure":"Time to second progression or death (PFS2) by Investigator assessment","time_frame":"Assessed up to approximately 104 months","description":"PFS2 is defined as the time from randomisation until the date of tumor progression on next-line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy after the first progression) or death from any cause (after death from any cause); second progression will be defined according to local standard clinical practice."},{"outcome_type":"secondary","measure":"Health related quality of life (HRQoL) using the EORTC QLQ-C30","time_frame":"Assessed up to approximately 60 months","description":"Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30"},{"outcome_type":"secondary","measure":"Time to deterioration in EORTC-QLQ-C30 scores","time_frame":"Assessed up to approximately 60 months","description":"Time to deterioration in EORTC QLQ C30 physical and role function, global health status/QoL and pain scores."},{"outcome_type":"secondary","measure":"Health related quality of life (HRQoL) using the EORTC QLQ-BR45","time_frame":"Assessed up to approximately 60 months","description":"Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BR45"},{"outcome_type":"secondary","measure":"Serum concentration of trastuzumab deruxtecan and pertuzumab","time_frame":"Up to Cycle 8, approximately Week 24; each cycle is 21 days","description":"Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum."},{"outcome_type":"secondary","measure":"Immunogenicity of trastuzumab deruxtecan, alone or with pertuzumab.","time_frame":"Up to follow-up period, approximately 60 months","description":"Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan.\r\nNumber and percentage of participants who develop ADA for pertuzumab"},{"outcome_type":"secondary","measure":"Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab","time_frame":"Assessed up to approximately 60 months","description":"Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm"}]}
{"nct_id":"NCT04770896","start_date":"2021-04-26","phase":"Phase 3","enrollment":554,"brief_title":"A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab","official_title":"A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab","primary_completion_date":"2024-10-08","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-10-08","last_update":"2021-08-27","description":"This is a Phase III, open label, randomized, two-arm, multicenter study designed to evaluate the safety and efficacy of atezolizumab plus lenvatinib or sorafenib versus lenvatinib or sorafenib alone in locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) participants who have progressed following prior HCC treatment with atezolizumab and bevacizumab combination.","other_id":"MO42541","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by\r\n             histology/ cytology or clinically by American Association for the Study of Liver\r\n             Diseases (AASLD) criteria in cirrhotic patients.\r\n\r\n          -  Disease progression following prior atezolizumab plus bevacizumab combination\r\n             treatment for HCC, for at least 4 consecutive treatment cycles, or 2 subsequent tumor\r\n             assessments, whichever is longer.\r\n\r\n          -  At least one measurable (per RECIST v1.1) target lesion that has not been previously\r\n             treated with local therapy or, if the target lesion is within the field of previous\r\n             local therapy, has subsequently progressed in accordance with RECIST v1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7\r\n             days prior to randomization\r\n\r\n          -  Child-Pugh class A within 7 days prior to randomization\r\n\r\n          -  Adequate hematologic and end-organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)\r\n             metastases.\r\n\r\n          -  History of leptomeningeal disease\r\n\r\n          -  History of hepatic encephalopathy, proceeding 6 months, unresponsive to therapy within\r\n             3 days\r\n\r\n          -  Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC\r\n\r\n          -  History of malignancy other than HCC within 5 years prior to screening, with the\r\n             exception of malignancies with a negligible risk of metastasis or death\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Unresectable Hepatocellular Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator."},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of < 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of  60 kg will receive a daily dose of 12 mg."},{"intervention_type":"Drug","name":"Drug: Sorafenib","description":"Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Randomization until death from any cause (approximately 42 months)","description":"Overall survival (OS) is defined as the time from randomization into the study to death from any cause."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS)","time_frame":"Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)","description":"Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"Approximately 42 months","description":"Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response."},{"outcome_type":"secondary","measure":"Time to Progression (TTP)","time_frame":"Randomization until the first occurrence of disease progression (approximately 42 months)","description":"Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months)","description":"Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"Time to deterioration (TTD)","time_frame":"Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months)","description":"Time to deterioration (TTD) is defined as the time from randomization to first deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30(EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL."},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events","time_frame":"Throughout study duration (approximately 42 months)"},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events","time_frame":"Throughtout study (approximately 42 months)"},{"outcome_type":"secondary","measure":"Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab","time_frame":"Throughout study (approximately 42 months)"},{"outcome_type":"secondary","measure":"Serum Concentration of Atezolizumab","time_frame":"At pre-defined intervals from first administration of study drug to approximately 42 months"}]}
{"nct_id":"NCT04659629","start_date":"2021-04-26","phase":"Phase 1","enrollment":120,"brief_title":"NL-201 in Patients With Relapsed or Refractory Cancer","official_title":"A First-in-Human Phase 1 Study of NL-201 in Patients With Relapsed or Refractory Cancer","primary_completion_date":"2023-05-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-08-30","description":"The primary purpose of this study is to understand the safety of NL-201 when given intravenously as monotherapy in patients with advanced cancer to evaluate tolerability and to identify a recommended dose and schedule for further testing.","other_id":"NL201-101","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients with measurable disease\r\n\r\n          -  Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  At least 6 weeks from any prior nitrosurea or mitomycin C therapy; at least 4 weeks\r\n             from any other prior chemotherapy or checkpoint inhibitor; at least 2 weeks from any\r\n             kinase inhibitor\r\n\r\n          -  Patients with relapsed or refractory advanced solid tumor, other than prostate cancer,\r\n             who have progressed, not tolerated or are ineligible for all approved lines of therapy\r\n\r\n          -  Part 2 Only: Patients with kidney and skin cancer who have failed at least 1 line of\r\n             systemic therapy\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prostate Cancer\r\n\r\n          -  Any serious medical condition or laboratory abnormality or psychiatric condition or\r\n             any other significant or unstable concurrent medical illness (in the opinion of the\r\n             Investigator) would preclude protocol adherence or would make the safety of the study\r\n             drug difficult to assess\r\n\r\n          -  Known or suspected SARS-CoV-2 infection, unless patient tests negative for SARS-CoV-2\r\n             within the Screening period\r\n\r\n          -  History of solid organ transplant or bone marrow transplant\r\n\r\n          -  Prior CAR-T or allogeneic cellular therapy\r\n\r\n          -  Prior IL-2-based cancer therapy\r\n\r\n          -  Ongoing systemic immunosuppressive therapy\r\n\r\n          -  Concurrent therapy with any other investigational agent, vaccine, or device.\r\n      ","sponsor":"Neoleukin Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Solid Tumor|Advanced Solid Tumor","interventions":[{"intervention_type":"Drug","name":"Drug: NL-201","description":"NL-201 is a de novo protein therapeutic."}],"outcomes":[{"outcome_type":"other","measure":"Serum measurements of inflammatory cytokine levels","time_frame":"Up to 36 months","description":"Based on appropriate assay"},{"outcome_type":"other","measure":"Analysis of immune characteristics of the tumor microenvironment","time_frame":"Up to 36 months","description":"Based on appropriate assay"},{"outcome_type":"other","measure":"Estimate additional measures of anti-tumor activity of NL- 201 per iRECIST criteria","time_frame":"Up to 36 months","description":"Based on Investigator assessment of imaging"},{"outcome_type":"primary","measure":"Recommended phase 2 dose (RP2D) for NL-201","time_frame":"Up to Day 33","description":"Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)"},{"outcome_type":"primary","measure":"Recommended dose schedule for NL-201","time_frame":"Up to Day 33","description":"Evaluation of tolerability of NL-201 as measured by number of subjects with dose limiting toxicities (DLTs)"},{"outcome_type":"primary","measure":"Incidence of treatment-emergent adverse events","time_frame":"Up to Day 33","description":"Rate of adverse events in patients with advanced solid tumors"},{"outcome_type":"primary","measure":"Severity of treatment-emergent adverse events","time_frame":"Up to Day 33","description":"Rate of adverse event grades in patients with advanced solid tumors"},{"outcome_type":"secondary","measure":"Best Objective Response according to RECIST version 1.1","time_frame":"Up to 36 months","description":"Based on Investigator assessment of radiographic imaging"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) according to RECIST version 1.1","time_frame":"Up to 36 months","description":"Based on Investigator assessment of radiographic imaging"},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) according to RECIST version 1.1","time_frame":"Up to 36 months","description":"Based on Investigator assessment of radiographic imaging"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) according to RECIST version 1.1","time_frame":"Upto 36 months","description":"Based on Investigator assessment of radiographic imaging"},{"outcome_type":"secondary","measure":"Pharmacokinetic (PK) profile of NL-201 by half-life (t1/2)","time_frame":"Up to 24 Months","description":"Prespecified timepoints in serum before and after dosing with NL-201."},{"outcome_type":"secondary","measure":"Pharmacokinetic (PK) profile of NL-201 by area under the plasma concentration time curve (AUC)","time_frame":"Up to 24 months","description":"Prespecified timepoints in serum before and after dosing with NL-201."},{"outcome_type":"secondary","measure":"Pharmacokinetic (PK) profile of NL-201 by maximum observed plasma concentration (Cmax)","time_frame":"Up to 24 months","description":"Prespecified timepoints in serum before and after dosing with NL-201."},{"outcome_type":"secondary","measure":"Pharmacokinetic (PK) profile of NL-201 by volume of distribution (Vd)","time_frame":"Up to 24 Months","description":"Prespecified timepoints in serum before and after dosing with NL-201."},{"outcome_type":"secondary","measure":"Immunogenicity of NL-201","time_frame":"Up to 24 months","description":"Anti-drug antibodies in serum during and after treatment with NL-201"},{"outcome_type":"other","measure":"Flow cytometry analysis of immune cells in blood","time_frame":"Up to 36 months","description":"Based on appropriate assay"}]}
{"nct_id":"NCT04868162","start_date":"2021-04-23","phase":"Phase 2","enrollment":120,"brief_title":"A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck","official_title":"An Open-Label, Single Arm, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck.","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-09-30","last_update":"2021-04-30","description":"The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in patients with recurrent or metastatic squamous cell carcinoma of head and neck.","other_id":"MRG003-004","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Willing to sign the ICF and follow the requirements specified in the protocol.\r\n\r\n          -  Age: 18 years, both genders.\r\n\r\n          -  Expected survival time3 months.\r\n\r\n          -  Patients with histologically confirmed unresectable recurrent or metastatic squamous\r\n             cell carcinoma of head and neck.\r\n\r\n          -  Failed in the prior platinum and/or anti-PD-1 treatment.\r\n\r\n          -  Patients must have measurable lesions according to the Response Evaluation Criteria in\r\n             Solid Tumors (RECIST v1.1).\r\n\r\n          -  ECOG performance score 0 or 1.\r\n\r\n          -  Organ functions and coagulation function must meet the basic requirements.\r\n\r\n          -  No severe cardiac dysfunction with left ventricular ejection fraction (LVEF)  50%.\r\n\r\n          -  Serum or urine pregnancy test negative within 7 days before the first dose of\r\n             investigational drug.\r\n\r\n          -  Patients with childbearing potential must use effective contraception during the\r\n             treatment and for 6 months after the last dose of treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History of 4 or more systemic anti-tumor therapies for the recurrent or metastatic\r\n             squamous cell carcinoma of head and neck.\r\n\r\n          -  Expected surgery or any other form of systemic or local anti-tumor therapy.\r\n\r\n          -  History of systemic chemotherapy within 3 weeks before the first administration of the\r\n             investigational drug, targeted small molecule therapy within 2 weeks or 5 half-life\r\n             periods before the first administration (whichever is shorter), antitumor biological\r\n             therapy or immunotherapy within 4 weeks before the first administration, or major\r\n             surgery.\r\n\r\n          -  Known active CNS metastasis and/or cancerous meningitis.\r\n\r\n          -  Residual toxicity reactions caused by previous anti-tumor treatment or abnormal values\r\n             of laboratory tests higher than grade 1 (CTCAE v5.0).\r\n\r\n          -  Uncontrolled or poorly controlled heart disease.\r\n\r\n          -  History of pulmonary embolism or deep vein thrombosis within 3 months before the first\r\n             administration of the investigational drug.\r\n\r\n          -  Known history of malignancy.\r\n\r\n          -  Uncontrolled or poorly controlled hypertension.\r\n\r\n          -  Patients with a history of active bleeding, coagulopathy, or receiving coumarin\r\n             anticoagulation therapy.\r\n\r\n          -  Known allergic reaction to any ingredients or excipients of MRG003.\r\n\r\n          -  Known active hepatitis B or C.\r\n\r\n          -  Complicated with severe, uncontrolled infection or known human immunodeficiency virus\r\n             (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or\r\n             uncontrolled autoimmune disease; or history of allogeneic tissue/organ\r\n             transplantation, stem cell or bone marrow transplantation, or solid organ\r\n             transplantation.\r\n\r\n          -  Active bacterial, viral, fungal, rickettsia, or parasitic infections that require\r\n             systemic anti-infective treatment.\r\n\r\n          -  Vaccination of live virus vaccine within 30 days before the first administration of\r\n             the study drug. Inactivated seasonal influenza vaccine or approved COVID-19 vaccine is\r\n             allowed.\r\n\r\n          -  Moderate to severe dyspnea at rest caused by advanced cancer or its complications, or\r\n             severe primary lung disease, oxygen saturation < 93% in non-oxygen state, or history\r\n             of any interstitial lung disease or interstitial lung disease (ILD) requiring oral or\r\n             intravenous glucocorticoids or non-infectious pneumonia.\r\n\r\n          -  Patients receiving immunology-based treatment for any reason.\r\n\r\n          -  Uncontrolled pleural effusion, pericardial effusion or recurrent ascites.\r\n\r\n          -  Potent CYP3A4 inhibitors or inducers are in use and cannot be discontinued.\r\n\r\n          -  Women who are lactating or pregnant.\r\n\r\n          -  Other conditions that in the clinical judgement of the investigator make the patient\r\n             not suitable for participation in this study.\r\n      ","sponsor":"Shanghai Miracogen Inc.","sponsor_type":"Industry","conditions":"Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck","interventions":[{"intervention_type":"Drug","name":"Drug: MRG003","description":"Administered intravenously"}],"outcomes":[{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by Investigator","time_frame":"Baseline to study completion (up to 24 months)","description":"ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) by Independent Review Committee (IRC)","time_frame":"Baseline to study completion (up to 24 months)","description":"ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by Independent Review Committee (IRC) according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) and Progression Free Survival Rate (PFSR)","time_frame":"Baseline to study completion (up to 24 months)","description":"PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Baseline to study completion (up to 24 months)","description":"DOR is defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Baseline to study completion (up to 24 months)","description":"DCR is defined as the proportions of patients achieving CR, PR, and stable disease (SD) after treatment."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Baseline to study completion (up to 24 months)","description":"OS is defined as the duration from the start of treatment to death of any cause."},{"outcome_type":"secondary","measure":"Adverse Events (AEs)","time_frame":"Baseline to 45 days after the last dose of study treatment","description":"Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug."},{"outcome_type":"secondary","measure":"PK parameter for MRG003: Maximum Drug Concentration (Cmax)","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Maximum observed plasma concentration."},{"outcome_type":"secondary","measure":"PK parameter for MRG003: (AUClast)","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Area under the curve up to the last validated measurable plasma concentration"},{"outcome_type":"secondary","measure":"PK parameter for total antibody (TAb): Cmax","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Maximum observed plasma concentration."},{"outcome_type":"secondary","measure":"PK parameter for TAb: AUClast","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Area under the curve up to the last validated measurable plasma concentration"},{"outcome_type":"secondary","measure":"PK parameter for Monomethyl Auristatin E (MMAE): Cmax","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Maximum observed plasma concentration."},{"outcome_type":"secondary","measure":"PK parameter for MMAE: AUClast","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"Area under the curve up to the last validated measurable plasma concentration"},{"outcome_type":"secondary","measure":"Incidence of anti-drug antibody (ADA)","time_frame":"Baseline to 30 days after the last dose of study treatment","description":"The proportion of patients with positive ADA immunogenicity results."}]}
{"nct_id":"NCT04818333","start_date":"2021-04-23","phase":"Phase 1/Phase 2","enrollment":120,"brief_title":"A Study of SHR-A1811 in Subjects With Advanced Non-small Cell Lung Cancer","official_title":"Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of SHR-A1811 for Injection in Subjects With Advanced Non-small Cell Lung Cancer Who Have HER2 Expression , Amplification, or Mutation","primary_completion_date":"2023-01-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-30","last_update":"2021-06-04","description":"This is an open-label, two-part study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SHR-A1811 for injection in subjects with advanced non-small cell lung cancer who have HER2 expression , amplification, or mutation","other_id":"SHR-A1811-I-103","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Single arm study of SHR-A1811","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Able and willing to provide a written informed consent\r\n\r\n          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          3. advanced non-small cell lung cancer with HER2 expression , amplification, or mutation\r\n\r\n          4. has previously received platinum-based chemotherapy for advanced or metastatic NSCLC,\r\n             has developed disease progression during or after treatment, or is unable to tolerate\r\n             platinum-based chemotherapy.\r\n\r\n          5. There is at least one measurable lesion according to RECIST V1.1 criteria\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has unresolved toxicities from previous anticancer therapy, defined as toxicities not\r\n             yet resolved to NCI-CTCAE version 5.0 grade  1.\r\n\r\n          2. Has received HER2 antibody drug conjugates,\r\n\r\n          3. Central nervous system metastasis or meningeal metastasis with clinical symptoms\r\n\r\n          4. Has active infection requiring systemic treatment.\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SHR-A1811","description":"Phase 1 Drug: SHR-A1811 There are four pre-defined dose regimens . Subjects will be enrolled with an initial dose Phase 2 Drug: SHR-A1811 Doses will be determined from Phase 1"}],"outcomes":[{"outcome_type":"primary","measure":"Phase 1: Recommended Phase 2 dose (RP2D)","time_frame":"12 months","description":"RP2D was determined based on the safety, tolerability, PK, immunogenicity data and efficacy information obtained"},{"outcome_type":"primary","measure":"Phase 1:Incidence of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811","time_frame":"From Day 1 to90 days after last dose ，appropriately to 3 years","description":"Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0)"},{"outcome_type":"primary","measure":"Phase 1:Severity of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811","time_frame":"From Day 1 to90 days after last dose ，appropriately to 3 years","description":"Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0)"},{"outcome_type":"primary","measure":"Phase1: Maximum tolerated dose (MTD)","time_frame":"12 months","description":"Incidence rate and category of dose limiting toxicities (DLTs) during the first 21-day cycle of SHR-A1811 treatment"},{"outcome_type":"primary","measure":"Phase2:ObjectiveResponse Rate (ORR)","time_frame":"Subjects were evaluated on tumor imaging every 6 weeks after treatment initiation and every 12 weeks after 54 weeks, until imaging progression, initiation of new antitumor therapy, loss of follow-up, and death，appropriately to 3 years","description":"As assessed by RECIST v1.1 , as assessed by independent review committee (IRC)"},{"outcome_type":"secondary","measure":"Phase 1：PK parameter ：Tmax of SHRA1811","time_frame":"appropriately to 3 years","description":"Time to maximal concentration (Tmax) of SHR-A1811"},{"outcome_type":"secondary","measure":"Phase1:PK parameter: Cmax of SHR-A1811","time_frame":"appropriately to 3 years","description":"Maximal concentration (Cmax) of SHR-A1811"},{"outcome_type":"secondary","measure":"Phase1:PK parameter: AUC0-t of SHR-A1811","time_frame":"appropriately to 3 years","description":"AUC computed from time zero to the time of the last quantifiable concentration (AUC0-t) of SHR-A1811"},{"outcome_type":"secondary","measure":"Phase1:Immunogenicity of SHR-A1811","time_frame":"Immunogenicity sample collection time points include: within 30 min before administration of C1D1, C2D1, C3D1, C4D1, C6D1 and C8D1 starting from cycle 11 only in every 3 cycles ,appropriately to 3 years","description":"Including anti-drug antibody and/or neutralizing antibody"},{"outcome_type":"secondary","measure":"Phase2:Progression Free Survival (PFS)","time_frame":"appropriately to 3 years","description":"As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator"},{"outcome_type":"secondary","measure":"Phase2:ObjectiveResponse Rate (ORR)","time_frame":"appropriately to 3 years","description":"As assessed by RECIST v1.1 , as assessed by investigator"},{"outcome_type":"secondary","measure":"Phase2:Duration of response (DOR)","time_frame":"appropriately to 3 years","description":"As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator"},{"outcome_type":"secondary","measure":"Phase2:Disease control rate (DCR)","time_frame":"appropriately to 3 years","description":"As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator"},{"outcome_type":"secondary","measure":"Phase2:Overall survival (OS)","time_frame":"Approximately 5 years after last subject enrolled"}]}
{"nct_id":"NCT04729608","start_date":"2021-04-22","phase":"Phase 3","enrollment":500,"brief_title":"Study of AVB-S6-500 in Combination With Paclitaxel vs Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer","official_title":"A Phase 3, Randomized, Double-Blind, Adaptive, Placebo/Paclitaxel-Controlled Study of AVB-S6-500 in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer","primary_completion_date":"2023-07-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-07-31","last_update":"2021-08-18","description":"This is a Phase 3 study of AVB-S6-500 in combination with paclitaxel (Pac) in patients with platinum resistant recurrent ovarian cancer. This is a randomized, double-blind, placebo-controlled study to compare efficacy and tolerability of AVB-S6-500 in combination with Pac versus placebo plus Pac.","other_id":"AVB500-OC-004","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed and documented recurrent ovarian, fallopian tube, or\r\n             peritoneal cancer. Only patients with high-grade serous adenocarcinoma histology are\r\n             eligible.\r\n\r\n          -  Aged 18 years or older\r\n\r\n          -  Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1\r\n\r\n          -  Platinum-resistant disease (defined as progression within 6 months from completion of\r\n             most recent platinum-containing regimen and calculated from the date of the last\r\n             administered dose of platinum therapy).\r\n\r\n          -  Available archived tumor tissue or if archived tissue is not available, a fresh tumor\r\n             biopsy.\r\n\r\n          -  Received at least 1 but not more than 4 prior therapy regimens. Note: maintenance\r\n             therapy OR hormonal therapies should not be counted as a separate therapy.\r\n\r\n          -  Measurable disease according to RECIST v1.1 criteria\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Tumors in the breast or bone\r\n\r\n          -  Untreated central nervous system (CNS) metastases (surgery and/or radiotherapy).\r\n             Subjects requiring corticosteroid therapy for the management of their treated CNS\r\n             metastases may not be on >10 mg/day prednisone or equivalent or have demonstrated\r\n             signs or symptoms of neurologic instability for 28 days or less prior to\r\n             randomization.\r\n\r\n          -  Primary platinum-refractory disease (defined as progression during or within 4 weeks\r\n             after completion of the first platinum regimen)\r\n\r\n          -  Is being treated with concurrent anticancer therapy or other interventional treatments\r\n             administered for their underlying ovarian cancer.\r\n\r\n          -  Received prior therapy with PAC in the recurrent setting\r\n      ","sponsor":"Aravive, Inc.","sponsor_type":"Industry","conditions":"Platinum-resistant Ovarian Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AVB-S6-500","description":"AVB-S6-500 is an experimental drug"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Paclitaxel is the standard of care, background therapy"},{"intervention_type":"Other","name":"Other: Placebo","description":"Matching placebo"}],"outcomes":[{"outcome_type":"primary","measure":"Anti-tumor activity of AVB-S6-500 in combination with Pac measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac","time_frame":"4 months","description":"PFS is the time interval between randomization and radiologically documented disease progression or death, whichever comes first."},{"outcome_type":"secondary","measure":"Overall survival","time_frame":"20 months","description":"Time following the treatment until death"},{"outcome_type":"secondary","measure":"Objective response rate (ORR)","time_frame":"3 months","description":"Proportion of subjects who have a confirmed partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"9 months","description":"Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria."},{"outcome_type":"secondary","measure":"Incidence of Treatment Emergent Adverse Events (TEAEs)","time_frame":"10 months"},{"outcome_type":"secondary","measure":"Quality of Life (QOL)","time_frame":"10 months","description":"Subject QOL will be assessed using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 \"not at all\" and 4 \"very much\". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items)."},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR)","time_frame":"4 months"},{"outcome_type":"secondary","measure":"Area under the AVB-S6-500 concentration-time curve.","time_frame":"10 months"},{"outcome_type":"secondary","measure":"Maximum observed AVB-S6-500 concentration.","time_frame":"10 months"},{"outcome_type":"secondary","measure":"Time of maximum observed AVB-S6-500 concentration.","time_frame":"10 months"},{"outcome_type":"secondary","measure":"Half-life of AVB-S6-500.","time_frame":"10 months"},{"outcome_type":"secondary","measure":"Pharmacodynamic marker assessment","time_frame":"10 months","description":"Change from the baseline in GAS6 serum levels."},{"outcome_type":"secondary","measure":"Anti-drug antibody (ADA) titers","time_frame":"10 months"}]}
{"nct_id":"NCT04835714","start_date":"2021-04-20","phase":"Phase 1","enrollment":124,"brief_title":"A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS])","official_title":"A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With BI 3011441 in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours","primary_completion_date":"2023-10-17","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-07-07","last_update":"2021-09-08","description":"This is a study in adults with advanced cancer (solid tumours including non-small cell lung cancer and colorectal cancer) in whom previous chemotherapy was not successful. People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster. The study tests 2 medicines called BI 1701963 and BI 3011441. BI 1701963 and BI 3011441 prevent activation of KRAS. The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with BI 3011441 the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with BI 3011441 is able to make tumours shrink. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, they get tablets of BI 1701963 and capsules of BI 3011441 once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.","other_id":"1432-0006","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS)\r\n             mutation in tumour tissue or blood prior to screening. Activating mutations may\r\n             include but are not limited to: KRAS mutations in expressed region (exon) 2 (G12,\r\n             G13), exon 3 (A59, Q61) and exon 4 (K117, A146).\r\n\r\n          -  Provision of archival tumour tissue, if available, to confirm retrospectively KRAS\r\n             mutation status and for biomarker assessment\r\n\r\n          -  At least one target lesion that can be measured per Response Evaluation Criteria In\r\n             Solid Tumours (RECIST) version 1.1. In patients who only have one target lesion, and a\r\n             biopsy of the lesion is required, the baseline imaging must be performed at the\r\n             earliest two weeks after the biopsy.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening\r\n\r\n          -  Adequate organ function at screening as follows:\r\n\r\n               -  Absolute neutrophil count (ANC) 1.5 x 109/L; hemoglobin 9.0 g/dL; platelets\r\n                  100 x 109/L without the use of haematopoietic growth factors or recent\r\n                  transfusion\r\n\r\n               -  Total bilirubin 1.5 times the upper limit of normal (ULN), or 4 x ULN for\r\n                  patients who are known to have Gilbert's syndrome.\r\n\r\n               -  Creatinine 1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if\r\n                  concurrent glomerular filtration rate (GFR) 50 mL/min (measured or calculated by\r\n                  Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula).\r\n\r\n               -  Aspartate transaminase (AST) and alanine transaminase (ALT) 3 x ULN if no\r\n                  demonstrable liver metastases, or  5 x ULN if transaminase elevation is\r\n                  attributable to liver metastases.\r\n\r\n          -  Age 18 years of age, or over the legal age of consent as required by local\r\n             legislation at informed consent.\r\n\r\n          -  Recovery from any previous therapy related toxicity to Common Terminology Criteria for\r\n             Adverse Events (CTCAE) Grade 1 at Cycle 1 Day 1 (except for alopecia, stable sensory\r\n             neuropathy must be CTCAE Grade 2 and except for amenorrhea/menstruation related\r\n             disorders of any grade) before the first dose.\r\n\r\n          -  Signed and dated written informed consent in accordance with Good Clinical Practice\r\n             (GCP) and local legislation prior to admission to the trial.\r\n\r\n        Further inclusion criteria apply.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Previous anticancer chemotherapy or anticancer immunotherapy within 3 weeks of the\r\n             first administration of trial drug. Previous anticancer hormonal treatment within 2\r\n             weeks of the first administration of trial drugs.\r\n\r\n          -  Previous treatment with Rat sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or\r\n             Son of Sevenless 1 (SOS1) targeting agents\r\n\r\n          -  Radiotherapy within 4 weeks prior to start of treatment except as follows\r\n\r\n               -  Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks\r\n                  prior to start of treatment\r\n\r\n               -  Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks\r\n                  prior to start of treatment may be allowed but must be discussed with the\r\n                  sponsor.\r\n\r\n          -  Major surgery (major according to the investigator's assessment) performed within 4\r\n             weeks prior to start of treatment or planned during the projected course of the trial,\r\n             e.g. hip replacement.\r\n\r\n          -  Previous treatment with any investigational agent(s) or targeted treatment within 28\r\n             days prior to start of treatment.\r\n\r\n          -  Known history of hypersensitivity to any of the excipients of BI 1701963 tablets\r\n\r\n          -  History or presence of cardiovascular abnormalities such as uncontrolled hypertension,\r\n             congestive heart failure New-York-Heart-Assocation (NYHA) classification of 3,\r\n             unstable angina or poorly controlled arrhythmia which are considered clinically\r\n             relevant by the investigator; myocardial infarction within 6 months prior to start of\r\n             treatment. Uncontrolled hypertension is defined as: Blood pressure (BP) measured in a\r\n             rested and relaxed condition, where systolic BP 140 mmHg, or diastolic BP 90 mmHg,\r\n             with or without medication.\r\n\r\n          -  Left ventricular ejection fraction (LVEF) <50 %. Further exclusion criteria apply.\r\n      ","sponsor":"Boehringer Ingelheim","sponsor_type":"Industry","conditions":"Solid Tumors, KRAS Mutation","interventions":[{"intervention_type":"Drug","name":"Drug: BI 1701963","description":"BI 1701963"},{"intervention_type":"Drug","name":"Drug: BI 3011441","description":"BI 3011441"}],"outcomes":[{"outcome_type":"primary","measure":"Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in monotherapy (Part A)","time_frame":"Up to 28 days"},{"outcome_type":"primary","measure":"Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in combination therapy (Part B)","time_frame":"Up to 28 days"},{"outcome_type":"primary","measure":"Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose confirmation (Part C).","time_frame":"Up to 12 months","description":"Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent."},{"outcome_type":"primary","measure":"Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose expansion (Part D).","time_frame":"Up to 12 months","description":"Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent."},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in monotherapy (Part A)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy (Part B)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in monotherapy (Part A)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy (Part B)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in monotherapy (Part A)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy (Part B)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in monotherapy (Part A)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy (Part B)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 3011441 after the first dose (Part B only)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose (Part B only)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses (Part B only)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses (Part B only)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 months"},{"outcome_type":"secondary","measure":"Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose expansion (Part D)","time_frame":"Up to 12 months"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)","time_frame":"Up to 24 hours"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)","time_frame":"Up to 12 weeks"},{"outcome_type":"secondary","measure":"Duration of Objective Response (OR) in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 months","description":"Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR."},{"outcome_type":"secondary","measure":"Duration of Objective Response (OR) in combination therapy dose expansion (Part D)","time_frame":"Up to 12 months","description":"Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR."},{"outcome_type":"secondary","measure":"Tumour shrinkage (in millimetres) in combination therapy dose confirmation (Part C)","time_frame":"Up to 12 months","description":"Tumour shrinkage (in millimetres) is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions."},{"outcome_type":"secondary","measure":"Tumour shrinkage (in millimetres) in combination therapy dose expansion (Part D)","time_frame":"Up to 12 months","description":"Tumour shrinkage (in millimetres) is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) rate at 6 months in combination therapy dose confirmation (Part C)","time_frame":"Up to 6 months","description":"Based on PFS defined as the time from first administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) rate at 6 months in combination therapy dose expansion (Part D)","time_frame":"Up to 6 months","description":"Based on PFS defined as the time from first administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier"}]}
{"nct_id":"NCT04725188","start_date":"2021-04-20","phase":"Phase 2","enrollment":240,"brief_title":"Pembrolizumab/Vibostolimab Coformulation (MK-7684A) or Pembrolizumab/Vibostolimab Coformulation Plus Docetaxel Versus Docetaxel for Metastatic Non Small Cell Lung Cancer (NSCLC) With Progressive Disease After Platinum Doublet Chemotherapy and Immunotherapy (MK-7684A-002)","official_title":"A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Treatment With a Platinum Doublet Chemotherapy and Immunotherapy","primary_completion_date":"2023-05-17","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-08-13","last_update":"2021-09-20","description":"The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation to normal saline placebo plus docetaxel. Participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) monoclonal antibody (mAb). MK-7684A is a coformulation product of pembrolizumab/vibostolimab. The dual primary hypotheses of the study are pembrolizumab/vibostolimab coformulation plus docetaxel and pembrolizumab/vibostolimab coformulation is superior to normal saline placebo plus docetaxel with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).","other_id":"7684A-002","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell\r\n             lung cancer (NSCLC)\r\n\r\n          -  Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma\r\n             kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as\r\n             primary therapy\r\n\r\n          -  Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1\r\n             (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered\r\n             either as monotherapy or in combination with other checkpoint inhibitors or other\r\n             therapies\r\n\r\n               -  Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall\r\n                  course of treatment\r\n\r\n          -  Has PD as determined by the investigator after platinum doublet chemotherapy for\r\n             metastatic disease\r\n\r\n          -  Has measurable disease defined as at least 1 measurable lesion by computed tomography\r\n             (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in\r\n             Solid Tumors Version 1.1 (RECIST 1.1)\r\n\r\n          -  Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or\r\n             newly obtained core or excisional biopsy of a tumor lesion not previously irradiated\r\n\r\n          -  Has a life expectancy of at least 3 months\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed\r\n             within 7 days prior to randomization\r\n\r\n          -  Male participants randomized to docetaxel are eligible to participant if they agree to\r\n             refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse;\r\n             or 2) must agree to follow contraceptive guidance as per study protocol unless\r\n             confirmed to be azoospermic during the intervention period and for at least 180 days\r\n             after the last dose of docetaxel\r\n\r\n          -  Female participants must be not pregnant, not breastfeeding, and not be a woman of\r\n             child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use\r\n             contraception, or be abstinent from heterosexual intercourse during the intervention\r\n             period and for 120 days after the last dose of study intervention. If a WOCBP is\r\n             randomized to docetaxel, she agrees not to donate eggs and either uses contraception\r\n             or be abstinent from heterosexual intercourse during the treatment period and for 180\r\n             days after the last dose of docetaxel\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has known active or untreated central nervous system (CNS) metastases and/or\r\n             carcinomatous meningitis\r\n\r\n          -  Has a known history of an additional malignancy, except if the participant has\r\n             undergone potentially curative therapy with no evidence of that disease recurrence for\r\n             at least 3 years since initiation of that therapy\r\n\r\n          -  Has received docetaxel as monotherapy or in combination with other therapies\r\n\r\n          -  Has received previous treatment with another agent targeting the T-cell immunoreceptor\r\n             with immunoglobulin [Ig] and immunoreceptor tyrosine-based inhibitory motif [ITIM]\r\n             domains (TIGIT) pathway\r\n\r\n          -  Has received radiotherapy within 2 weeks of start of study intervention. One week\r\n             washout is permitted for palliative radiation to non-CNS disease\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study intervention\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks before the first dose of\r\n             study intervention\r\n\r\n          -  Has severe hypersensitivity (Grade 3) to docetaxel or pembrolizumab/vibostolimab\r\n             coformulation and/or any of its excipients Has an active autoimmune disease that has\r\n             required systemic treatment in past 2 years\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             or any other form of immunosuppressive therapy within 7 days before the first dose of\r\n             study intervention\r\n\r\n          -  Has interstitial lung disease, or history of pneumonitis requiring steroids for\r\n             treatment\r\n\r\n          -  Has known history of active human immunodeficiency virus (HIV), Hepatitis B or\r\n             Hepatitis C\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with the\r\n             participant's ability to cooperate with the requirements of the study\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Metastatic Non Small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Vibostolimab coformuation","description":"Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years."},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Docetaxel 75 mg^m2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. Docetaxel will serve as part of an experimental treatment in Arm 1, and as an active comparator in Arm 3."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Normal saline IV infusion Q3W up to approximately 2 years"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment","time_frame":"Up to approximately 27 months","description":"PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented"},{"outcome_type":"secondary","measure":"Objective Response (OR) per RECIST 1.1 by BICR Assessment","time_frame":"Up to approximately 27 months","description":"OR is defined as a confirmed complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 77 months","description":"OS is defined as the time from randomization to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 by BICR Assessment","time_frame":"Up to approximately 77 months","description":"For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced an Adverse Event (AE)","time_frame":"Up to approximately 77 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who experience an AE will be reported."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Treatment Due to an AE","time_frame":"Up to approximately 37 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who discontinue study treatment due to an AE will be reported."}]}
{"nct_id":"NCT04853342","start_date":"2021-04-17","phase":"Phase 3","enrollment":318,"brief_title":"To Assess the Efficacy and Safety of Furmonertinib Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy","official_title":"A Phase III, Double-blind, Randomized, Placebo-Controlled Multi-centre, Study to Assess the Efficacy and Safety of Furmonertinib (AST2818) Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-01-31","last_update":"2021-04-21","description":"This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of Furmonertinib (AST2818) versus placebo in patients with stage II-IIIA non-small cell lung cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and L858R) either alone or in combination with other EGFR mutations as confirmed by a central test, who have had complete tumour resection, with or without postoperative adjuvant chemotherapy.","other_id":"ALSC010AST2818","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Male or female, aged at least 18 years.\r\n\r\n          -  Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on\r\n             predominantly non-squamous histology.\r\n\r\n          -  MRI or CT scan of the brain must be done prior to surgery as it is considered standard\r\n             of care.\r\n\r\n          -  Patients must be classified post-operatively as Stage IB, II, or IIIA on the basis of\r\n             pathologic criteria.\r\n\r\n          -  Confirmation by the central laboratory that the tumor harbors one of the 2 common EGFR\r\n             mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either\r\n             alone or in combination with other EGFR mutations including T790M.\r\n\r\n          -  Complete surgical resection of the primary NSCLC is mandatory. All gross disease must\r\n             have been removed at the end of surgery. All surgical margins of resection must be\r\n             negative for the tumor.\r\n\r\n          -  Complete recovery from surgery and standard post-operative therapy (if applicable) at\r\n             the time of randomization.\r\n\r\n          -  World Health Organization Performance Status of 0 to 1.\r\n\r\n          -  Female patients should be using adequate contraceptive measures, should not be\r\n             breastfeeding, and must have a negative pregnancy test prior to the first dose of the\r\n             study drug; or female patients must have evidence of non-child-bearing potential.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Pre-operative or post-operative or planned radiation therapy for the current lung\r\n             cancer\r\n\r\n          -  Pre-operative (neo-adjuvant) platinum-based or other chemotherapy\r\n\r\n          -  Any prior anticancer therapy\r\n\r\n          -  Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time\r\n\r\n          -  Major surgery (including primary tumor surgery, excluding placement of vascular\r\n             access) within 4 weeks of the first dose of study drug\r\n\r\n          -  Patients currently receiving medications or herbal supplements known to be potent\r\n             inducers of cytochrome P450 (CYP) 3A4\r\n\r\n          -  Treatment with an investigational drug within five half-lives of the compound or any\r\n             of its related material.\r\n\r\n          -  Patients who have had only segmentectomies or wedge resections\r\n\r\n          -  History of other malignancies, except: adequately treated non-melanoma skin cancer,\r\n             curatively treated in-situ cancer, or other solid tumors curatively treated with no\r\n             evidence of disease for > 5 years following the end of treatment.\r\n\r\n          -  Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\r\n             starting study treatment with the exception of alopecia and Grade 2, prior\r\n             platinum-therapy related neuropathy.\r\n\r\n          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled\r\n             hypertension and active bleeding diatheses; or active infection including hepatitis B,\r\n             hepatitis C, and human immunodeficiency virus (HIV).\r\n\r\n          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to\r\n             swallow the formulated product, or previous significant bowel resection that would\r\n             preclude adequate absorption of AZD9291.\r\n\r\n          -  Any of the following cardiac criteria:\r\n\r\n          -  Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the\r\n             screening clinic ECG Machine-derived QTc value.\r\n\r\n          -  Any clinically important abnormalities in rhythm, conduction, or morphology of resting\r\n             ECG.\r\n\r\n          -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,\r\n             or unexplained sudden death under 40 years of age in first-degree relatives or any\r\n             concomitant medication known to prolong the QT interval.\r\n\r\n          -  Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required\r\n             steroid treatment, or any evidence of clinically active ILD.\r\n\r\n          -  Inadequate bone marrow reserve or organ function.\r\n      ","sponsor":"Allist Pharmaceuticals, Inc.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Drug: Furmonertinib 80 mg","description":"The initial dose of Furmonertinib 80 mg once daily"},{"intervention_type":"Drug","name":"Drug: Furmonertinib 80 mg placebo","description":"The initial dose of Furmonertinib 80 mg once daily"}],"outcomes":[{"outcome_type":"primary","measure":"DFS","time_frame":"From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence). Estimated median time to event of 60 months for those treatment) [ Time Frame: Up to 5 years]","description":"Disease free survival"},{"outcome_type":"secondary","measure":"Disease free survival (DFS) rate","time_frame":"Time Frame: From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence)Estimated median time to event of 60 months for those treatment[ Time Frame: Up to 5 years]","description":"Disease free survival (DFS) rate at 2, 3 and 5 years"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Time Frame: From date of randomization until date of death due to any cause Estimated median time to event of 60 months for those treatment[ Time Frame: Up to 5 years]","description":"Defined as the time from the date of randomization until date of death due to any cause"},{"outcome_type":"secondary","measure":"Overall Survival rate at 5 years","time_frame":"Time Frame: From date of randomization until date of death due to any cause about 5years[ Time Frame: Up to 5 years]","description":"Defined as the proportion of patients alive at 5 years, estimated from a Kaplan Meier plot of OS at the time of the primary analysis"}]}
{"nct_id":"NCT04730349","start_date":"2021-04-15","phase":"Phase 1/Phase 2","enrollment":228,"brief_title":"A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination With Nivolumab in Children, Adolescents and Young Adults With Recurrent or Treatment-resistant Cancer","official_title":"Phase 1/2 Study of Bempegaldesleukin in Combination With Nivolumab in Children, Adolescents, and Young Adults With Recurrent or Refractory Malignancies (PIVOT IO 020)","primary_completion_date":"2025-10-19","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2025-10-20","last_update":"2021-01-29","description":"The purpose of this study is to first, in Part A, assess the safety, tolerability and drug levels of Bempegaldesleukin (BEMPEG) in combination with nivolumab and then, in Part B, to estimate the preliminary efficacy in children, adolescents and young adults with recurrent or treatment-resistant cancer.","other_id":"CA045-020","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","maximum_age":30,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Age < 18 years for Part A and Part B\r\n\r\n          -  Age up to 30 years for Part B Cohorts B2, B3 and B4\r\n\r\n          -  Must have received standard of care therapy and there must be no potentially curative\r\n             treatment available\r\n\r\n          -  Histologically confirmed with malignant neoplasms that are refractory, relapsed, or\r\n             curative treatments are lacking\r\n\r\n          -  Must have measurable or evaluable disease based on Response Evaluation Criteria in\r\n             Solid Tumors (RECIST) v1.1 for solid tumors, Response Assessment in Neuro-Oncology\r\n             (RANO) or Response Assessment in Pediatric Neuro-Oncology (RAPNO) for central nervous\r\n             system tumors, International Pediatric Non-Hodgkin Lymphoma Response Criteria for\r\n             non-Hodgkin lymphoma (NHL), revised International Neuroblastoma Response Criteria\r\n             (INRC) for neuroblastoma, modified National Comprehensive Cancer Network (NCCN)\r\n             Criteria for acute lymphoblastic leukemia, and modified Cheson et al International\r\n             Working Group criteria for acute myeloid leukemia\r\n\r\n          -  Lansky play score for age  16 years or Karnofsky performance score for age > 16 years\r\n             assessed within 2 weeks of enrollment must be  60\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Osteosarcoma, T-cell/Natural Killer (NK) cell leukemia/lymphoma, and Hodgkin's\r\n             lymphoma\r\n\r\n          -  Need for > 2 antihypertensive medications for management of hypertension (including\r\n             diuretics)\r\n\r\n          -  Known cardiovascular history, including unstable or deteriorating cardiac disease,\r\n             within the previous 12 months prior to screening\r\n\r\n          -  Inadequately treated adrenal insufficiency\r\n\r\n          -  Active, known, or suspected autoimmune disease\r\n\r\n          -  Active infection requiring systemic therapy within 14 days prior to first dose\r\n\r\n          -  Condition requiring systemic treatment with either corticosteroids or other\r\n             immunosuppressive medications within 14 days of start of study treatment\r\n\r\n          -  Prior allogeneic stem cell transplant\r\n\r\n          -  Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either\r\n             suspected or confirmed within 4 weeks prior to screening\r\n\r\n        NOTE: other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Ependymoma|Ewing Sarcoma|High-grade Glioma|Leukemia and Lymphoma|Medulloblastoma|Miscellaneous Brain Tumors|Miscellaneous Solid Tumors|Neuroblastoma|Relapsed, Refractory Malignant Neoplasms|Rhabdomyosarcoma","interventions":[{"intervention_type":"Biological","name":"Biological: Nivolumab","description":"Specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: NKTR-214","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of dose-limiting toxicities","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Incidence of adverse events (AEs)","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Incidence of serious AEs (SAEs)","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Incidence of drug-related AEs","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Incidence of death","time_frame":"Up to 2 years and 100 days","description":"Part A"},{"outcome_type":"primary","measure":"Pharmacokinetic (PK) parameters: Peak concentration","time_frame":"Up to 2 years","description":"Part A"},{"outcome_type":"primary","measure":"Pharmacokinetic (PK) parameters: Trough concentration","time_frame":"Up to 2 years","description":"Part A"},{"outcome_type":"primary","measure":"Pharmacokinetic (PK) parameters: Time-averaged concentration","time_frame":"Up to 2 years","description":"Part A"},{"outcome_type":"primary","measure":"Pharmacokinetic (PK) parameters: Clearance (CL)","time_frame":"Up to 2 years","description":"Part A"},{"outcome_type":"primary","measure":"Pharmacokinetic (PK) parameters: Volume of distribution (Vd)","time_frame":"Up to 2 years","description":"Part A"},{"outcome_type":"primary","measure":"Investigator-assessed objective response rate (ORR)","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of AEs","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of SAEs","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of drug-related AEs","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of death","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of laboratory abnormalities: Hematology tests","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Incidence of laboratory abnormalities: Clinical chemistry tests","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"Up to 5 years","description":"Part B"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 5 years","description":"Part B"}]}
{"nct_id":"NCT04887506","start_date":"2021-04-14","phase":"Phase 3","enrollment":108,"brief_title":"TAVT-45 (Abiraterone Acetate) Granules in Patients With Prostate Cancer","official_title":"Phase 3 Study Investigating the Efficacy and Safety of TAVT-45 (Abiraterone Acetate) Granules for Oral Suspension (Novel Abiraterone Acetate Formulation) Relative to a Reference Abiraterone Acetate Formulation in Patients With mCSPC & mCRPC","primary_completion_date":"2022-04-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-06-30","last_update":"2021-09-01","description":"The purpose of this study is to investigate the safety and efficacy of a new formulation of an existing drug product called TAVT-45 in patients with metastatic prostate cancer.","other_id":"TAVT45C02","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Written informed consent obtained prior to any study-related procedure being performed\r\n\r\n          2. Male patients at least 18 years of age or older at time of consent\r\n\r\n          3. Pathologically confirmed adenocarcinoma of the prostate\r\n\r\n          4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist\r\n             (unless patient has already had a bilateral orchiectomy) AND serum testosterone level\r\n             <50 ng/dL at screening\r\n\r\n          5. Have either metastatic CSPC or metastatic CRPC (per protocol definitions).\r\n\r\n          6. The following prior treatments and/or surgery for prostate cancer are allowed:\r\n\r\n               1. CSPC:\r\n\r\n                    -  Up to 90 days of androgen deprivation therapy (ADT) with\r\n                       gonadotropin-releasing hormone (GnRH) agonists/antagonists or orchiectomy\r\n                       with or without concurrent anti-androgens prior to patients' randomization\r\n                       is permitted\r\n\r\n                    -  Patients may have one course of palliative radiation or surgical therapy to\r\n                       treat symptoms resulting from metastatic disease (e.g., impending cord\r\n                       compression or obstructive symptoms) if administered prior to randomization\r\n\r\n                    -  Radiation or surgical therapy that was not initiated 4 weeks after the start\r\n                       of ADT or orchiectomy\r\n\r\n               2. CRPC:\r\n\r\n                    -  Previous chemotherapy with docetaxel for metastatic disease with treatment\r\n                       completed at least 1 year prior to enrolment\r\n\r\n          7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the\r\n             start of study medication; discontinuation of bicalutamide prior to start of study\r\n             medication\r\n\r\n          8. Discontinuation of strong CYP3A4 inducers at prior to start of study medication\r\n\r\n          9. Discontinuation of radiotherapy prior to start of study medication\r\n\r\n         10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of\r\n             study medication and for the duration of the trial.\r\n\r\n         11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening\r\n\r\n         12. Normal organ function with acceptable initial laboratory values within the screening\r\n             period:\r\n\r\n               -  ANC:  1,500/l\r\n\r\n               -  Albumin:  3.0g/dL\r\n\r\n               -  Hemoglobin:  9g/dL\r\n\r\n               -  Platelet count:  100,000/l\r\n\r\n               -  Serum Creatinine:  3.0 x the institutional upper limit of normal (ULN)\r\n\r\n               -  Potassium:  3.5 mmol/L (within institutional normal range)\r\n\r\n               -  Bilirubin:  1.5 ULN (unless documented Gilbert's disease)\r\n\r\n               -  SGOT (AST):  2.5 x ULN\r\n\r\n               -  SGPT (ALT):  2.5 x ULN\r\n\r\n         13. Life expectancy of at least 6 months at screening\r\n\r\n         14. Patients engaged in sex with women of child-bearing potential agree to use a condom\r\n             plus another effective contraception method. Patients agree to use a condom when\r\n             engaged in any sexual activity, including sex with a pregnant woman. These\r\n             restrictions will apply from the time informed consent is provided until 3 weeks after\r\n             the last dose of study medication is taken.\r\n\r\n         15. Patient is willing and able to comply with all protocol requirements\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. For mCSPC patients: any prior pharmacotherapy, radiation therapy, or surgery for\r\n             metastatic prostate cancer not specified as allowable treatment in Inclusion Criterion\r\n             6. For example, prior therapy with apalutamide or enzalutamide is prohibited as well\r\n             as therapy with an investigational agent as described in Exclusion Criterion 16.\r\n\r\n          2. For mCRPC patients:\r\n\r\n               -  Prior treatment with abiraterone or enzalutamide is prohibited\r\n\r\n               -  Previous chemotherapy is prohibited with exception of docetaxel treatment as\r\n                  specified in the inclusion criteria 6.\r\n\r\n          3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of\r\n             study drug/reference product. Patients who are on a stable dose of these medications\r\n             for at least 4 weeks at the time of starting study drug/reference product will be\r\n             eligible.\r\n\r\n          4. Therapy with estrogen within 4 weeks prior to the start of study drug\r\n\r\n          5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who\r\n             have discontinued or reduced dosing to the equivalent of  10 mg prednisone daily\r\n             within 14 days prior to the start of study drug are eligible\r\n\r\n          6. Known, symptomatic metastases to the brain or central nervous system involvement\r\n             (patients with asymptomatic and neurologically stable disease for the past 4 weeks\r\n             will be permitted)\r\n\r\n          7. History of adrenal gland dysfunction defined as requiring treatment for adrenal\r\n             insufficiency\r\n\r\n          8. History of other malignancy within the previous 2 years (no longer being actively\r\n             treated), with the exceptions of basal cell carcinoma, nonmuscle invasive bladder\r\n             cancer that has been treated and is under surveillance, or other in-situ cancers with\r\n             a low likelihood of recurrence\r\n\r\n          9. Major surgery within 4 weeks prior to the start of study drug\r\n\r\n         10. Known gastrointestinal disease or condition that could impair absorption inclusive of\r\n             gastrocolic fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic\r\n             pancreatitis or pancreatic cancer, cystic fibrosis, lactate deficiency, amyloidosis,\r\n             celiac disease, Crohn's disease, radiation enteritis, intestinal resection, and\r\n             history of bariatric surgery\r\n\r\n         11. Known history of human immunodeficiency virus or seropositive test for hepatitis C\r\n             virus (HCV) or hepatitis B surface antigen (HBsAg) (note: HCV patients with\r\n             undetectable viral load will be eligible)\r\n\r\n         12. Poorly controlled diabetes, defined as HbA1c > 8% within the past 12 months\r\n\r\n         13. Uncontrolled hypertension at screening\r\n\r\n         14. History of New York Heart Association class III or IV heart failure\r\n\r\n         15. Serious concurrent illness, including psychiatric illness, that could interfere with\r\n             study participation\r\n\r\n         16. Receipt of another investigational agent within 4 weeks or 5 x the treatment\r\n             half-life, whichever is longer, of treatment start.\r\n\r\n         17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients\r\n             in the study drugs\r\n\r\n         18. In the opinion of the investigator, participation in the trial would prevent the\r\n             patient from receiving local standard-of-care treatment for metastatic prostate\r\n             cancer, if clinically indicated, after completion of the trial\r\n\r\n         19. Other condition which, in the opinion of the Investigator, would preclude\r\n             participation in this trial.\r\n      ","sponsor":"Tavanta Therapeutics","sponsor_type":"Industry","conditions":"Metastatic Castration-resistant Prostate Cancer|Metastatic Castration-sensitive Prostate Cancer|Metastatic Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TAVT-45","description":"250 mg abiraterone acetate granules for oral suspension in a sachet, administered twice daily."},{"intervention_type":"Drug","name":"Drug: Zytiga","description":"500 mg tablet, administered twice daily."},{"intervention_type":"Drug","name":"Drug: Prednisone","description":"mCSPC patients will receive 5 mg orally once daily. mCRPC patients will receive 5 mg orally twice daily."}],"outcomes":[{"outcome_type":"primary","measure":"Testosterone Levels","time_frame":"Average over Day 9 and Day 10","description":"Blood samples collected to measure serum testosterone in order to demonstrate equivalent pharmacodynamic effect between TAVT-45 and reference abiraterone acetate (R-AA)"},{"outcome_type":"secondary","measure":"Percent of Subjects With PSA-50 Response","time_frame":"Over 84 days","description":"Blood samples collected to measure prostate-specific antigen (PSA). The PSA-50 response is defined as a decrease of ≥ 50% in PSA levels from baseline"},{"outcome_type":"secondary","measure":"Testosterone Levels","time_frame":"Days 28, 56 and 84","description":"Blood samples collected to measure serum testosterone levels"},{"outcome_type":"secondary","measure":"Percent of Subjects With PSA-50 Response","time_frame":"Days 28, 56, and 84","description":"Blood samples collected to measure PSA in order to determine PSA-50"},{"outcome_type":"secondary","measure":"PSA Levels","time_frame":"Days 28, 56, and 84","description":"Blood samples collected to measure PSA"},{"outcome_type":"secondary","measure":"Trough concentrations of abiraterone","time_frame":"Days 9, 28, 56, and 84","description":"Blood samples collected to measure plasma concentrations of abiraterone (trough sample to be collected before next dose)"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of AUC","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of Cmax","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of Cmin","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of Tmax","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of Rac","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"},{"outcome_type":"secondary","measure":"Pharmacokinetic analysis of t1/2","time_frame":"Days 1 and 9","description":"Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling"}]}
{"nct_id":"NCT04736706","start_date":"2021-04-14","phase":"Phase 3","enrollment":1431,"brief_title":"A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)","official_title":"An Open-label, Randomized Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or MK-1308A in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, as First-Line Treatment in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)","primary_completion_date":"2026-10-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-10-29","last_update":"2021-09-17","description":"The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.","other_id":"6482-012","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has histologically confirmed diagnosis of RCC with clear cell component\r\n\r\n          -  Has received no prior systemic therapy for advanced ccRCC\r\n\r\n          -  Male participants are abstinent from heterosexual intercourse or agree to use\r\n             contraception during and for at least 7 days after last dose of study intervention\r\n             with belzutifan and lenvatinib\r\n\r\n          -  Female participants are not pregnant or breastfeeding and are either not a woman of\r\n             child-bearing potential (WOCBP) or use a contraceptive method that is highly effective\r\n             or are abstinent from heterosexual intercourse during the intervention period and for\r\n             at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30\r\n             days after last dose of lenvatinib or belzutifan, whichever occurs last\r\n\r\n          -  Has adequately controlled blood pressure with or without antihypertensive medications\r\n\r\n          -  Has adequate organ function\r\n\r\n          -  Participants receiving bone resorptive therapy must have therapy initiated at least 2\r\n             weeks prior to randomization/allocation\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years\r\n\r\n          -  Has had major surgery, other than nephrectomy within 4 weeks prior to randomization\r\n\r\n          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis\r\n\r\n          -  Has received prior radiotherapy within 2 weeks prior to first dose of study\r\n             intervention\r\n\r\n          -  Has hypoxia or requires intermittent supplemental oxygen or requires chronic\r\n             supplemental oxygen\r\n\r\n          -  Has clinically significant cardiac disease within 12 months from first dose of study\r\n             intervention\r\n\r\n          -  Has a history of interstitial lung disease\r\n\r\n          -  Has symptomatic pleural effusion; a participant who is clinically stable following\r\n             treatment of this condition is eligible\r\n\r\n          -  Has preexisting gastrointestinal or non-gastrointestinal fistula\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             or any other form of immunosuppressive therapy within 7 days prior to the first dose\r\n             of study treatment\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with\r\n             requirements of the study\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study drug; killed vaccines are allowed\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in the past 2\r\n             years\r\n\r\n          -  Has a history of noninfectious pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known history of human immunodeficiency virus (HIV) infection\r\n\r\n          -  Has a known history of Hepatitis B\r\n\r\n          -  Has radiographic evidence of intratumoral cavitation, encasement or invasion of a\r\n             major blood vessel\r\n\r\n          -  Has clinically significant history of bleeding within 3 months prior to randomization\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Carcinoma, Renal Cell","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Pembrolizumab 400 mg administered Q6W via IV infusion"},{"intervention_type":"Drug","name":"Drug: Belzutifan","description":"Belzutifan 120 mg administered QD via oral tablet"},{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Quavonlimab","description":"Pembrolizumab/quavonlimab is a co-formulated product composed of pembrolizumab 400 mg in combination with quavonlimab 25 mg, administered Q6W via IV infusion"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib 20 mg administered QD via oral capsule"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 46 months","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR based on RECIST 1.1 will be presented."},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 66 months","description":"OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 46 months","description":"ORR is defined as the percentage of participants who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR","time_frame":"Up to approximately 66 months","description":"For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced At least One Adverse Event (AE)","time_frame":"Up to approximately 66 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinue Study Treatment Due to an AE","time_frame":"Up to approximately 66 months","description":"An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented."}]}
{"nct_id":"NCT04738487","start_date":"2021-04-07","phase":"Phase 3","enrollment":598,"brief_title":"Coformulation of Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab (MK-3475) Monotherapy for Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Metastatic Non-Small Cell Lung Cancer (MK-7684A-003)","official_title":"A Phase 3, Multicenter, Randomized, Double-Blind Study of MK-7684 With Pembrolizumab as a Coformulation (MK-7684A) Versus Pembrolizumab Monotherapy as First Line Treatment for Participants With PD-L1 Positive Metastatic Non-Small Cell Lung Cancer","primary_completion_date":"2025-04-04","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-04-29","last_update":"2021-09-20","description":"The primary hypotheses are that coformulated pembrolizumab/vibostolimab is superior to pembrolizumab alone with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by blinded independent central review (BICR), and with respect to overall survival (OS), in participants with non-small cell lung cancer.","other_id":"7684A-003","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has a histologically or cytologically confirmed diagnosis of Stage IV: M1a, M1b, or\r\n             M1c non-small cell lung cancer (NSCLC) per the American Joint Committee on Cancer\r\n             (AJCC) Staging Manual, version 8\r\n\r\n          -  Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\r\n             1.1, as determined by the local site assessment\r\n\r\n          -  Has confirmation that epidermal growth factor receptor (EGFR)-, anaplastic lymphoma\r\n             kinase (ALK)-, or reactive oxygen species proto-oncogene 1 (ROS1)-directed therapy is\r\n             not indicated as primary therapy and absence of ALK and ROS1 gene rearrangements\r\n\r\n          -  Has provided tumor tissue that demonstrates Programmed Cell Death 1 Ligand 1 (PD-L1)\r\n             expression in 1% of tumor cells as assessed by immunohistochemistry (IHC) at a\r\n             central laboratory\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 assessed\r\n             within 7 days prior to randomization\r\n\r\n          -  Has a life expectancy of at least 3 months\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant or\r\n             breastfeeding, and at least one of the following conditions applies:\r\n\r\n               -  Is not a woman of childbearing potential (WOCBP)\r\n\r\n               -  Is a WOCBP and using a contraceptive method that is highly effective (with a\r\n                  failure rate of <1% per year), with low user dependency or be abstinent from\r\n                  heterosexual intercourse as their preferred and usual lifestyle (abstinent on a\r\n                  long term and persistent basis), during the intervention period and for at least\r\n                  120 days after the last dose of study intervention\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a known history of an additional malignancy, except if the participant has\r\n             undergone potentially curative therapy with no evidence of that disease recurrence for\r\n             at least 3 years since initiation of that therapy\r\n\r\n          -  Has received prior systemic chemotherapy or other targeted or biological\r\n             antineoplastic therapy for their metastatic NSCLC.\r\n\r\n               -  Prior treatment with chemotherapy and/or radiation as part of\r\n                  neoadjuvant/adjuvant or chemoradiation therapy for nonmetastatic NSCLC is allowed\r\n                  as long as therapy was completed at least 6 months before the diagnosis of\r\n                  metastatic NSCLC.\r\n\r\n               -  Participants must have recovered from all AEs due to previous therapies to Grade\r\n                  1 or baseline. Participants with Grade 2 neuropathy may be eligible.\r\n                  Participants with endocrine-related AEs Grade 2 requiring treatment or hormone\r\n                  replacement may be eligible.\r\n\r\n          -  Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1),\r\n             anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death\r\n             receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or\r\n             co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4\r\n             (CTLA-4), OX-40, CD137)\r\n\r\n          -  Has received previous treatment with another agent targeting the T cell immunoreceptor\r\n             with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM)\r\n             domains (TIGIT) receptor pathway\r\n\r\n          -  Has received radiotherapy within 2 weeks of start of study intervention. Participants\r\n             must have recovered from all radiation-related toxicities, not require\r\n             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted\r\n             for palliative radiation (2 weeks of radiotherapy) to non-central nervous system\r\n             (CNS) disease\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days prior to the first dose\r\n             of study intervention. Administration of killed vaccines is allowed\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks prior to the first dose of\r\n             study intervention\r\n\r\n          -  Has known active or untreated CNS metastases and/or carcinomatous meningitis.\r\n             Participants with previously treated brain metastases may participate provided they\r\n             are radiologically stable for at least 4 weeks by repeat imaging, clinically stable,\r\n             and without requirement of steroid treatment for at least 14 days prior to first dose\r\n             of study intervention\r\n\r\n          -  Has severe hypersensitivity (Grade 3) to pembrolizumab/vibostolimab or pembrolizumab\r\n             and/or any of its excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n             (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive\r\n             drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid\r\n             replacement therapy for adrenal or pituitary insufficiency) is not considered a form\r\n             of systemic treatment and is allowed.\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior to the first dose of study intervention\r\n\r\n          -  Has a history of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is\r\n             not exclusionary.\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is\r\n             required unless mandated by local health authority\r\n\r\n          -  Has a known history of Hepatitis B or known active Hepatitis C virus infection\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with the\r\n             participant's ability to cooperate with the requirements of the study\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Lung Neoplasms|Non-Small-Cell Lung Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Vibostolimab","description":"Coformulation of pembrolizumab (MK-3475) 200mg and vibostolimab (MK-7684) 200mg. Participants receive the coformulation by intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 administrations."},{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Participants receive 200 mg of pembrolizumab by intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 administrations."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-Free Survival (PFS)","time_frame":"Up to approximately 38 months","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented."},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 46 months","description":"OS is defined as the time from randomization to death due to any cause"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to approximately 2 years","description":"ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to approximately 46 months","description":"For participants who demonstrate a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by blinded independent central review will be presented."},{"outcome_type":"secondary","measure":"Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 (\"How would you rate your overall health during the past week?\" and \"How would you rate your overall quality of life during the past week?\") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome."},{"outcome_type":"secondary","measure":"Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"Change from baseline in the score of EORTC QLQ-C30 Items 1-5 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function."},{"outcome_type":"secondary","measure":"Change from Baseline in Dyspnea Score (Item 8) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"Change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Were you short of breath?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea."},{"outcome_type":"secondary","measure":"Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)","time_frame":"Baseline and up to approximately 107 weeks","description":"Change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Have you coughed?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing."},{"outcome_type":"secondary","measure":"Change from Baseline in Chest Pain Score (Item 40) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)","time_frame":"Baseline and up to approximately 107 weeks","description":"Change from baseline in the score of EORTC QLQ-C13 Item 40 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Have you had pain in your chest?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"TTD in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 (\"How would you rate your overall health during the past week?\" and \"How would you rate your overall quality of life during the past week?\") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline."},{"outcome_type":"secondary","measure":"TTD in Physical Functioning (Items 1-5) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"TTD in the score of EORTC QLQ-C30 Items 1-5 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline."},{"outcome_type":"secondary","measure":"TTD in Dyspnea Score (Item 8) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)","time_frame":"Baseline and up to approximately 107 weeks","description":"TTD in the score of EORTC QLQ-C30 Item 8 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Were you short of breath?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline."},{"outcome_type":"secondary","measure":"TTD in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)","time_frame":"Baseline and up to approximately 107 weeks","description":"TTD in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Have you coughed?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline."},{"outcome_type":"secondary","measure":"TTD in Chest Pain Score (Item 40) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)","time_frame":"Baseline and up to approximately 107 weeks","description":"TTD in the score of EORTC QLQ-C13 Item 40 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question \"Have you had pain in your chest?\" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced One or More Adverse Events (AEs)","time_frame":"Up to approximately 115 weeks","description":"The number of participants who experienced an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)","time_frame":"Up to approximately 103 weeks","description":"The number of participants who discontinue study intervention due to an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment."}]}
{"nct_id":"NCT04829604","start_date":"2021-04-05","phase":"Phase 2","enrollment":200,"brief_title":"ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)","official_title":"A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients Whose Disease is Resistant or Refractory to T-DM-1 or T-DXd, and/or Tucatinib-containing Regimens","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-02-28","last_update":"2021-09-09","description":"A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose Disease is Resistant or Refractory to T-DM1, and/or T-DXd, and/or Tucatinib-containing Regimens","other_id":"ACE-Breast-03","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"One single arm, open label with intravenous infusion of ARX788","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Age  18 years and older\r\n\r\n          -  Life expectancy > 3 months\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status  1\r\n\r\n          -  Metastatic breast cancer subjects previously treated with T DM1, and/or T-DXd, and/or\r\n             tucatinib-containing regimens.\r\n\r\n          -  Presence of at least one measurable lesion per RECIST v 1.1\r\n\r\n          -  Subjects must have an adequate tumor sample available for confirmation of HER2 status\r\n\r\n          -  Subjects with stable brain metastases\r\n\r\n          -  Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved\r\n             to Grade 1 as per the NCI-CTCAE v 5.0, except alopecia.\r\n\r\n          -  Adequate organ functions\r\n\r\n          -  Willing and able to understand and sign an informed consent inform and to comply with\r\n             all aspects of the protocol.\r\n\r\n          -  Female subjects must be surgically sterile, or have a monogamous partner who is\r\n             surgically sterile, or at postmenopausal, or who commits to use an acceptable form of\r\n             birth control; male subjects must be sterile (biologically or surgically) or commit to\r\n             the use of a reliable method of birth control\r\n\r\n        Exclusion Criteria:\r\n\r\n        Any subject who meets any of the following criteria is excluded from the study:\r\n\r\n          -  History of allergic reactions to any component of ARX788.\r\n\r\n          -  Prior history of interstitial lung disease, pneumonitis, or other clinically\r\n             significant lung disease within 12 months\r\n\r\n          -  History of ocular events, or any current ongoing active ocular infections.\r\n\r\n          -  History of congestive heart failure, unstable angina pectoris, unstable atrial\r\n             fibrillation, or cardiac arrhythmia within 12 months prior to enrollment\r\n\r\n          -  Grade 2 to 4 peripheral neuropathy (NCI CTCAE v 5.0)\r\n\r\n          -  History of unstable central nervous system (CNS) metastases\r\n\r\n          -  Current severe, uncontrolled systemic disease (eg, clinically significant\r\n             cardiovascular, pulmonary, or metabolic diseases)\r\n\r\n          -  Any uncontrollable intercurrent illness, infection (including subjects with active,\r\n             symptomatic Covid-19 infections), or other conditions that could limit study\r\n             compliance or interfere with assessments.\r\n\r\n          -  Exposure to any other investigational or commercial anticancer agents or therapies\r\n             administered with the intention to treat malignancy within 14 days before the first\r\n             dose of ARX788.\r\n\r\n          -  Clinically significant surgical intervention (excluding diagnostic biopsy) within 21\r\n             days of the first dose of ARX788\r\n\r\n          -  Radiotherapy administered less than 21 days prior to the first dose of ARX788, or\r\n             localized palliative radiotherapy administered less than 7 days prior to the first\r\n             dose of ARX788, or radiotherapy-induced toxicity of Grade 2 or greater based on\r\n             NCI-CTCAE v 5.0.\r\n\r\n          -  Pregnancy or breast feeding.\r\n\r\n          -  Known active HCV, HBV, and/or HIV infection.\r\n      ","sponsor":"Ambrx, Inc.","sponsor_type":"Industry","conditions":"HER2 Positive Metastatic Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: ARX788","description":"The active pharmaceutical ingredient in ARX788 is an antibody drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody (mAb) (IgG1) covalently conjugated to two microtubule-disrupting payloads AS269"}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate (ORR)","time_frame":"2 Years","description":"The confirmed objective response rate (ORR) of ARX788 based on RECIST 1.1 in HER2-positive breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens.\r\nThe ORR is defined as the number of subjects with a BOR of CR or PR divided by the number of response evaluable subjects."},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"2 years","description":"DOR is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first, will be computed for subjects with a BOR of CR or PR."},{"outcome_type":"secondary","measure":"Best percent change in the sum of the longest diameters of measurable tumors","time_frame":"2 years","description":"The percent change at the best response data point compared to baseline."},{"outcome_type":"secondary","measure":"Best overall response (BOR)","time_frame":"2 year","description":"BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started)"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"2 years","description":"DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"2 years","description":"PFS is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first, will be computed for response evaluable subjects. Subjects will be censored at time of subsequent therapy"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"2 year","description":"Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). Subjects who are alive will be censored at the last known time that the subject was alive."},{"outcome_type":"secondary","measure":"The number of subjects experiencing adverse event TEAEs","time_frame":"2 years","description":"Patient safety and adverse events (AEs) will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. All AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the treatment."},{"outcome_type":"secondary","measure":"Maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269","time_frame":"Cycle 1 and cycle 3","description":"Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269"},{"outcome_type":"secondary","measure":"Trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269","time_frame":"Cycle 1 and cycle 3","description":"Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269"},{"outcome_type":"secondary","measure":"Area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269","time_frame":"Cycle 1 and cycle 3","description":"Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269"},{"outcome_type":"secondary","measure":"Incidence of anti-drug antibodies (ADAs)","time_frame":"2 years","description":"Incidence of anti-drug antibodies (ADAs) following intravenous administration of ARX788 in participants with HER2-positive metastatic breast cancer"}]}
{"nct_id":"NCT04680988","start_date":"2021-04-04","phase":"Phase 2","enrollment":250,"brief_title":"A Study of SHR-1210 SHR-1020 Versus Chemotherapy in Patients With Recurrent or Metastatic Cervical Cancer","official_title":"A Randomized,Open-label, Multi-Center, Phase II Clinical Trial to Assess the Efficacy and Safety of SHR-1210 SHR-1020 Versus Physician's Choice Chemotherapy in the Treatment of Recurrent or Metastatic Cervical Cancer Patients","primary_completion_date":"2022-04-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-02-01","last_update":"2021-04-23","description":"This is a randomized, open-label, 3-arm Phase 2 study to evaluate the efficacy and safety of SHR-1210 alone or with SHR-1020 versus physician's choice chemotherapy in recurrent or metastatic cervical cancer patients. All enrolled patients will be randomly divided into 3 groups and receive treatment until disease progression, intolerable toxicityany criterion for stopping the study drug or SHR-1210 treatment for up to 2 years.","other_id":"SHR-1210-II-217","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Voluntarily agree to participate by giving written informed consent.\r\n\r\n          2. Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma,\r\n             adenosquamous carcinoma, or adenocarcinoma of the cervix.\r\n\r\n          3. The patients relapsed after a platinum-based treatment regimen for recurrent or\r\n             metastatic disease.\r\n\r\n          4. Patients must provide a fresh biopsy. If not, sufficient and adequate tumor tissue\r\n             sample from the most recent biopsy of a tumor lesion will be required for PD-L1\r\n             expression.\r\n\r\n          5. Has measurable lesion on imaging based on RECIST version 1.1.\r\n\r\n          6. Have a life expectancy of at least 3 months.\r\n\r\n          7. ECOG performance status 0-1.\r\n\r\n          8. If childbearing potential, female patients must be willing to use at least 1 adequate\r\n             barrier methods throughout the study, starting with the screening visit through 6\r\n             months after the last dose of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has any malignancy <5 years prior to study entry. Except for curative skin basal cell\r\n             carcinoma, carcinoma in situ or breast cancer >3 years.\r\n\r\n          2. Has received prior therapy with: anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte\r\n             antigen 4 (CTLA-4) antibodies; Famitinib; patient is allergic to monoclonal antibody.\r\n\r\n          3. Known to have autoimmune disease.\r\n\r\n          4. Recived other anticancerthera 4 weeks before randomization.\r\n\r\n          5. Known to be human immunodeficiency virus positive, active hepatitis B virus, or active\r\n             hepatitis C virus.\r\n\r\n          6. Untreated and/or uncontrolled brain metastases.\r\n\r\n          7. With high risk of vaginal bleeding or gastrointestinal perforation.\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Recurrent or Metastatic Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: SHR-1210","description":"SHR-1210 intravenously every 3 weeks"},{"intervention_type":"Drug","name":"Drug: SHR-1020","description":"SHR-1020 Orally once daily"},{"intervention_type":"Drug","name":"Drug: Physician's choice chemotherapy","description":"Investigators will declare one of the following regimens:Albumin-bound paclitaxel injection, Pemetrexed disodium for injection, Gemcitabine for injection"}],"outcomes":[{"outcome_type":"primary","measure":"Progression free survival(PFS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus SHR-1210)","time_frame":"Up to 2 years","description":"The time from randomization to disease progression or death. Defined as progression free survival per RECIST 1.1 criteria"},{"outcome_type":"primary","measure":"Overall survival(OS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus Physician's choice chemotherapy)","time_frame":"Up to 2 years","description":"The time interval from the start of treatment to death due to any reason"},{"outcome_type":"secondary","measure":"Progression free survival(PFS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus Physician's choice chemotherapy)","time_frame":"Up to 2 years","description":"The time from randomization to disease progression or death. Defined as progression free survival per RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to 2 years","description":"The best overall response (BOR) of complete response (CR) or partial response (PR). BOR is according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Up to 2 years","description":"The best overall response (BOR) of complete response (CR), partial response (PR) or Stable disease (SD). clinical efficacy evaluation is according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Up to 2 years","description":"The period of time from the date of first documented tumor response (evaluated according to the RECIST v1.1 criteria) to the date of first documented disease progression (evaluated according to RECIST v1.1 criteria) or death of any cause"},{"outcome_type":"secondary","measure":"Time to response (TTR)","time_frame":"Up to 2 years","description":"The time from randomization to the date of first documented response of either CR or PR, according to RECIST 1.1 criteria"},{"outcome_type":"secondary","measure":"Time to treatment failure (TTF)","time_frame":"Up to 2 years","description":"The time from randomization to the end of treatment or death due to any cause"},{"outcome_type":"secondary","measure":"Overall survival(OS) in recurrent or metastatic cervical cancer patients(SHR-1210+SHR-1020 versus SHR-1210)","time_frame":"Up to 2 years","description":"The time interval from the start of treatment to death due to any reason"},{"outcome_type":"secondary","measure":"Adverse Events (AEs)","time_frame":"From the first drug administration to within 90 days for the last treatment dose","description":"Adverse Events per CTCAE v5.0 criteria"},{"outcome_type":"secondary","measure":"Tolerance","time_frame":"From the first drug administration to the last treatment dose","description":"To calculate the proportion of dose interruption, dose reduction or dose termination because of drug-related toxicity"}]}
{"nct_id":"NCT04675294","start_date":"2021-04-02","phase":"Phase 2","enrollment":111,"brief_title":"Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03).","official_title":"A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03).","primary_completion_date":"2023-10-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-10-31","last_update":"2021-08-20","description":"A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma.","other_id":"AT148003","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC)\r\n             that is PD-L1 positive (CPS > 1) and who have not received prior systemic therapy for\r\n             their advanced disease. .\r\n\r\n          -  Adequate Bone Marrow Function.\r\n\r\n          -  Adequate Renal & Liver Function.\r\n\r\n          -  Adequate Performance Status\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Patients with known symptomatic CNS metastases or leptomeningeal disease requiring\r\n             steroids.\r\n\r\n          -  History of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis.\r\n\r\n          -  Prior treatment with any anti-CD47 or anti-SIRP agent.\r\n\r\n          -  Prior treatment with anti-PD-1 or PD-L1.\r\n      ","sponsor":"ALX Oncology Inc.","sponsor_type":"Industry","conditions":"Head and Neck Cancer|Head and Neck Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Evorpacept","description":"IV Q3W"},{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"IV Q3W"}],"outcomes":[{"outcome_type":"primary","measure":"Objective response rate per RECIST 1.1","time_frame":"Last randomized patient reaching at least 24 weeks of follow-up."}]}
{"nct_id":"NCT04639180","start_date":"2021-04-01","phase":"Phase 3","enrollment":674,"brief_title":"A Study to Evaluate Camrelizumab Plus Rivoceranib (Apatinib) as Adjuvant Therapy in Patients With Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation","official_title":"A Randomized, Open-Label, Multi-Center, Phase  Clinical Study of Camrelizumab Plus Rivoceranib (Apatinib) as Adjuvant Therapy in Patients With Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation","primary_completion_date":"2024-07-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-07-31","last_update":"2021-08-19","description":"A Trial to Evaluate the Efficacy and Safety of Camrelizumab Plus Rivoceranib (Apatinib) Versus Active Surveillance as Adjuvant Therapy in Patients with Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation.","other_id":"SHR-1210-III-325","allocation":"Randomized","intervention_model":"Crossover Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"Camrelizumab Combined with Rivoceranib (Apatinib) Versus Active Surveillance","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Subjects with a histopathological diagnosis of HCC\r\n\r\n          -  Subjects who have undergone a curative resection or ablation (radiofrequency ablation\r\n             [RFA] or microwave ablation [MVA] only)\r\n\r\n          -  No previous systematic treatment and locoregional therapy for HCC prior to\r\n             randomization\r\n\r\n          -  Absence of major macrovascular invasion\r\n\r\n          -  No extrahepatic spread\r\n\r\n          -  Full recovery from Curative resection or ablation within 4 weeks prior to\r\n             randomization\r\n\r\n          -  High risk for HCC recurrence after resection or ablation\r\n\r\n          -  For patients who received post-operative transarterial chemoembolization: full\r\n             recovery from the procedure within 4 weeks prior to randomization\r\n\r\n          -  Child-Pugh Class: Grade A\r\n\r\n          -  ECOG-PS score: 0 or 1\r\n\r\n          -  Subjects with HCV- RNA (+) must receive antiviral therapy\r\n\r\n          -  Adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and\r\n             fibrolamellar HCC; other active malignant tumor except HCC within 5 years or\r\n             simultaneously\r\n\r\n          -  Evidence of residual lesion, recurrence, and metastasis at randomization;\r\n\r\n          -  Moderate-to-severe ascites with clinical symptoms\r\n\r\n          -  History of hepatic encephalopathy\r\n\r\n          -  History of gastrointestinal hemorrhage within 6 months prior to the start of study\r\n             treatment or clear tendency of gastrointestinal haemorrhage\r\n\r\n          -  Active or history of autoimmune disease\r\n\r\n          -  Interstitial lung disease that is symptomatic or may interfere with the detection and\r\n             management of suspected drug-related pulmonary toxicity\r\n\r\n          -  Cardiac clinical symptom or cardiovascular disease that is not well controlled\r\n\r\n          -  Severe infection within 4 weeks prior to the start of study treatment\r\n\r\n          -  HIV infection\r\n\r\n          -  Known history of serious allergy to any monoclonal antibody or targeted\r\n             anti-angiogenic drug\r\n\r\n          -  Subjects with inadequately controlled hypertension or history of hypertensive crisis\r\n             or hypertensive encephalopathy\r\n\r\n          -  Thrombosis or thromboembolic event within 6 months prior to the start of study\r\n             treatment\r\n\r\n          -  Known genetic or acquired hemorrhage or thrombotic tendency\r\n\r\n          -  Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6\r\n             months prior to the start of study treatment\r\n\r\n          -  Serious non-healing or dehiscing wound\r\n\r\n          -  Major Curative procedure within four weeks\r\n\r\n          -  Factors to affect oral administration\r\n\r\n          -  Previous or current presence of metastasis to central nervous system\r\n      ","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","sponsor_type":"Industry","conditions":"Hepatocellular Carcinoma (HCC)","interventions":[{"intervention_type":"Drug","name":"Drug: Camrelizumab","description":"Subjects receive Camrelizumab intravenously, Dosage form: lyophilized powder"},{"intervention_type":"Drug","name":"Drug: Rivoceranib (Apatinib)","description":"Subjects receive Rivoceranib (Apatinib) orally, Dosage form: tablet"}],"outcomes":[{"outcome_type":"primary","measure":"Recurrence-Free Survival (RFS), as Determined by the blinded independent review committee (BIRC)","time_frame":"Randomization up to approximately 43 months","description":"RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by BIRC, or death from any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"RFS Rate at 24 and 36 Months, as Assessed by the Investigator","time_frame":"Randomization up to 24 months and up to 36 months"},{"outcome_type":"secondary","measure":"Time to Recurrence (TTR) as determined by the investigator and by BIRC","time_frame":"Randomization up to approximately 43 months","description":"TTR defined as the time from randomization to first documented occurrence of local, regional, or metastatic HCC"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Randomization up to approximately 43 months","description":"OS is defined as the time from randomization to death from any cause"},{"outcome_type":"secondary","measure":"The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0","time_frame":"Baseline up to approximately 43 months"}]}
{"nct_id":"NCT04759664","start_date":"2021-03-31","phase":"Phase 2","enrollment":117,"brief_title":"LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC","official_title":"A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Topically Administered LUT014 in Metastatic Colorectal Cancer Patients With EGFR Inhibitor Induced Acneiform Lesions","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2023-03-31","last_update":"2021-02-18","description":"The study evaluates the efficacy and safety of two strengths of LUT014 Gel topically applied once a day for 4 weeks, compared to placebo, in metastatic colorectal cancer (mCRC) patients who developed Grade 2 EGFRI induced acneiform lesions","other_id":"L-02-01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Diagnosed with mCRC;\r\n\r\n          2. Currently being treated with an FDA approved monoclonal antibody EGFRI for the\r\n             treatment of mCRC, including but not limited to Erbitux (cetuximab) Injection and\r\n             Vectibix (panitumumab) Injection, as directed by the approved labeling;\r\n\r\n          3. Grade 2 acneiform lesions at the Screening and Baseline;\r\n\r\n          4. A score of no more than 40 for the skin-specific questions (first 13 questions) of the\r\n             FACT-EGFRI-18 HRQoL questionnaire at the Screening and Baseline;\r\n\r\n          5. Age 18 years at the time of signing the informed consent form (ICF);\r\n\r\n          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;\r\n\r\n          7. Expected life expectancy greater than 3 months;\r\n\r\n          8. Subject can understand and sign the ICF, can communicate with the Investigator, can\r\n             understand and comply with the requirements of the protocol, and can apply the study\r\n             drug by himself/herself or has a care giver that can apply the drug;\r\n\r\n          9. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at\r\n             Screening and a negative urine pregnancy test at Baseline (Day 0);\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Active infection;\r\n\r\n          2. Significant skin disease other than EGFRI induced acneiform lesions;\r\n\r\n          3. Has a beard that would interfere with administration of study drug and assessment of\r\n             study endpoints (scoring of lesions);\r\n\r\n          4. Any cancer other than mCRC within 3 years of Screening, except for carcinoma in situ\r\n             of the cervix;\r\n\r\n          5. Any condition which, in the opinion of the Investigator, places the subject at\r\n             unacceptable risk if he/she were to participate in the study;\r\n\r\n          6. Clinically relevant serious co-morbid medical conditions including, but not limited\r\n             to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension,\r\n             uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary\r\n             disease, active central nervous system (CNS) disease uncontrolled by standard of care,\r\n             known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B\r\n             or C, cirrhosis, or psychiatric illness/social situations that would limit compliance\r\n             with study requirements;\r\n\r\n          7. Pregnant or lactating;\r\n\r\n          8. Treatment with an EGFRI other than the FDA approved monoclonal antibody EGFRI for the\r\n             treatment of mCRC within 30 days or 5 half-lives of the drug prior to Screening,\r\n             whichever is longer;\r\n\r\n          9. Treatment with a serine/threonine-protein kinase B-Raf (B-Raf) inhibitor, including\r\n             but not limited to Zelboraf (vemurafenib), Tafinlar (dabrafenib), Braftovi\r\n             (encorafenib), and Nexavar (sorafenib), within 30 days or 5 half-lives of the drug\r\n             prior to Screening, whichever is longer. Patients whose mCRC is being treated with a\r\n             monoclonal antibody EGFRI in combination with a B-Raf inhibitor, such as Erbitux\r\n             (cetuximab) Injection in combination with Braftovi (encorafenib) Capsules, will not\r\n             be eligible to participate in this trial;\r\n\r\n         10. Treatment with a systemic corticosteroid or treatment with a topical corticosteroid to\r\n             the face, neck, or upper portion of the anterior or posterior chest within 14 days\r\n             prior to Baseline (Day 0). Patients receiving systemic corticosteroids for 24 hours or\r\n             less only at the time of chemotherapy infusions (for the prevention or treatment of\r\n             chemotherapy-induced nausea and vomiting) will be allowed to enroll into this study;\r\n\r\n         11. Treatment with a topical antibiotic to the face, neck, or upper portion of the\r\n             anterior or posterior chest within 7 days prior to Baseline (Day 0);\r\n\r\n         12. Initiation of treatment with systemic antibiotic(s) < 28 days prior to Baseline (Day\r\n             0) or any change in dose or frequency of systemic antibiotic(s) within 28 days prior\r\n             to Baseline. Patients that undergo a washout from systemic antibiotic(s) will be\r\n             allowed to participate in this trial as long as no systemic antibiotics are taken\r\n             within 7 days prior to Baseline and they meet all other eligibility criteria;\r\n\r\n         13. Treatment with any other topical medication applied to the face, neck, or upper\r\n             portion of the anterior or posterior chest within 7 days prior to Baseline (Day 0).\r\n\r\n         14. Treatment with another investigational drug within 30 days or 5 half-lives of drug\r\n             prior to Screening, whichever is longer;\r\n\r\n         15. Known hypersensitivity to the inactive ingredients of the study drug (active or\r\n             placebo).\r\n      ","sponsor":"Lutris Pharma Ltd.","sponsor_type":"Industry","conditions":"EGFRI Induced Acneiform Lesions","interventions":[{"intervention_type":"Drug","name":"Drug: LUT014 Gel (Dose 1)","description":"Topical gel"},{"intervention_type":"Drug","name":"Drug: LUT014 Gel (Dose 2)","description":"Topical gel"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"LUT014 matching placebo topical gel"}],"outcomes":[{"outcome_type":"primary","measure":"The proportion of subjects in each treatment group who reached treatment success","time_frame":"Four weeks (28 days)","description":"Treatment success will be defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to Day 28, based on CTCAE V5.0 skin and subcutaneous tissue disorders grading scale OR an improvement (increase) of at least 5 points in the total score for the skin-specific (first 13 questions) of the FACT-EGFRI-18 HRQoL questionnaire, from baseline to Day 28, with the exception of subjects who:\r\ntheir dose of EGFRI was decreased, delayed, or stopped during the RDPBC treatment period\r\ninitiated treatment with topical or systemic antibiotic(s) for the treatment of their acneiform lesions during the RDPBC treatment period\r\nexperience an increase in the dose or frequency of the systemic antibiotic(s) relative to Baseline during the RDPBC treatment period\r\nare discontinued from study drug (active or placebo) during the RDBPC treatment period due to worsening of their acneiform lesions"},{"outcome_type":"secondary","measure":"Change in the severity of acneiform lesions based on CTCAE grading scale from baseline to Days 7, 14, 21, 28, and 55. For subjects enrolled in the OLE, the change from pre-dose Day 28 to Days 35, 42, 49, 56, and 84 will also be evaluated;","time_frame":"8-16 weeks (56-84 days)"},{"outcome_type":"secondary","measure":"Change in the FACT-EGFRI-18 questionnaire total score for the skin-specific questions from baseline to Days 7, 14, 21, 28, and 55. For subjects enrolled in the OLE, the change from pre-dose Day 28 to Days 35, 42, 49, 56, and 84 will also be evaluated;","time_frame":"8 -16 weeks (56-84 days)"},{"outcome_type":"secondary","measure":"Relative change in the FACT-EGFRI-18 HRQoL questionnaire","time_frame":"8 weeks (56 days)","description":"Relative change in the FACT-EGFRI-18 score for the skin-specific questions from D0 to D7,14,21,28, 55 compared to the maximal possible improvement in the score from D0; and the relative change from D28 to D35,42,49,56,84 compared to the maximal possible improvement in the score from D28 for OLE subjects."},{"outcome_type":"secondary","measure":"Proportion of subjects whose dose of EGFRI was decreased, delayed, or stopped during the RDPBC and the OLE treatment period","time_frame":"4 weeks (28 days)"},{"outcome_type":"secondary","measure":"Number of AEs and the number and percentage of subjects with AEs","time_frame":"8 weeks (6 days)"}]}
{"nct_id":"NCT04732494","start_date":"2021-03-31","phase":"Phase 2","enrollment":280,"brief_title":"AdvanTIG-203: Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) in Participants With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma","official_title":"A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Compare the Efficacy of Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Plus Anti-TIGIT Monoclonal Antibody BGB-A1217 Versus Tislelizumab Plus Placebo as Second-Line Treatment in Patients With PD-L1 vCPS  10% Unresectable, Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma","primary_completion_date":"2023-11-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-03-31","last_update":"2021-08-09","description":"A study of tislelizumab (BGB-A317) plus ociperlimab versus tislelizumab plus placebo as second-line treatment in participants with programmed cell death protein-ligand 1 (PD-L1) visually estimated combined positive score (vCPS)  10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.","other_id":"BGB-A317-A1217-203","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          1. Histologically confirmed diagnosis of (esophageal squamous cell carcinoma) ESCC.\r\n\r\n          2. Have PD during or after first-line of systemic treatment for unresectable, locally\r\n             advanced, recurrent or metastatic ESCC.\r\n\r\n          3. Have measurable disease as assessed by RECIST v1.1.\r\n\r\n          4. Have confirmed PD-L1 vCPS  10% in tumor tissues tested by the central lab.\r\n\r\n          5. Eastern Cooperative Oncology Group Performance Status score of 0 or 1.\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, T-cell immunoreceptor with\r\n             immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains, or any\r\n             other antibody or drug specifically targeting T-cell costimulation or checkpoint\r\n             pathways.\r\n\r\n          2. Participants with evidence of fistula (either esophageal/bronchial or\r\n             esophageal/aorta).\r\n\r\n          3. Evidence of complete esophageal obstruction not amenable to treatment.\r\n\r\n          4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent\r\n             drainage (recurrence within 2 weeks after intervention).\r\n\r\n          5. Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin,\r\n             etc) or any investigational therapies within 14 days or 5 half-lives (whichever is\r\n             longer) before the first dose of study drug. Or has received palliative radiation\r\n             treatment or other local regional therapies within 14 days before the first dose of\r\n             study drug.\r\n\r\n        Note: Other protocol defined Inclusion/Exclusion criteria may apply.\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Esophageal Squamous Cell Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Tislelizumab","description":"Tislelizumab is a monoclonal antibody formulated for intravenous injection."},{"intervention_type":"Drug","name":"Drug: Ociperlimab","description":"Ociperlimab is a monoclonal antibody formulated for intravenous injection."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Ociperlimab placebo injection is a sterile, preservative-free solution for infusion formulated in the same buffer as ociperlimab active drug."}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) Assessed By The Investigator's Review Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1","time_frame":"Approximately 17 months","description":"The objective response rate will be defined as the proportion of participants who have complete response or partial response."},{"outcome_type":"primary","measure":"Overall Survival","time_frame":"Approximately 32 months","description":"Overall survival will be defined as the time from the date of randomization until the date of death due to any cause in all randomized participants."},{"outcome_type":"secondary","measure":"Progression-free Survival Assessed By The IRC And The Investigator Per RECIST v1.1","time_frame":"Approximately 32 months","description":"Progression-free survival will be defined as the time from the date of randomization to the date of first documentation of PD assessed by both the IRC and the investigator per RECIST v1.1 or death, whichever occurs first."},{"outcome_type":"secondary","measure":"Duration Of Response Assessed By The IRC And The Investigator Per RECIST v1.1","time_frame":"Approximately 32 months","description":"Duration of response will be defined as the time from the first determination of an objective response until the first documentation of PD as assessed by both the IRC and the investigator per RECIST v1.1, or death, whichever comes first."},{"outcome_type":"secondary","measure":"Disease Control Rate Assessed By The IRC And The Investigator Per RECIST v1.1","time_frame":"Approximately 32 months","description":"Disease Control Rate will be defined as the proportion of participants who have CR, PR, and stable disease assessed by both the IRC and the investigator per RECIST v1."},{"outcome_type":"secondary","measure":"Clinical Benefit Rate","time_frame":"Approximately 32 months","description":"The clinical benefit rate will be defined as the proportion of participants who achieve complete response, partial response, and durable stable disease (stable disease ≥ 24 weeks)."},{"outcome_type":"secondary","measure":"Health -related Quality Of Life (HRQoL): European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)","time_frame":"30 days (±7) after last dose","description":"The HRQoL will be assessed by scores in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-30) :"},{"outcome_type":"secondary","measure":"HRQoL: Dysphagia, Eating, Reflux and Pain Scales of EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18)","time_frame":"30 days (±7) after last dose","description":"The HRQoL will be assessed by scores in the EORTC QLQ-OES18."},{"outcome_type":"secondary","measure":"Incidence of Adverse Events And Serious Adverse Events","time_frame":"90 days (±14) after last dose"}]}
{"nct_id":"NCT04484142","start_date":"2021-03-30","phase":"Phase 2","enrollment":150,"brief_title":"Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)","official_title":"Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum Based Chemotherapy (TROPION-Lung05)","primary_completion_date":"2023-03-07","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-05-09","last_update":"2021-08-30","description":"This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.","other_id":"DS1062-A-U202","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Participants eligible for inclusion in the study must meet all inclusion criteria for this\r\n        study.\r\n\r\n          -  Sign and date the inform consent form (ICF) prior to the start of any study- specific\r\n             qualification procedures.\r\n\r\n          -  Adults 18 years (if the legal age of consent is >18 years old, then follow local\r\n             regulatory requirements)\r\n\r\n          -  Has pathologically documented NSCLC that:\r\n\r\n               1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based\r\n                  on the American Joint Committee on Cancer, Eighth Edition).\r\n\r\n               2. Has one or more of the following documented activating genomic alterations: EGFR,\r\n                  ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.\r\n\r\n        KRAS mutations in the absence of any of the genomic alterations specified above will be\r\n        excluded.\r\n\r\n        Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for\r\n        enrollment.\r\n\r\n        Participants who have not received osimertinib should be evaluated for the presence of EGFR\r\n        T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase\r\n        inhibitor (TKI), unless the participant is already known to be positive with document\r\n        results for this mutation or unless osimertinib is not locally approved.\r\n\r\n          -  Has documentation of radiographic disease progression while on or after receiving the\r\n             most recent treatment regimen for advanced or metastatic NSCLC.\r\n\r\n          -  Participant must meet the following for advanced or metastatic NSCLC:\r\n\r\n               1. Has been treated with at least one but no more than two cytotoxic\r\n                  agent-containing therapy in the metastatic setting:\r\n\r\n                    -  One platinum-containing regimen (either as monotherapy or combination\r\n                       therapy).\r\n\r\n                    -  May have received up to one additional line of cytotoxic agent-containing\r\n                       therapy.\r\n\r\n                    -  Those who received a platinum-containing regimen as adjuvant therapy for\r\n                       early stage disease must have relapsed or progressed while on the treatment\r\n                       or within 6 months of the last dose OR received at least one additional\r\n                       course of platinum-containing therapy (which may or may not be same as in\r\n                       the adjuvant setting) for relapsed/progressive disease.\r\n\r\n               2. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be\r\n                  in combination with a cytotoxic agent as part of a regimen described above or as\r\n                  an additional CPI regimen without a cytotoxic agent).\r\n\r\n               3. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally\r\n                  approved for the participant's applicable genomic alteration at the time of\r\n                  screening:\r\n\r\n                    -  Those who received a targeted agent for the applicable genomic alterations\r\n                       in the study as adjuvant therapy for early stage disease must have relapsed\r\n                       or progressed while on the treatment or within 6 months of the last dose OR\r\n                       received at least one additional course of targeted therapy for the same\r\n                       genomic alterations (which may or may not be same agent used in the adjuvant\r\n                       setting) for relapsed/progressive disease.\r\n\r\n                    -  Participants who have been treated with a prior TKI must receive additional\r\n                       targeted therapy, if clinically appropriate, for the genomic alterations\r\n                       that are considered amenable or the participant will not be allowed in the\r\n                       study.\r\n\r\n          -  Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor\r\n             biopsy that was recently collected (within 3 months of screening) after completion of\r\n             the most recent anticancer treatment regimen and that has a minimum of 10  4 micron\r\n             sections or a tissue block equivalent of 10  4 micron sections may be substituted for\r\n             the mandatory biopsy collected during screening.\r\n\r\n          -  Measurable disease based on local imaging assessment using RECIST v1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Participants meeting any exclusion criteria for this study will be excluded from this\r\n        study.\r\n\r\n          -  Has spinal cord compression or clinically active central nervous system metastases,\r\n             defined as untreated and symptomatic, or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms. Participants with clinically inactive\r\n             brain metastases may be included in the study.\r\n\r\n          -  Has leptomeningeal carcinomatosis.\r\n\r\n          -  Has prior treatment with:\r\n\r\n               1. Any chemotherapeutic agent targeting topoisomerase I, including antibody drug\r\n                  conjugate (ADC) containing such agent.\r\n\r\n               2. TROP2-targeted therapy.\r\n\r\n          -  Uncontrolled or significant cardiovascular disease:\r\n\r\n               1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.\r\n\r\n               2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.\r\n\r\n               3. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II\r\n                  to IV) at screening. Participants with a history of Class II to IV CHF prior to\r\n                  screening must have returned to Class I CHF and have LVEF 50% (by either an ECHO\r\n                  or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.\r\n\r\n               4. History of serious cardiac arrhythmia requiring treatment.\r\n\r\n               5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.\r\n\r\n               6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic\r\n                  blood pressure >110 mmHg).\r\n\r\n          -  Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that\r\n             required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis\r\n             cannot be ruled out by imaging at screening.\r\n\r\n          -  Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses\r\n\r\n          -  Clinically significant corneal disease.\r\n\r\n          -  Has other primary malignancies, except adequately resected non-melanoma skin cancer,\r\n             curatively treated in situ disease, or other solid tumors curatively treated, with no\r\n             evidence of disease for 3 years.\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: DS-1062a","description":"DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) As Assessed by Blind Independent Central Review Per RECIST v1.1 Following DS-1062a Intravenous Infusion","time_frame":"From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months","description":"ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous Infusion","time_frame":"From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months","description":"DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous (IV) Infusion","time_frame":"From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months","description":"PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of progressive disease or death due to any cause."},{"outcome_type":"secondary","measure":"Overall Survival (OS) Following DS-1062a Intravenous Infusion","time_frame":"From baseline until death due to any cause, up to approximately 23 months","description":"OS is defined as the time from the start of study treatment to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Intravenous Infusion in Participants with Advanced or Metastatic NSCLC with Actionable Genomic Alterations","time_frame":"From baseline up to approximately 23 months post treatment","description":"Reported treatment-emergent adverse events, serious adverse events, adverse events of interest, and those considered related to the study drug or study procedures, or that associated DS-1062a reduction, interruption, or discontinuation."},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a","time_frame":"Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a","time_frame":"Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a","time_frame":"Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)","description":"AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for DS-1062, total Anti-TROP2 antibody, and MAAA-1181a."}]}
{"nct_id":"NCT04849273","start_date":"2021-03-29","phase":"Phase 1/Phase 2","enrollment":210,"brief_title":"A Study of TPX-0131, a Novel Oral ALK Tyrosine Kinase Inhibitor, in Patients With ALK+ Advanced or Metastatic NSCLC","official_title":"A Phase 1/2 Study of TPX-0131, A Novel Oral ALK Tyrosine Kinase Inhibitor in Subjects With ALK+ Advanced or Metastatic NSCLC","primary_completion_date":"2025-04-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-08-31","last_update":"2021-08-13","description":"A phase 1/2, first-in-human, open-label study to evaluate the safety, tolerability, PK, and efficacy of the novel ALK inhibitor TPX-0131 in pretreated subjects with ALK+ advanced or metastatic non-small cell lung cancer (NSCLC). The study consists of two portions: 1) Phase 1 dose escalation, and 2) Phase 2 efficacy evaluation.","other_id":"TPX-0131-01","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Age  18 (or as required by local regulation).\r\n\r\n          -  Histological or cytological confirmation of advanced/metastatic ALK+ NSCLC.\r\n\r\n          -  Pretreated with up to three prior lines of an ALK TKI treatment, including at least\r\n             one prior line of a second or third-generation ALK TKI (alectinib, brigatinib,\r\n             ensartinib, or lorlatinib) in Phase 1.\r\n\r\n          -  ECOG performance status  1.\r\n\r\n          -  Existence of measurable or evaluable disease (according to Response evaluation\r\n             criteria in solid tumors [RECIST v1.1] criteria).\r\n\r\n          -  Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal\r\n             carcinomatosis are eligible.\r\n\r\n          -  Adequate organ function.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Major surgery within four weeks of the start of TPX-0131 treatment.\r\n\r\n          -  Clinically significant cardiovascular disease\r\n\r\n          -  Any of the following cardiac criteria:\r\n\r\n               -  Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and\r\n                  any factors that increase the risk of QTc prolongation or arrhythmic events\r\n\r\n               -  Any clinically important abnormalities in rhythm, conduction, or morphology of\r\n                  resting ECG\r\n\r\n          -  Known clinically significant active infections not controlled with systemic treatment\r\n             (bacterial, fungal, viral including HIV positivity).\r\n\r\n          -  Gastrointestinal disease or other malabsorption syndromes that would impact drug\r\n             absorption.\r\n\r\n          -  Subjects being treated with or anticipating the need for treatment with strong CYP3A4\r\n             inhibitors or inducers.\r\n\r\n          -  Subjects with current or anticipated need for drugs that are sensitive CYP2C9\r\n             substrates with narrow therapeutic indices.\r\n      ","sponsor":"Turning Point Therapeutics, Inc.","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer|Non-Small Cell Lung Cancer|NSCLC|Advanced Solid Tumor|Metastatic Solid Tumor|ALK Gene Mutation","interventions":[{"intervention_type":"Drug","name":"Drug: TPX-0131","description":"Oral TPX-0131 tablets"}],"outcomes":[{"outcome_type":"secondary","measure":"AUC (area under plasma concentration time curve) of TPX-0131","time_frame":"Up to 120 hours post-dose","description":"Determine the AUC of TPX-0131"},{"outcome_type":"secondary","measure":"Cmax (maximum plasma concentration) of TPX-0131","time_frame":"Up to 120 hours post-dose","description":"Evaluate the maximum plasma concentration of TPX-0131"},{"outcome_type":"primary","measure":"Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0131","time_frame":"Within 28 days of the first TPX-0131 dose for each patient","description":"Evaluate the safety and tolerability of TPX-0131"},{"outcome_type":"primary","measure":"Define the Recommended Phase 2 Dose","time_frame":"Approximately 22 months","description":"Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of TPX-0131"},{"outcome_type":"primary","measure":"Define the objective response rate (ORR)","time_frame":"Approximately 44 months","description":"Determine the preliminary efficacy by the ORR in defined cohorts with ALK+ advanced or metastatic NSCLC"},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Approximately 44 months","description":"Determine the DOR of TPX-0131"},{"outcome_type":"secondary","measure":"Time to response (TTR)","time_frame":"Approximately 44 months","description":"Determine the TTR of TPX-0131"},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR)","time_frame":"Approximately 44 months","description":"Determine the CBR of TPX-0131"},{"outcome_type":"secondary","measure":"Intracranial tumor response","time_frame":"Approximately 44 months","description":"Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"Approximately 44 months","description":"Determine the PFS of TPX-0131"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Approximately 44 months","description":"Determine the efficacy and safety of TPX-0131"},{"outcome_type":"secondary","measure":"Adverse events (AEs)","time_frame":"Approximately 44 months","description":"Evaluate the overall safety profile of TPX-0131"},{"outcome_type":"secondary","measure":"CNS Progression-Free Survival (CNS-PFS)","time_frame":"Approximately 44 months","description":"Determine the CNS-PFS in patients with measurable brain metastases using Modified RECIST v1.1"},{"outcome_type":"secondary","measure":"Patient-reported quality of life - Core Quality of Life Questionnaire","time_frame":"Approximately 44 months","description":"Estimate the effect of TPX-0131 on patient-reported outcomes using the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire to assess subject's ability to complete 30 daily activities. The scale, from 1 to 4 (1 = not difficult to 4 = very difficult), indicates the level of difficulty to complete a task."},{"outcome_type":"secondary","measure":"Patient-reported quality of life - Lung Cancer Quality of Life Questionnaire","time_frame":"Approximately 44 months","description":"Estimate the effect of TPX-0131 on patient-reported outcomes, using the Lung Cancer Quality of Life Questionnaire asks questions related to 13 specific lung cancer symptoms. The scale, from 1 to 4\r\n(1 = not often to 4 = very often), indicates the frequency of symptoms experienced in a given week."}]}
{"nct_id":"NCT04776148","start_date":"2021-03-29","phase":"Phase 3","enrollment":434,"brief_title":"Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)","official_title":"A Phase 3 Randomized Study of Lenvatinib in Combination With Pembrolizumab Versus Standard of Care in Participants With Metastatic Colorectal Cancer Who Have Received and Progressed On or After or Became Intolerant to Prior Treatment","primary_completion_date":"2023-11-22","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-11-22","last_update":"2021-09-16","description":"The purpose of this study is to assess the safety and efficacy of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in participants with metastatic colorectal cancer. The study will also compare lenvatinib plus pembrolizumab with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil hydrochloride). The primary study hypothesis is that lenvatinib plus pembrolizumab is superior to standard of care with respect to overall survival.","other_id":"7902-017","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has histologically or cytologically confirmed diagnosis of unresectable and metastatic\r\n             colorectal adenocarcinoma (Stage IV A, B and C as defined by American Joint Committee\r\n             on Cancer [AJCC] 8th edition). Note: Tumor must be determined to be NOT microsatellite\r\n             instability-high (MSI-H)/mismatch repair deficient (dMMR) by local testing\r\n\r\n          -  Has been previously treated for their disease and has shown disease progression as\r\n             defined by RECIST 1.1 on or after or could not tolerate standard treatment, which must\r\n             include ALL of the following agents if approved and locally available in the country\r\n             where the participant is randomized:\r\n\r\n               1. fluoropyrimidine, irinotecan and oxaliplatin\r\n\r\n               2. with or without an anti-vascular endothelial growth factor (VEGF) monoclonal\r\n                  antibody (bevacizumab)\r\n\r\n               3. with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies\r\n                  (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants\r\n\r\n               4. BRAF inhibitor (in combination with cetuximab +/- binimetinib) for BRAF V600E\r\n                  mutated metastatic colon cancer (mCRC)\r\n\r\n          -  Has measurable disease per RECIST 1.1 assessed by the investigator\r\n\r\n          -  Has provided to a designated central laboratory an archival tumor tissue sample or\r\n             newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not\r\n             been previously irradiated\r\n\r\n          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3\r\n             days prior to randomization\r\n\r\n          -  Has a life expectancy of at least 3 months, based on the investigator assessment\r\n\r\n          -  Has the ability to swallow capsules or ingest a suspension orally or by a feeding tube\r\n\r\n          -  Has adequately controlled blood pressure (BP) with or without antihypertensive\r\n             medications, defined as BP 150/90 millimeter of mercury (mmHg) with no change in\r\n             antihypertensive medications within 1 week prior to randomization\r\n\r\n          -  Male participants must agree to the following during the treatment period and for at\r\n             least 90 days after the last dose of regorafenib or TAS-102 and at least 7 days after\r\n             the last dose of lenvatinib: refrain from donating sperm PLUS either be abstinent from\r\n             heterosexual intercourse as their preferred and usual lifestyle or use contraception.\r\n             The male contraception period should continue for at least 7 days after\r\n             discontinuation of lenvatinib\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant or\r\n             breastfeeding, and at least one of the following conditions applies: is not a woman of\r\n             childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective\r\n             contraceptive method during the treatment period and for at least 30 days after the\r\n             last dose of lenvatinib, 120 days after the last dose of pembrolizumab, and 180 days\r\n             after the last dose of regorafenib or TAS-102 (whichever is last) AND agrees not to\r\n             donate eggs (ova, oocytes)\r\n\r\n          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within\r\n             24 hours before the first dose of study treatment\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has a tumor that is microsatellite instability-high (MSI-H)/mismatch repair deficient\r\n             (dMMR) per local testing\r\n\r\n          -  Has presence of gastrointestinal condition, eg, malabsorption, that might affect the\r\n             absorption of study drug.\r\n\r\n          -  Has present or progressive accumulation of pleural, ascitic, or pericardial fluid\r\n             requiring drainage or diuretic drugs within 2 weeks prior to enrollment\r\n\r\n          -  Has radiographic evidence of encasement or invasion of a major blood vessel invasion\r\n             or of intratumoral cavitation. In the chest, major blood vessels include the main\r\n             pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins,\r\n             the superior or inferior vena cava, and the aorta\r\n\r\n          -  Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the\r\n             first dose of study drug\r\n\r\n          -  Has clinically significant cardiovascular disease within 12 months from first dose of\r\n             study intervention, including New York Heart Association Class III or IV congestive\r\n             heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or\r\n             cardiac arrhythmia associated with hemodynamic instability.\r\n\r\n        Participants with cardiac failure NYHA Class II, III and IV are not allowed to be assigned\r\n        to the regorafenib in Arm B\r\n\r\n          -  Has a history of arterial thromboembolism within 12 months of start of study drug\r\n\r\n          -  Has urine protein 1 gram/24 hour\r\n\r\n          -  Has prolongation of QT interval corrected with Fridericia's formula (QTcF interval) to\r\n             >480 milliseconds\r\n\r\n          -  Has left ventricular ejection fraction (LVEF) below the institutional (or local\r\n             laboratory) normal range as determined by multigated acquisition (MUGA) or\r\n             echocardiogram (ECHO)\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years with certain exceptions\r\n\r\n          -  Has serious nonhealing wound, ulcer or bone fracture\r\n\r\n          -  Has had major surgery within 3 weeks prior to first dose of study treatment\r\n\r\n          -  Has received biologic response modifiers (eg, granulocyte colony-stimulating factor)\r\n             within 4 weeks before study entry\r\n\r\n          -  Has preexisting Grade 3 gastrointestinal or nongastrointestinal fistula\r\n\r\n          -  Has received prior treatment with a combination of an anti-PD-1, anti-PD-L1, or anti\r\n             PD-L2 agent with anti-VEGF monoclonal antibodies or vascular endothelial growth factor\r\n             receptor (VEGFR) inhibitors\r\n\r\n          -  Has previously received regorafenib or TAS-102\r\n\r\n          -  Has received prior systemic anti-cancer therapy including investigational agents\r\n             within 28 days prior to randomization\r\n\r\n          -  Has received prior radiotherapy within 2 weeks of start of study treatment\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days prior to the first dose\r\n             of study treatment\r\n\r\n          -  Has known intolerance to lenvatinib, regorafenib, or TAS-102 and/or any of their\r\n             excipients\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 28 days prior to the first dose of\r\n             study treatment\r\n\r\n          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.\r\n\r\n          -  Has severe hypersensitivity (Grade 3) to pembrolizumab and/or any of its excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior the first dose of study medication\r\n\r\n          -  Has a history of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis\r\n\r\n          -  Has an active infection requiring systemic therapy\r\n\r\n          -  Has a known history of Human Immunodeficiency Virus (HIV) infection\r\n\r\n          -  Has a known history of Hepatitis B or known active Hepatitis C virus infection\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the study, interfere with the participant's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             the participant to participate, in the opinion of the treating investigator\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with the\r\n             participant's ability to cooperate with the requirements of the study\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Colorectal Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: pembrolizumab","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: lenvatinib","description":"oral capsule"},{"intervention_type":"Drug","name":"Drug: regorafenib","description":"oral tablet"},{"intervention_type":"Drug","name":"Drug: TAS-102 (trifluridine and tipiracil)","description":"oral tablet"}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 40 months","description":"OS is defined as the time from randomization to the time of death from any cause. OS will be presented."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)","time_frame":"Up to approximately 40 months","description":"PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. PFS as assessed per modified RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)","time_frame":"Up to approximately 40 months","description":"ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR as assessed per modified RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)","time_frame":"Up to approximately 40 months","description":"For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed per modified RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experience an Adverse Event (AE)","time_frame":"Up to approximately 40 months","description":"An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience one or more adverse events will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)","time_frame":"Up to approximately 40 months","description":"An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an adverse event will be presented."},{"outcome_type":"secondary","measure":"Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score","time_frame":"Baseline and up to approximately 24 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; \"How would you rate your overall health during the past week?\") and Quality of Life (QoL; \"How would you rate your overall quality of life during the past week?\") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome."},{"outcome_type":"secondary","measure":"Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1-5) Score","time_frame":"Baseline and up to approximately 24 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function."},{"outcome_type":"secondary","measure":"Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Appetite Loss (Item 13) Score","time_frame":"Baseline and up to approximately 24 months","description":"The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question \"Have you lacked appetite?\" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score will be presented."},{"outcome_type":"secondary","measure":"Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score","time_frame":"Baseline and up to approximately 24 months","description":"The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question \"Did you have a bloated feeling in your abdomen?\" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score will be presented."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score","time_frame":"Up to approximately 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1-5) Score","time_frame":"Up to approximately 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Appetite Loss (Item 13) Score","time_frame":"Up to approximately 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in appetite loss (QLQ-C30 Item 13) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in appetite loss score, will be presented. A longer TTD indicates a better outcome."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score","time_frame":"Up to approximately 24 months","description":"TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in bloating (QLQ-CR29 Item 37) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in appetite loss score, will be presented. A longer TTD indicates a better outcome."}]}
{"nct_id":"NCT04714190","start_date":"2021-03-24","phase":"Phase 3","enrollment":351,"brief_title":"A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer With the HER2-Overexpression","official_title":"Randomized, Controlled, Multicenter Phase III Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of Locally Advanced or Metastatic Gastric Cancer With HER2-overexpression","primary_completion_date":"2022-07-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-31","last_update":"2021-04-27","description":"This is a Phase III, randomized, multicenter, open-label clinical trial designed to compare RC48-ADC to physician choice standard treatment in participants with human epidermal growth factor receptor 2 (HER2)-overexpression locally advanced or metastatic gastric cancer.","other_id":"RC48-007","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Voluntary agreement to provide written informed consent.\r\n\r\n          -  Male or female, Age  18 years.\r\n\r\n          -  Predicted survival  12 weeks.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.\r\n\r\n          -  All female subjects will be considered to be of child-bearing potential unless they\r\n             are postmenopausal, or have been sterilized surgically.Female subjects of\r\n             child-bearing potential must agree to use two forms of highly effective contraception.\r\n             Male subjects and their female partner who are of child-bearing potential must agree\r\n             to use two forms of highly effective contraception.\r\n\r\n          -  Willing to adhere to the study visit schedule and the prohibitions and restrictions\r\n             specified in this protocol.\r\n\r\n          -  Adequate organ function.\r\n\r\n          -  All subjects must have inoperable, advanced or metastatic gastric or or\r\n             gastroesophageal adenocarcinoma\r\n\r\n          -  Have had progression or intolerance following receipt of at least two systemic\r\n             chemotherapy for advanced or metastatic disease.\r\n\r\n          -  HER2 overexpression defined as HER2 IHC 2+ or 3+.\r\n\r\n          -  According to the RECIST 1.1 standard, there is at least one measurable lesion.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known hypersensitivity to Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE\r\n             Conjugate For Injection.\r\n\r\n          -  History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to\r\n             trial treatment.\r\n\r\n          -  History of major surgery within 4 weeks of planned start of trial treatment.\r\n\r\n          -  Has received a live virus vaccine within 4 weeks of planned start of trial treatment.\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the trial, interfere with the subject's\r\n             participation for the full duration of the trial, or is not in the best interest of\r\n             the subject to participate, in the opinion of the treating investigator.\r\n\r\n          -  History of other malignancy within the previous 5 years, except for appropriately\r\n             treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with\r\n             a similar curative outcome as those mentioned above.\r\n\r\n          -  Assessed by the investigator to be unable or unwilling to comply with the requirements\r\n             of the protocol.\r\n      ","sponsor":"RemeGen Co., Ltd.","sponsor_type":"Industry","conditions":"Gastric Cancer|HER2 Overexpressing Gastric Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: RC48-ADC","description":"2.5 mg/kg IV every 2 weeks"},{"intervention_type":"Drug","name":"Drug: Paclitaxel injection","description":"Administered according to label, as one option for Physician's Choice (determined before randomization)"},{"intervention_type":"Drug","name":"Drug: Irinotecan Hydrochloride Injection","description":"Administered according to label, as one option for Physician's Choice (determined before randomization)"}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival (OS)","time_frame":"within approximately 3 years","description":"Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS), evaluated by the investigator","time_frame":"within approximately 3 years","description":"Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard."},{"outcome_type":"secondary","measure":"Objective remission rate (ORR)","time_frame":"within approximately 3 years","description":"The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed)."},{"outcome_type":"secondary","measure":"Duration of relief (DOR)","time_frame":"within approximately 3 years","description":"DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"within approximately 3 years","description":"Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study."},{"outcome_type":"secondary","measure":"Tumor progression time (TTP)","time_frame":"within approximately 3 years","description":"Time to disease progression (TTP) refers to the time from the random date to the first disease progression (calculated by the event that occurred first). Disease progression will be evaluated by the investigator according to the RECIST 1.1 standard (investigator and Independent Review Committee(IRC) evaluation)."}]}
{"nct_id":"NCT04817007","start_date":"2021-03-23","phase":"Phase 1","enrollment":156,"brief_title":"A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)","official_title":"A Phase 1b Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis","primary_completion_date":"2023-11-03","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-08-09","last_update":"2021-09-17","description":"The purpose of this study is to assess the safety, tolerability, and efficacy of BMS-986158 alone and in combination with either Ruxolitinib or Fedratinib in participants with Dynamic International Prognostic Scoring System (DIPSS)-intermediate or high risk blood cancer. Part 1 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and Part 2 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and BMS-986158 alone.","other_id":"CA011-023","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Diagnosis of primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or\r\n             post-polycythemia vera (PV) myelofibrosis\r\n\r\n          -  Treatment-related toxicities from prior therapy resolved to Grade 1 or pre-treatment\r\n             baseline or determined to be irreversible prior to study treatment\r\n\r\n          -  Must agree to follow specific methods of contraception, if applicable\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Women who are pregnant or breastfeeding at screening\r\n\r\n          -  Any significant acute or uncontrolled chronic medical illness\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Myelofibrosis","interventions":[{"intervention_type":"Drug","name":"Drug: BMS-986158","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Ruxolitinib","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Fedratinib","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of adverse events (AEs)","time_frame":"Up to 52 months"},{"outcome_type":"primary","measure":"Incidence of serious adverse events (SAEs)","time_frame":"Up to 52 months"},{"outcome_type":"primary","measure":"Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria","time_frame":"Up to 26 months"},{"outcome_type":"primary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 52 months"},{"outcome_type":"primary","measure":"Incidence of death","time_frame":"Up to 52 months"},{"outcome_type":"secondary","measure":"Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to 52 months"},{"outcome_type":"secondary","measure":"Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated) assessed by BICR","time_frame":"Up to 52 months"},{"outcome_type":"secondary","measure":"Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF)","time_frame":"Up to 168 days"},{"outcome_type":"secondary","measure":"Additional measures based on TSS measured by MFSAF","time_frame":"Up to 168 days"},{"outcome_type":"secondary","measure":"For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline","time_frame":"Up to 24 months"},{"outcome_type":"secondary","measure":"For transfusion dependent (TD), proportion of participants becoming TI as measured by the absence of red blood cell (RBC) transfusions over any consecutive 12-week period","time_frame":"Up to 24 months"},{"outcome_type":"secondary","measure":"Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax)","time_frame":"Up to 56 days"},{"outcome_type":"secondary","measure":"Summary of PK parameters: time of maximum observed concentration (Tmax)","time_frame":"Up to 56 days"},{"outcome_type":"secondary","measure":"Summary of PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T))","time_frame":"Up to 56 days"},{"outcome_type":"secondary","measure":"Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: SDPFS rates at 6 months and 12 months","time_frame":"6 month and 12 month","description":"International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)\r\nSpleen and disease progression free survival (SDPFS)"},{"outcome_type":"secondary","measure":"Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: median SDPFS at 6 months and 12 months","time_frame":"6 month and 12 month"}]}
{"nct_id":"NCT04499924","start_date":"2021-03-22","phase":"Phase 2/Phase 3","enrollment":578,"brief_title":"Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer","official_title":"A Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously Treated, Locally-advanced Unresectable or Metastatic HER2+ Gastric or Gastroesophageal Junction Adenocarcinoma (GEC)","primary_completion_date":"2025-05-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-03-31","last_update":"2021-09-16","description":"This study is being done to see if tucatinib with trastuzumab, ramucirumab and paclitaxel works better than ramucirumab and paclitaxel to treat HER2-positive (HER2+) cancer of the gut (stomach or gastroesophageal cancer). This study will also look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. Study treatment will be given in 28-day cycles. In the Phase 2 part of the trial, participants and their doctors will know what drugs are being given (open-label). In the Phase 3 part, the study is \"blinded.\" This means that participants, their doctor, and the study sponsor will not know which drugs are being given.","other_id":"SGNTUC-022","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of locally-advanced unresectable\r\n             or metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC)\r\n\r\n          -  HER2+ disease documented since progression of the most recent line of systemic\r\n             therapy, as follows:\r\n\r\n               -  Phase 2 paclitaxel dose optimization stage:\r\n\r\n                    -  HER2 amplification in a blood-based NGS assay performed at a central\r\n                       laboratory, or\r\n\r\n                    -  HER2 overexpression/amplification immunohistochemistry (IHC) and in situ\r\n                       hybridization (ISH) (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample\r\n\r\n               -  Phase 2 dose expansion stage:\r\n\r\n                    -  Cohort 2A: HER2 amplification in a blood-based NGS assay performed at a\r\n                       central laboratory\r\n\r\n                    -  Cohort 2B: No HER2 amplification by blood-based NGS assay, but HER2\r\n                       overexpression/amplification by IHC and ISH (IHC3+ or IHC2+/ISH+) assay of a\r\n                       tumor tissue sample\r\n\r\n               -  Phase 3: HER2 amplification in a blood-based NGS assay performed at a central\r\n                  laboratory\r\n\r\n          -  History of prior treatment with a HER2-directed antibody\r\n\r\n          -  Progressive disease during or after first-line therapy for locally-advanced\r\n             unresectable or metastatic GEC\r\n\r\n          -  Phase 2: Measurable disease according to RECIST version 1.1\r\n\r\n          -  Phase 3: Measurable or non-measurable disease according to RECIST version 1.1\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\r\n\r\n          -  Life expectancy of at least 3 months, in the opinion of the investigator\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Subjects with squamous cell or undifferentiated GEC\r\n\r\n          -  Having received more than 1 line of prior systemic therapy for locally-advanced\r\n             unresectable or metastatic disease\r\n\r\n          -  Having received taxanes 12 months prior to enrollment, prior treatment with\r\n             ramucirumab, or prior treatment with tucatinib, lapatinib, neratinib, afatinib, or any\r\n             other investigational anti-HER2 and/or anti-EGFR tyrosine kinase inhibitor, or with\r\n             T-DM1, T-Dxd, or any other HER2-directed antibody-drug conjugate\r\n\r\n          -  Phase 2 paclitaxel dose optimization stage only: history of prior partial or total\r\n             gastrectomy\r\n\r\n          -  Unable to swallow pills\r\n      ","sponsor":"Seagen Inc.","sponsor_type":"Industry","conditions":"Gastric Adenocarcinoma|Gastroesophageal Junction Adenocarcinoma|Esophageal Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: tucatinib","description":"300 mg given twice daily orally"},{"intervention_type":"Drug","name":"Drug: trastuzumab","description":"6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter"},{"intervention_type":"Drug","name":"Drug: ramucirumab","description":"8 mg/kg will be administered IV on Days 1 and 15 of each cycle"},{"intervention_type":"Drug","name":"Drug: paclitaxel","description":"60 or 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle"},{"intervention_type":"Other","name":"Other: tucatinib placebo","description":"Given twice daily orally"},{"intervention_type":"Other","name":"Other: trastuzumab placebo","description":"IV on Days 1 and 15 of each cycle"}],"outcomes":[{"outcome_type":"secondary","measure":"Trough concentration (Ctrough) of tucatinib (Phase 2 only)","time_frame":"18 months","description":"PK parameter"},{"outcome_type":"secondary","measure":"Ctrough of paclitaxel (Phase 2 only)","time_frame":"18 months","description":"PK parameter"},{"outcome_type":"secondary","measure":"Incidence of dose modifications (Phase 3 only)","time_frame":"36 months"},{"outcome_type":"primary","measure":"Overall survival (OS) (Phase 3 only)","time_frame":"60 months","description":"OS is defined as the time from randomization to death due to any cause"},{"outcome_type":"primary","measure":"Progression-free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) version 1.1 according to investigator assessment (Phase 3 only)","time_frame":"36 months","description":"PFS is defined as the time from randomization to the date of disease progression or death from any cause"},{"outcome_type":"primary","measure":"Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)","time_frame":"During first cycle of treatment; up to one month"},{"outcome_type":"primary","measure":"Incidence of adverse events (AEs) (Phase 2 only)","time_frame":"18 months","description":"An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment."},{"outcome_type":"primary","measure":"Incidence of laboratory abnormalities (Phase 2 only)","time_frame":"18 months","description":"To be summarized using descriptive statistics."},{"outcome_type":"primary","measure":"Incidence of dose modifications (Phase 2 only)","time_frame":"18 months"},{"outcome_type":"secondary","measure":"Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)","time_frame":"36 months","description":"ORR is defined as the proportion of subjects with best overall response of CR or PR"},{"outcome_type":"secondary","measure":"ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)","time_frame":"36 months","description":"ORR is defined as the proportion of subjects with best overall response of CR or PR"},{"outcome_type":"secondary","measure":"Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)","time_frame":"36 months","description":"DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)","time_frame":"36 months","description":"DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)"},{"outcome_type":"secondary","measure":"PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)","time_frame":"36 months","description":"PFS is defined as the time from randomization to the date of disease progression or death from any cause"},{"outcome_type":"secondary","measure":"Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)","time_frame":"36 months","description":"ORR is defined as the proportion of subjects with best overall response of CR or PR"},{"outcome_type":"secondary","measure":"ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)","time_frame":"36 months","description":"ORR is defined as the proportion of subjects with best overall response of CR or PR"},{"outcome_type":"secondary","measure":"DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)","time_frame":"36 months","description":"DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause"},{"outcome_type":"secondary","measure":"DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)","time_frame":"36 months","description":"DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)"},{"outcome_type":"secondary","measure":"Incidence of AEs (Phase 3 only)","time_frame":"36 months","description":"An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment."},{"outcome_type":"secondary","measure":"Incidence of laboratory abnormalities (Phase 3 only)","time_frame":"36 months","description":"To be summarized using descriptive statistics."},{"outcome_type":"secondary","measure":"PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)","time_frame":"18 months","description":"PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause"},{"outcome_type":"secondary","measure":"Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)","time_frame":"1 month","description":"Pharmacokinetic (PK) parameter"},{"outcome_type":"secondary","measure":"AUC to AUClast of paclitaxel (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Cmax of paclitaxel (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Time of Cmax (Tmax) of tucatinib (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Tmax of paclitaxel (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"MRAUC of paclitaxel (Phase 2 only)","time_frame":"1 month","description":"PK parameter"},{"outcome_type":"secondary","measure":"Time to deterioration of GEC symptoms as assessed by the European Organisation for Research and Treatment or Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and EORTC QLQ-OG25 questionnaires.","time_frame":"36 months","description":"The EORTC questionnaires measure aspects of health-related quality of life (HRQoL). Time to deterioration will be assessed in specific pre-specified single items from either the EORTC QLQ-C30 or EORTC QLQ OG25 and deterioration is defined as a 10-point increase from baseline in the symptom scales and a 10-point decrease from baseline for overall HRQoL."},{"outcome_type":"secondary","measure":"Change from baseline in health-related quality of life (HRQoL)","time_frame":"36 months"},{"outcome_type":"secondary","measure":"Utility index values as assessed by the EQ-5D-5L","time_frame":"36 months","description":"The EQ-5D-5L questionnaire is used as a preference based measurement of HRQoL outcomes. Data will be summarized using descriptive statistics."}]}
{"nct_id":"NCT04644237","start_date":"2021-03-19","phase":"Phase 2","enrollment":150,"brief_title":"Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)","official_title":"A Phase 2, Multicenter, Randomized Study of Trastuzumab Deruxtecan in Subjects With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (DESTINY-LUNG02)","primary_completion_date":"2023-03-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-09-30","last_update":"2021-07-12","description":"This study was designed to evaluate the safety and efficacy of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer (NSCLC) participants who had disease recurrence or progression during/after at least one regimen of prior anticancer therapy (second line or later) that must have contained a platinum-based chemotherapy drug.","other_id":"DS8201-A-U206","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Written informed consent\r\n\r\n          -  Men or women 18 years, follow local regulatory requirements if the legal age of the\r\n             consent for study participation is >18 years\r\n\r\n          -  Pathologically documented metastatic NSCLC with a known activating HER2 mutation.\r\n             Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for\r\n             enrollment.\r\n\r\n          -  Had previous treatment (second line or later [2L+], including platinum therapy), not\r\n             amenable to curative surgery or radiation\r\n\r\n          -  Presence of at least 1 measurable lesion confirmed by the blinded Independent Central\r\n             Review based on RECIST version 1.1\r\n\r\n          -  Willing and able to provide an archival tumor tissue sample. A fresh biopsy is\r\n             required if an archival tumor tissue sample cannot be supplied. Fine needle aspirates\r\n             are not acceptable.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status 0 to 1\r\n\r\n          -  Left ventricular ejection fraction  50% within 28 days before randomization\r\n\r\n          -  Adequate organ function as specified in protocol within 14 days before randomization\r\n\r\n          -  Adequate treatment washout period before randomization\r\n\r\n          -  Participants of reproductive/childbearing potential agree to use a highly effective\r\n             form of contraception (or avoid intercourse) during study period and up to 7 months\r\n             (females) and 4 months (males) after last study dose\r\n\r\n          -  Males should not freeze or donate sperm throughout the study period up to at least 4\r\n             months after last study dose; females should not donate or retrieve ova for their own\r\n             use throughout the study period and up to at least 7 months after last study dose\r\n\r\n          -  Life expectancy 3 months or more\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Known driver mutation in the epidermal growth factor receptor (EGFR) or BRAF gene or a\r\n             known anaplastic lymphoma kinase (ALK) or ROS1 fusion\r\n\r\n          -  Medical history of myocardial infarction within 6 months before randomization,\r\n             symptomatic congestive heart failure (CHF) (New York Heart Association Class II to\r\n             IV). Participants with troponin levels above upper limit of normal at screening (as\r\n             defined by the manufacturer) and without any myocardial infarction (MI)-related\r\n             symptoms should have a cardiologic consultation before enrollment to rule out MI\r\n\r\n          -  Corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males)\r\n             based on average of the triplicate12-lead electrocardiogram at screening\r\n\r\n          -  History of non-infectious interstitial lung disease (ILD)/pneumonitis that required\r\n             steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled\r\n             out by imaging at screening\r\n\r\n          -  Spinal cord compression or clinically active central nervous system metastases,\r\n             defined as untreated and symptomatic, or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms\r\n\r\n          -  Multiple primary malignancies within 3 years, except adequately resected non-melanoma\r\n             skin cancer, curatively treated in-situ disease, or other solid tumors curatively\r\n             treated\r\n\r\n          -  History of severe hypersensitivity reactions to either the drug substances or inactive\r\n             ingredients in the drug product\r\n\r\n          -  History of severe hypersensitivity reactions to other monoclonal antibodies\r\n\r\n          -  Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\r\n\r\n          -  Substance abuse or any other medical conditions such as clinically significant cardiac\r\n             or psychological conditions, that may, in the opinion of the investigator, interfere\r\n             with the participant's participation in the clinical study or evaluation of the\r\n             clinical study results\r\n\r\n          -  Known human immunodeficiency virus (HIV) infection\r\n\r\n          -  Known active, clinically relevant liver disease (eg, active hepatitis B, or active\r\n             hepatitis C), based on available blood tests, liver ultrasound, or liver biopsy\r\n             results\r\n\r\n          -  Unresolved toxicities from previous anticancer therapy, defined as toxicities (other\r\n             than alopecia) not yet resolved to Grade  1 or baseline\r\n\r\n          -  Pregnant, breastfeeding, or planning to become pregnant\r\n\r\n          -  Otherwise considered inappropriate for the study by the Investigator\r\n\r\n          -  Lung-specific intercurrent clinically significant illnesses including, but not limited\r\n             to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the\r\n             study randomization, severe asthma, severe COPD, restrictive lung disease, pleural\r\n             effusion, etc.)\r\n\r\n          -  Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid\r\n             arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of\r\n             pulmonary involvement at the time of screening\r\n\r\n          -  Prior complete pneumonectomy\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Non-Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab deruxtecan","description":"Trastuzumab deruxtecan 100 mg will be provided as a sterile lyophilized powder and reconstituted with 5 mL water for injection (final concentration 20 mg/mL [ie, 100 mg/5 mL]). The study drug will be administered as an intravenous (IV) infusion over 30 to 90 min Q3W  2 days. The initial dose of study drug will be infused for 90  10 min."}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), will be assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), will be assessed by the Investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Duration of response (DoR) is defined as the time from the initial response (complete response [CR] or partial response [PR]) until documented tumor progression or death from any cause. DoR is only defined for participants who achieved confirmed CR or PR. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Disease control rate (DCR) is the sum of complete response (CR), partial response (PR), and stable disease (SD) rates. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Progression-free survival (PFS) is defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on blinded independent central review (BICR) and investigator assessment."},{"outcome_type":"secondary","measure":"Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors","time_frame":"9 months after the last participant is randomized or later, up to approximately 31 months","description":"Overall survival (OS) is defined as the time from date of randomization until death from any cause."},{"outcome_type":"secondary","measure":"The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors","time_frame":"Baseline up to 40 days after last dose, up to approximately 31 months"},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a","time_frame":"Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a","time_frame":"Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a","time_frame":"Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Incidence of Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors","time_frame":"Pre-dose on Day 1 of Cycles 1, 2 and 4, and then every 4 cycles (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire for Lung Cancer Trials (QLQ-LC13) Scores","time_frame":"On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit","description":"The EORTC QLQ-C30 consists of 30 questions assessing global health-related quality of life, five aspects of subject functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher scores for functioning scales and global health status indicate a better level of functioning while higher scores on the symptom and single-item scales indicate a higher level of symptoms. The QLQ-LC13 is a 13-item questionnaire designed to assess lung cancer-related symptoms and treatment side effects. The scales ranges from 1=not at all to 4=very much. The summation of scores range from 0 to 100, where higher scores represent increasing symptoms levels.\r\nscales."},{"outcome_type":"secondary","measure":"Time to deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scores","time_frame":"On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit","description":"The EORTC QLQ-C30 consists of 30 questions assessing global health-related quality of life, five aspects of subject functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher scores for functioning scales and global health status indicate a better level of functioning while higher scores on the symptom and single-item scales indicate a higher level of symptoms."}]}
{"nct_id":"NCT04702880","start_date":"2021-03-17","phase":"Phase 2","enrollment":120,"brief_title":"A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer","official_title":"A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer","primary_completion_date":"2023-09-24","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-09-07","last_update":"2021-07-12","description":"The purpose of this study is to demonstrate that treatment with BMS-986012 in combination with carboplatin, etoposide, and nivolumab will have acceptable safety and tolerability and will improve progression-free survival compared with carboplatin, etoposide, and nivolumab alone in newly diagnosed participants with extensive-stage small cell lung cancer (ES-SCLC).","other_id":"CA001-050","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically documented extensive-stage small cell lung cancer\r\n             (ES-SCLC) and extensive-stage disease (American Joint Committee on Cancer, 7th\r\n             edition, Stage IV [T any, N any, M1a, or M1b], or T3-4 due to multiple lung nodules\r\n             that are too extensive or tumor or nodal volume that is too large to be encompassed in\r\n             a tolerable radiation plan)\r\n\r\n          -  Must provide a fresh tumor biopsy from the primary disease site (when possible) or\r\n             from any metastatic site when the primary site is not available\r\n\r\n          -  Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1\r\n\r\n          -  At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging\r\n             (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (Response\r\n             Evaluation Criteria in Solid Tumors (RECIST) v1.1) criteria\r\n\r\n          -  Adequate hematologic and end organ function\r\n\r\n          -  Must agree to follow specific methods of contraception, if applicable\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Women who are pregnant or breastfeeding\r\n\r\n          -  Prior chemotherapy, radiation therapy, or biologic therapy for small cell lung cancer\r\n             (SCLC) for first-line treatment\r\n\r\n          -  Symptomatic brain or other central nervous system (CNS) metastases\r\n\r\n          -  Paraneoplastic autoimmune syndrome requiring systemic treatment\r\n\r\n          -  History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic\r\n             pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening\r\n             chest CT scan\r\n\r\n          -  Grade  2 peripheral sensory neuropathy at study entry\r\n\r\n          -  Significant uncontrolled cardiovascular disease\r\n\r\n          -  Active, known or suspected autoimmune disease or inflammatory disorder\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Extensive-stage Small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Nivolumab","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Etoposide","description":"Specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: BMS-986012","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"secondary","measure":"Measures of tumor fucosyl-GM1 (fuc-GM1) expression by immunohistochemistry (IHC)","time_frame":"Up to 2 years"},{"outcome_type":"primary","measure":"Incidence of adverse events (AEs)","time_frame":"Up to 2 years and 100 days"},{"outcome_type":"primary","measure":"Incidence of serious adverse events (SAEs)","time_frame":"Up to 2 years and 128 days"},{"outcome_type":"primary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to 2 years and 128 days"},{"outcome_type":"primary","measure":"Incidence of deaths","time_frame":"Up to 2 years and 128 days"},{"outcome_type":"primary","measure":"Progression-free survival (PFS) by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Progression-free survival rate (PFSR)","time_frame":"6 and 12 months","description":"PFS by BICR based on RECIST v1.1 criteria"},{"outcome_type":"secondary","measure":"PFS by investigator based on RECIST v1.1 criteria","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"PFSR","time_frame":"6 and 12 months","description":"PFS by investigator based on RECIST v1.1 criteria"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) based on RECIST v1.1 criteria","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Time to response (TTR) based on RECIST v1.1 criteria","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Duration of response (DOR) based on RECIST v1.1 criteria","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 3 years","description":"By arm"},{"outcome_type":"secondary","measure":"Overall survival rate (OSR)","time_frame":"Up to 3 years","description":"By arm"},{"outcome_type":"secondary","measure":"Measures of tumor fucosyl-GM1 (fuc-GM1) expression association with measures of anti-tumor activity measures (eg, ORR, PFS) (IHC)","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Measures of tumor fucosyl-GM1 (fuc-GM1) expression by targeted mass spectrometry","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Measures of tumor fucosyl-GM1 (fuc-GM1) expression association with measures of anti-tumor activity measures (eg, ORR, PFS) (targeted mass spectrometry)","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Measures of tumor programmed cell death-ligand 1 (PD-L1) expression combined positive score (CPS) at baseline","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Measures of tumor programmed cell death-ligand 1 (PD-L1) expression association with measures of anti-tumor activity (eg, ORR, PFS)","time_frame":"Up to 2 years"},{"outcome_type":"secondary","measure":"Immunogenicity of BMS-986012 measured by assessment of the presence of specific anti-drug antibodies (ADAs) to BMS-986012 (i.e. incidence of positive ADAs)","time_frame":"Up to 2 years"}]}
{"nct_id":"NCT04740307","start_date":"2021-03-16","phase":"Phase 2","enrollment":110,"brief_title":"Safety and Efficacy of Coformulated Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib (E7080/MK-7902) in Advanced Hepatocellular Carcinoma (MK-1308A-004)","official_title":"A Phase 2, Multicenter, Clinical Study to Evaluate the Safety and Efficacy of MK-1308A (Coformulated MK-1308/MK-3475) in Combination With Lenvatinib (E7080/MK-7902) in First-line Therapy of Participants With Advanced Hepatocellular Carcinoma","primary_completion_date":"2026-03-08","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-03-08","last_update":"2021-09-16","description":"The purpose of this study is to evaluate the safety and efficacy of fixed dose coformulated pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib in a first line (1L) hepatocellular carcinoma (HCC) setting. No hypothesis testing will be performed.","other_id":"1308A-004","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and\r\n             mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)\r\n\r\n          -  Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not\r\n             amenable to locoregional therapy or refractory to locoregional therapy, and not\r\n             amenable to a curative treatment approach\r\n\r\n          -  Has a Child-Pugh class A liver score within 7 days prior to first dose of study\r\n             intervention\r\n\r\n          -  Has a predicted life expectancy of >3 months\r\n\r\n          -  Has at least 1 measurable HCC lesion based on RECIST 1.1, confirmed by BICR\r\n\r\n          -  Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within\r\n             7 days prior to first dose of study intervention\r\n\r\n          -  Participants with controlled hepatitis B will be eligible as long as they meet the\r\n             following criteria: antiviral therapy for Hepatitis B virus (HBV) must be given for at\r\n             least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of\r\n             study drug\r\n\r\n          -  Has adequately controlled blood pressure with or without antihypertensive medications\r\n\r\n          -  Has adequate organ function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has had esophageal or gastric variceal bleeding within the last 6 months.\r\n\r\n          -  Has bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants\r\n             requiring therapeutic international normalized ratio (INR) monitoring, e.g., warfarin\r\n             or similar agents\r\n\r\n          -  Has clinically apparent ascites on physical examination\r\n\r\n          -  Has inferior vena cava or cardiac involvement of HCC based on imaging\r\n\r\n          -  Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive\r\n             to therapy\r\n\r\n          -  Has medical contraindications that preclude all forms of contrast-enhanced imaging\r\n             (computed tomography [CT] or magnetic resonance imaging [MRI])\r\n\r\n          -  Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other\r\n             condition that might affect the absorption of lenvatinib\r\n\r\n          -  Has a preexisting Grade 3 gastrointestinal or non-gastrointestinal fistula\r\n\r\n          -  Has clinically active hemoptysis (bright red blood of a least 0.5 teaspoon) within 3\r\n             weeks prior to the first dose of study drug\r\n\r\n          -  Has clinically significant cardiovascular impairment within 12 months of the first\r\n             dose of study intervention, including New York Heart Association (NYHA) Class III or\r\n             IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular\r\n             accident, or cardiac arrhythmia associated with hemodynamic instability\r\n\r\n          -  Has had major surgery to the liver within 4 weeks prior to the first dose of study\r\n             intervention\r\n\r\n          -  Has had a minor surgery (i.e., simple excision) within 7 days prior to the first dose\r\n             of study intervention (Cycle 1 Day 1)\r\n\r\n          -  Has serious nonhealing wound, ulcer, or bone fracture\r\n\r\n          -  Has received any systemic chemotherapy, including anti- vascular endothelial growth\r\n             factor (VEGF) therapy, or any systemic investigational anticancer agents for treatment\r\n             of HCC\r\n\r\n          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with\r\n             an agent directed to another stimulatory or coinhibitory T-cell receptor\r\n\r\n          -  Has received locoregional therapy to liver within 4 weeks prior to the first dose of\r\n             study intervention\r\n\r\n          -  Has received prior radiotherapy to a non-liver region within 2 weeks of start of study\r\n             intervention\r\n\r\n          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of\r\n             study drug\r\n\r\n          -  Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks prior to the first dose of\r\n             study intervention\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             or any other form of immunosuppressive therapy within 7 days prior the first dose of\r\n             study intervention\r\n\r\n          -  Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years\r\n\r\n          -  Has a known history of, or any evidence of, central nervous system (CNS) metastases\r\n             and/or carcinomatous meningitis as assessed by local site investigator\r\n\r\n          -  Has severe hypersensitivity (Grade 3) to study intervention and/or any of their\r\n             excipients\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n          -  Has a history of (noninfectious) pneumonitis/interstitial lung disease that required\r\n             steroids or has current pneumonitis/interstitial lung disease\r\n\r\n          -  Has an active infection requiring systemic therapy, with the exception of HBV or\r\n             Hepatitis C virus (HCV)\r\n\r\n          -  Has a known history of human immunodeficiency virus (HIV) infection\r\n\r\n          -  Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection\r\n             (anti-HCV antibody [Ab] positive and detectable HCV RNA) at study entry\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the study, interfere with the participant's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             the participant to participate, in the opinion of the treating investigator\r\n\r\n          -  Has a known psychiatric or substance abuse disorder that would interfere with the\r\n             participants ability to cooperate with the requirements of the study\r\n\r\n          -  Has had an allogenic tissue/solid organ transplant\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Advanced Hepatocellular Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab/Quavonlimab","description":"Pembrolizumab/Quavonlimab (400 mg/25 mg) administered via IV infusion Q6W."},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib 12 mg (body weight [BW] 60 kg) or 8 mg (BW <60 kg) administered orally every day (QD)."},{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Pembrolizumab (400 mg) administered via IV infusion Q6W, in the event of intolerable toxicity to pembrolizumab/quavonlimab."}],"outcomes":[{"outcome_type":"secondary","measure":"Time-To-Progression (TTP) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 28 months","description":"TTP is defined as the time from the first dose of study intervention to the first documented PD per RECIST 1.1 assessed by BICR. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 28 months","description":"OS is defined as the time from the first dose of study intervention to death due to any cause."},{"outcome_type":"primary","measure":"Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase","time_frame":"Cycle 1 (Up to approximately 3 weeks)","description":"DLTs will be defined as follows unless determined to be unrelated to study intervention: any Grade 4 nonhematologic toxicity (not laboratory); any Grade 4 hematologic toxicity lasting >7 days (Grade 4 lymphopenia lasting ≥21 days); Grade 3 platelet count decreased if associated with clinically significant hemorrhage; any Grade 3 nonhematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; any clinically significant Grade 3 or Grade 4 nonhematologic laboratory abnormality if: medical intervention is required to treat participant, or abnormality leads to hospitalization, or abnormality persists for >1 week (or bilirubin if persists >4 weeks); aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) >10.0 times upper limit of normal (ULN) or >10.0 times baseline if baseline >ULN; any febrile neutropenia Grade 3 or Grade 4; any treatment-related AE that causes the participant to discontinue study intervention during the DLT window; any Grade 5 toxicity"},{"outcome_type":"primary","measure":"Number of participants with ≥1 adverse event (AE)","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants with an AE will be reported."},{"outcome_type":"primary","measure":"Number of participants with ≥1 serious adverse event (SAE)","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. The number of participants with an SAE will be reported."},{"outcome_type":"primary","measure":"Number of participants with ≥1 immune-related AE (irAE)","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs associated with MK-1308A exposure may represent an immune-related response. irAEs pre-specified for this study include pneumonitis, diarrhea/colitis, Type 1 diabetes mellitus (T1DM) or hyperglycemia, hypophysitis, hyperthyroidism, hypothyroidism, nephritis (grading according to increased creatinine or acute kidney injury), and myocarditis. The number of participants with an irAE will be reported."},{"outcome_type":"primary","measure":"Number of participants with ≥1 hepatic AE","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Hepatic events of clinical interest (ECIs) include any of the following events if the event is considered not due to disease progression as judged by the investigator: among participants with Baseline ALT <2 × ULN: ALT ≥5 × ULN; among participants with Baseline ALT ≥2 × ULN: ALT >3 × the Baseline level; ALT >500 U/L regardless of baseline level; total bilirubin >3.0 mg/dL; hepatic decompensation diagnosed clinically (regardless of laboratory values) including new onset clinically detectable ascites requiring intervention for >3 days, hepatic encephalopathy, or gastrointestinal bleeding suggestive of portal hypertension. The number of participants with a hepatic AE will be reported."},{"outcome_type":"primary","measure":"Number of participants discontinuing study treatment due to an AE","time_frame":"Up to approximately 5 years","description":"An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants that discontinue study treatment due to an AE will be reported."},{"outcome_type":"primary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 28 months","description":"ORR is defined as the percentage of participants who achieve a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ, and assessed by BICR."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 28 months","description":"For participants who demonstrate confirmed CR or PR per RECIST 1.1 assessed by BICR, DOR is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions) until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 28 months","description":"DCR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions), PR (at least a 30% decrease in the SOD of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) after ≥6 weeks (the start of the window for the first scheduled scan) per RECIST 1.1 assessed by BICR. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR","time_frame":"Up to approximately 28 months","description":"PFS is defined as the time from the first dose of study intervention to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD."},{"outcome_type":"secondary","measure":"ORR per modified RECIST (mRECIST) as assessed by BICR","time_frame":"Up to approximately 28 months","description":"ORR is defined as the percentage of participants who achieve a confirmed CR (disappearance of any intratumoral arterial enhancement in all target lesions) or a PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions) per mRECIST as assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions."},{"outcome_type":"secondary","measure":"DOR per mRECIST as assessed by BICR","time_frame":"Up to approximately 28 months","description":"For participants who demonstrate confirmed CR or PR per mRECIST assessed by BICR, DOR is defined as the time from the first documented evidence of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions) until PD or death due to any cause, whichever occurs first. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started."},{"outcome_type":"secondary","measure":"DCR per mRECIST as assessed by BICR","time_frame":"Up to approximately 28 months","description":"DCR is defined as the percentage of participants who have achieved CR (disappearance of any intratumoral arterial enhancement in all target lesions), PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions), or SD (any cases that do not qualify for either PR or PD) after ≥6 weeks (the start of the window for the first scheduled scan) per mRECIST assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started."},{"outcome_type":"secondary","measure":"PFS per mRECIST as assessed by BICR","time_frame":"Up to approximately 28 months","description":"PFS is defined as the time from the first dose of study intervention to the first documented PD per mRECIST by BICR or death due to any cause, whichever occurs first. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started."},{"outcome_type":"secondary","measure":"TTP per mRECIST as assessed by BICR","time_frame":"Up to approximately 28 months","description":"TTP is defined as the time from the first dose of study intervention to the first documented PD per mRECIST assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started."}]}
{"nct_id":"NCT03850795","start_date":"2021-03-15","phase":"Phase 3","enrollment":430,"brief_title":"HC-1119 Versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)","official_title":"PROCADE: A Multinational Phase 3, Randomized, Double-Blind, Non-inferiority, Efficacy and Safety Study of Oral HC-1119 Versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)","primary_completion_date":"2022-11-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-05-31","last_update":"2021-09-13","description":"This study is a multinational Phase 3, randomized, double-blind, non-inferiority, efficacy and safety study of oral HC-1119 (80 mg/day) versus enzalutamide (160 mg/day) in asymptomatic or mildly symptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC). The following assessment of prostate cancer status will be collected during the course of the trial: soft tissue disease on computed tomography (CT) scan or on magnetic resonance imaging (MRI), bone disease on radionuclide bone scans, FACT-P and EQ-5D, Brief Fatigue Inventory, and PSA. Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs and physical examinations, safety laboratory evaluations, and 12-lead electrocardiograms (ECGs). Blood samples for population pharmacokinetics for HC-1119 and enzalutamide and related metabolites will be collected.","other_id":"HC1119-CS-03","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n        Subjects must meet the following inclusion criteria:\r\n\r\n          1. Age 18 or older and willing and able to give informed consent.\r\n\r\n          2. Histologically or cytologically confirmed adenocarcinoma of the prostate without\r\n             significant and relevant neuroendocrine differentiation or small cell features, per\r\n             investigator's judgment.\r\n\r\n          3. Ongoing ADT with a GnRH analogue, antagonist or bilateral orchiectomy (i.e., surgical\r\n             or medical castration).\r\n\r\n          4. For patients who have not had a bilateral orchiectomy, there must be a plan to\r\n             maintain effective GnRH analogue or antagonist therapy for the duration of the trial.\r\n\r\n          5. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit.\r\n\r\n          6. Patients receiving bisphosphonate or denosumab therapy must have been on stable doses\r\n             for at least four weeks (from Day 1 visit).\r\n\r\n          7. Progressive disease at study entry defined as one or more of the following three\r\n             criteria that occurred while the patient was on ADT as defined in eligibility\r\n             criterion #3:\r\n\r\n               1. PSA progression defined by a minimum of two rising PSA levels with an interval of\r\n                   1 week between each determination. Patients who received an anti-androgen agent\r\n                  must have progression after withdrawal ( 4 weeks since last flutamide or  6\r\n                  weeks since last bicalutamide or nilutamide). The PSA value at the Screening\r\n                  visit should be  2 g/L (2 ng/mL)\r\n\r\n               2. Soft tissue disease progression defined by RECIST 1.1\r\n\r\n               3. Bone disease progression defined by PCWG3 with two or more new lesions on bone\r\n                  scan\r\n\r\n          8. Metastatic disease documented by measurable soft tissue disease by CT/MRI per RECIST\r\n             1.1 criteria. Patients are allowed to have any metastatic disease (i.e. bone\r\n             metastasis) as long as they also have measurable soft tissue lesions per RECIST 1.1..\r\n\r\n          9. No prior cytotoxic chemotherapy for prostate cancer.\r\n\r\n         10. Asymptomatic or mildly symptomatic from prostate cancer.\r\n\r\n         11. ECOG performance status of 0-1 per the Investigators' clinical assessment\r\n\r\n         12. Estimated life expectancy of  6 months\r\n\r\n         13. Able to swallow the study drug and comply with study requirements\r\n\r\n         14. All sexually active patients are required to use a condom as well as meet 1 of the\r\n             following:\r\n\r\n               1. Patient is non-fertile (orchiectomy) or has a female partner of non-childbearing\r\n                  potential (i.e., post-menopausal, surgically sterilized, hysterectomy)\r\n\r\n               2. Patient and his female partner must agree to use an adequate contraceptive method\r\n                  from the first day of dosing until 3 months after the last dose to prevent\r\n                  pregnancies. Adequate contraceptive method is defined as:\r\n\r\n             i. Established use of oral, injected, or implanted hormonal methods of contraception.\r\n\r\n             ii. Placement of an intra-uterine device or intra-uterine system. iii. Occlusive cap\r\n             (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.\r\n\r\n             iv. Tubal ligation for at least 6 months prior to screening.\r\n\r\n         15. Male patient engaged in sexual activity with a pregnant female is required to use a\r\n             condom from the first day of dosing until 3 months after the last dose of treatment\r\n             with study drugs.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Subjects must NOT meet any of the following exclusion criteria:\r\n\r\n          1. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the\r\n             investigator, would make the patient inappropriate for enrollment.\r\n\r\n          2. Known or suspected brain metastasis or active leptomeningeal disease.\r\n\r\n          3. Regular daily use of opiate analgesics for pain from prostate cancer within four weeks\r\n             of enrollment (Day 1 visit).\r\n\r\n          4. WBC count < 3,000/L, or absolute neutrophil count < 1,500/L, or platelet count <\r\n             100,000/L, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients\r\n             may not have received any growth factors or blood transfusions or any therapeutic\r\n             invention within 14 days of the hematologic laboratory values obtained at the\r\n             Screening visit).\r\n\r\n          5. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >\r\n             2.5 times the upper limit of normal at the Screening visit; no therapeutic invention\r\n             within 14 days before screening.\r\n\r\n          6. Creatinine clearance < 30 mL/min as calculated using the Cockcroft-Gault equation at\r\n             the Screening visit. Creatinine Clearance (mL/min) = [[140-Age (years)] * Weight (kg)]\r\n             / [72 * Serum Creatinine (mg/dL)]\r\n\r\n          7. Albumin < 30 g/L (3.0 g/dL) at the Screening visit, no therapeutic invention within 14\r\n             days before screening.\r\n\r\n          8. History of another malignancy within the previous two years other than curatively\r\n             treated non-melanomatous skin cancer.\r\n\r\n          9. Treatment with flutamide within four weeks of enrollment (Day 1 visit).\r\n\r\n         10. Treatment with bicalutamide or nilutamide within six weeks of enrollment (Day 1\r\n             visit).\r\n\r\n         11. Treatment with 5- reductase inhibitors (finasteride, dutasteride), estrogens within\r\n             four weeks of enrollment (Day 1 visit).\r\n\r\n         12. Treatment with systemic biologic therapy for prostate cancer (other than approved bone\r\n             targeted agents) within four weeks of enrollment (Day 1 visit).\r\n\r\n         13. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are\r\n             known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater\r\n             than the equivalent of 10 mg of prednisone/prednisolone per day within four weeks of\r\n             enrollment (Day 1 visit).\r\n\r\n         14. Prior use, or participation in a clinical trial, of an agent that blocks androgen\r\n             synthesis (e.g., abiraterone) or blocks the AR (e.g., apalutamide, darolutamide,\r\n             enzalutamide, proxalutamide).\r\n\r\n         15. Participation in a previous clinical trial of HC-1119.\r\n\r\n         16. Use of an investigational agent within four weeks of enrollment (Day 1 visit).\r\n\r\n         17. Radiation therapy for treatment of the primary tumor within three weeks of enrollment\r\n             (Day 1 visit).\r\n\r\n         18. Radionuclide therapy (Radium 223) for treatment of metastasis within four weeks of\r\n             enrollment (Day 1 visit).\r\n\r\n         19. Clinically significant cardiovascular disease or condition\r\n\r\n         20. Treatment with strong CYP2C8 inhibitors and inducers, CYP3A4 inducers, medications\r\n             which are known to prolong the QT interval (see Appendix C).\r\n\r\n         21. History of seizure or any condition that may predispose to seizure.\r\n\r\n         22. Conditions that predispose subjects to increased risk for falls or fractures according\r\n             to the discretion of the Investigator.\r\n\r\n         23. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer\r\n             disease within last three months).\r\n\r\n         24. Major surgery within four weeks prior to enrollment (Day 1 visit).\r\n\r\n         25. Have active infection with HBV measured by hepatitis B surface antigen (HBsAg) test,\r\n             HCV measured by RNA test and HIV measured by antibody test.\r\n\r\n         26. Have known active tuberculosis.\r\n\r\n         27. Known hypersensitivity to HC-1119, enzalutamide, or any of the excipients.\r\n\r\n         28. Rare hereditary problems of fructose intolerance due to sorbitol\r\n      ","sponsor":"Hinova Pharmaceuticals USA, Inc.","sponsor_type":"Industry","conditions":"Prostate Cancer Metastatic|Castration-resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: HC-1119","description":"oral once daily 80 mg"},{"intervention_type":"Drug","name":"Drug: Enzalutamide","description":"oral once daily 160 mg"}],"outcomes":[{"outcome_type":"primary","measure":"Overall Response Rate (ORR)","time_frame":"Week 24","description":"To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall response rate (ORR) by RECIST 1.1."},{"outcome_type":"secondary","measure":"PSA decline of ≥50% from baseline","time_frame":"Week 24","description":"To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by decline of ≥50% from baseline"},{"outcome_type":"secondary","measure":"Radiographic Progression-free Survival (rPFS)","time_frame":"Week 24","description":"To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by radiographic progression-free survival (rPFS)"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Week 24","description":"To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall survival (OS)"},{"outcome_type":"secondary","measure":"Safety and Tolerability (based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0)","time_frame":"Week 24","description":"To determine the safety and tolerability of orally administrated HC-1119 as compared to enzalutamide based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0."}]}
{"nct_id":"NCT04712643","start_date":"2021-03-12","phase":"Phase 3","enrollment":342,"brief_title":"A Study of TACE Combined With Atezolizumab Plus Bevacizumab or TACE Alone in Patients With Untreated Heaptocellular Carcionma","official_title":"A Phase III, Open-Label, Randomized Study of On-Demand TACE Combined With Atezolizumab Plus Bevacizumab (Atezo/Bev) or On-Demand TACE Alone in Patients With Untreated Heaptocellular Carcionma","primary_completion_date":"2025-02-28","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-02-26","last_update":"2021-08-27","description":"This study will evaluate the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand TACE compared to on-demand TACE alone in participants with hepatocellular carcinoma who are unsuitable for curative therapy.","other_id":"ML42612","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Confirmed diagnosis of HCC by histology/ cytology or clinical criteria\r\n\r\n          -  Eligible for TACE treatment\r\n\r\n          -  No prior systemic therapy for HCC, especially immunotherapy\r\n\r\n          -  No prior locoregional therapy to the target lesion(s)\r\n\r\n          -  At least one measurable untreated lesion\r\n\r\n          -  ECOG Performance Status of 0-1\r\n\r\n          -  Child-Pugh class A\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Evidence of macrovascular invasion (MVI)\r\n\r\n          -  Evidence of extrahepatic spread (EHS)\r\n\r\n          -  Being a candidate for curative treatments\r\n\r\n          -  Any condition representing a contraindication to TACE as determined by the\r\n             investigators\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  Untreated or incompletely treated esophageal and/or gastric varices with bleeding or\r\n             high risk for bleeding\r\n\r\n          -  A prior bleeding event due to esophageal and/or gastric varices within 6 months prior\r\n             to initiation of study treatment\r\n\r\n          -  Evidence of bleeding diathesis or significant coagulopathy\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Hepatocellular Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until participant experience loss of clinical benefit as evaluated by the investigator or unacceptable toxicity or withdrawal of informed consent."},{"intervention_type":"Drug","name":"Drug: Becavizumab","description":"Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle."},{"intervention_type":"Device","name":"Device: Transarterial chemoembolization (TACE)","description":"TACE will be performed by clinical demand."}],"outcomes":[{"outcome_type":"primary","measure":"TACE Progression-Free Survival (TACE PFS) as Determined by IRC","time_frame":"Randomization to untreatable progression or TACE failure/refractoriness or death (up to approximately 48 months)","description":"TACE PFS is defined as the time from randomization to untreatable progression or TACE failure/refractoriness and any cause of death, as determined by the independent review committee (IRC)."},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Randomization to death from any cause (up to approximately 72 months)","description":"Overall survival (OS) after enrollment is defined as the time from randomization to death from any cause."},{"outcome_type":"secondary","measure":"TACE PFS as Determined by Investigator","time_frame":"Randomization to untreatable progression or TACE failure/refractoriness or death (up to approximately 48 months)","description":"TACE PFS as determined by the investigator."},{"outcome_type":"secondary","measure":"Time to Untreatable (unTACEable) Progression (TTUP)","time_frame":"Randomization to Child-Pugh B8 or worse, intrahepatic tumor progression, with new lesions NOT defined as tumor progression, MVI or EHS (up to approximately 48 months)","description":"Time to untreatable (unTACEable) progression (TTUP) is defined as time from randomization to Child-Pugh B8 or worse, intrahepatic tumor progression, with new lesions NOT defined as tumor progression, MVI or EHS, as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Time to Progression (TTP)","time_frame":"Randomization to unTACEable progression or TACE failure/refractoriness (up to approximately 48 months)","description":"Time to progression (TTP) is defined as the time from randomization to unTACEable progression or TACE failure/refractoriness, as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Time to Macrovascular Invasion (MVI)","time_frame":"Ranodimzation to first evidence of MVI (up to approximately 48 months )","description":"Time to MVI is defined as the time from randomization to the first evidence of MVI, as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Time to Extrahepatic Spread (EHS)","time_frame":"Randomization to first evidence of EHS (up to approximately 48 months)","description":"Time to EHS is defined as the time from randomization to the first evidence of EHS, as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Time to MVI/EHS","time_frame":"Randomization to first evidence of MVI/EHS (up to approximately 48 months)","description":"Time to MVI/EHS is defined as the time from randomization to the first evidence of MVI/EHS (whichever occurs first), as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Randomization up to approximately 72 months","description":"Objective response rate (ORR) is defined as the percentage of participants who have a complete or partial response, as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Duration of Responses (DOR)","time_frame":"First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 72 months)","description":"Duration of responses (DOR) is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the IRC and investigator."},{"outcome_type":"secondary","measure":"Time to Deterioration (TTD)","time_frame":"Randomization to first deterioration (up to approximately 72 months)","description":"TTD is defined as the time from randomization to first deterioration in the patient-reported GHS/QoL, physical function, or role function scales of the EORTC QLQ-C30."},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events","time_frame":"Baseline up to apporximately 72 months"}]}
{"nct_id":"NCT04675983","start_date":"2021-03-10","phase":"Phase 3","enrollment":540,"brief_title":"A Study of Sintilimab Plus Ramucirumab as First-line Treatment for G/EGJ Adenocarcinoma (ORIENT-106)","official_title":"A Randomized, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Sintilimab Combined With Ramucirumab as Compared to Chemotherapy for the First-line Treatment of Unresectable Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (ORIENT-106)","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-03-31","last_update":"2021-03-12","description":"The main purpose of this study is to evaluate the efficacy and safety of sintilimab plus ramucirumab compared to stand of care first-line chemotherapy in participants with advanced gastric or esophagogastric adenocarcinoma.","other_id":"CIBI308E302","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion criteria\r\n\r\n          -  Have a histologically confirmed diagnosis of gastric or gastroesophageal junction\r\n             adenocarcinoma\r\n\r\n          -  With HER2 negative and PD-L1 positive tumor tissue\r\n\r\n          -  Have fresh or archival tumor tissue samples within 6 months for PD-L1 expression test.\r\n\r\n          -  Age 18 and 75 years\r\n\r\n          -  Diagnosed as unresectable locally advanced or metastatic stage\r\n\r\n        Exclusion criteria\r\n\r\n          -  Have received any prior palliative systemic treatment for advanced gastric or\r\n             gastroesophageal junction adenocarcinoma.\r\n\r\n          -  Known to have central nervous system metastases, cancerous meningitis, or bone\r\n             metastases with a risk of paraplegia\r\n\r\n          -  Known bone metastasis with a risk of paraplegia.\r\n\r\n          -  Have any ascites that requires intervention.\r\n\r\n          -  With bilateral medium pleural effusion or unilateral large pleural effusion leading to\r\n             respiratory symptoms\r\n      ","sponsor":"Innovent Biologics (Suzhou) Co. Ltd.","sponsor_type":"Industry","conditions":"Gastric Adenocarcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Oxaliplatin","description":"Administered IV"},{"intervention_type":"Drug","name":"Drug: Capecitabine","description":"Administered orally"},{"intervention_type":"Drug","name":"Drug: Sintilimab","description":"Administered IV"},{"intervention_type":"Drug","name":"Drug: Ramucirumab","description":"Administered IV"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Administered IV"},{"intervention_type":"Drug","name":"Drug: 5-fluorouracil","description":"Administered IV"}],"outcomes":[{"outcome_type":"primary","measure":"Safety and tolerability of sintilimab plus ramucirumab,Overall survival (OS)","time_frame":"Randomization to Death from Any Cause, up to 60 months","description":"OS is time from the date of randomization to the date of death from any cause. If the participant is alive at the cutoff for analysis (or was lost to follow-up), OS data is censored for analysis on the last date the participant is known to be alive."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS)","time_frame":"Randomization to Radiological Disease Progression or Death from Any Cause (Up to 24 Months)","description":"PFS is time from the date of randomization to the date of radiographic documentation of progression (per RECIST v.1.1) or the date of death due to any cause, whichever is earlier. If a participant is not known to have died or have radiographic documented progression as of the data cutoff date for the analysis, the PFS time is censored at the last adequate tumor assessment date."},{"outcome_type":"secondary","measure":"Objective Response Rate [ORR] (Percentage of Participants With Complete Response [CR] or Partial Response [PR])","time_frame":"Randomization to Disease Progression (Up To 24 Months)","description":"Response is defined using RECIST v1.1. ORR is calculated as sum of the number of participants with CR and PR divided by the number of evaluable participants multiplied by 100."},{"outcome_type":"secondary","measure":"Disease Control Rate [DCR] (Percentage of Participants With Complete Response [CR], Partial Response [PR] or Stable Disease [SD])","time_frame":"Randomization to Disease Progression (Up To 24 Months)","description":"Response is defined using RECIST v1.1. DCR is calculated as sum of the number of participants with CR, PR, and SD divided by the number of evaluable participants multiplied by 100."},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)","description":"DoR is time from the date of first radiographic documentation of CR or PR to the date of first radiographic documentation of PD or death due to any cause. If a participant is not known to have died or have radiographically documented PD as of the data inclusion cutoff date, DOR is censored at the date of the last adequate tumor assessment."},{"outcome_type":"secondary","measure":"Number of participants experiencing an adverse event (AE)","time_frame":"Randomization to end of study (up to 24 months)","description":"An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. The number of participants who experienced an AE is reported for each arm according to the treatment received."}]}
{"nct_id":"NCT04686305","start_date":"2021-03-09","phase":"Phase 1","enrollment":136,"brief_title":"Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC","official_title":"A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)","primary_completion_date":"2023-12-13","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-13","last_update":"2021-09-16","description":"DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with durvalumab and chemotherapy in patients with HER2 positive advanced and metastatic non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.","other_id":"D967YC00001","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","intervention_model_description":"The study will consist of 2 parts:\r\nDose-escalation part and monotherapy arm (Part 1; second-line and third-line patients): The dose of T-DXd and chemotherapeutic components on Arms 1A, 1B and 1C (cisplatin, carboplatin or pemetrexed) will be modified during the dose-escalation part in order to find the RP2D. Durvalumab dose will remain fixed on the dose escalation part of the study. Arm 1D is the T-DXd monotherapy arm.\r\nDose-expansion part (Part 2; treatment nave patients for metastatic disease): may be initiated following dose escalation at the discretion of the sponsor.\r\nIn addition to safety and tolerability, the study will also assess preliminary efficacy based upon ORR, DoR, DCR, OS, PFS among treatment groups.","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":120,"population":"","criteria":"\n        Inclusion criteria:\r\n\r\n          -  Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC\r\n\r\n          -  Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic\r\n             setting.\r\n\r\n          -  Part 2: Treatment-nave for non curative treatment for locally advanced or metastatic\r\n             NSCLC.\r\n\r\n          -  Part 2: Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion\r\n             or other targetable alterations. Prior adjuvant, neoadjuvant therapies are permitted\r\n             if progression has occurred > 12 months from the end of last therapy\r\n\r\n          -  HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue\r\n\r\n          -  WHO / ECOG performance status of 0 or 1\r\n\r\n          -  Measurable target disease assessed by the investigator using RECIST 1.1\r\n\r\n          -  Has protocol defined adequate organ and bone marrow function\r\n\r\n        Exclusion criteria:\r\n\r\n          -  HER2 mutation if previously known\r\n\r\n          -  Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current\r\n             ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at\r\n             screening\r\n\r\n          -  Lung-specific intercurrent clinically significant illnesses including, but not limited\r\n             to, any underlying pulmonary disorder and prior pneumonectomy\r\n\r\n          -  Active primary immunodeficiency known HIV infection, or active hepatitis B or C\r\n             infection\r\n\r\n          -  Active infection including tuberculosis and uncontrolled infection requiring IV\r\n             antibiotics, antivirals, or antifungals\r\n\r\n          -  Spinal cord compression or clinically active central nervous system metastases,\r\n             defined as untreated and symptomatic, or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms\r\n\r\n          -  Medical history of myocardial infarction within 6 months before treatment assignment,\r\n             symptomatic CHF (New York Heart Association Class II to IV), clinically important\r\n             cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke\r\n\r\n          -  A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal\r\n             shunt, or CART (Concentrated Ascites Reinfusion Therapy)\r\n\r\n          -  Unresolved toxicities from previous anticancer therapy OR prior discontinuation of any\r\n             planned study therapy due to toxicity.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Locally Advanced or Metastatic Non-Small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Trastuzumab deruxtecan","description":"T-DXd: administered as an IV infusion"},{"intervention_type":"Biological","name":"Biological: Durvalumab","description":"Durvalumab: administered as an IV infusion"},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Cisplatin: administered as an IV infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Carboplatin: administered as an IV infusion"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Pemetrexed: administered as an IV infusion"}],"outcomes":[{"outcome_type":"primary","measure":"Frequency of AEs and SAEs","time_frame":"Safety will be assessed for approximately 20 months from informed consent","description":"Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0"},{"outcome_type":"secondary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"An average of approximately 12 months","description":"Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment"},{"outcome_type":"secondary","measure":"Duration of Response (DoR)","time_frame":"An average of approximately 20 months","description":"DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on RECIST assessment"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"An average of approximately 12 months","description":"DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on RECIST assessment"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"An average of approximately 20 months","description":"PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on RECIST assessment"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"An average of approximately 20 months","description":"OS is the time form the date of first dose of study treatment until death due to any cause"},{"outcome_type":"secondary","measure":"Frequency of AEs and SAEs","time_frame":"Safety will be assessed for approximately 20 months from informed consent","description":"Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) assessed by the serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181 in all arms","time_frame":"An average of approximately 20 months","description":"Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) assessed by the serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab","time_frame":"An average of approximately 20 months","description":"Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab, including T-DXd in combination with durvalumab"},{"outcome_type":"secondary","measure":"The immunogenicity of T-DXd and durvalumab assessed by the presence of ADAs for T-DXd and durvalumab","time_frame":"An average of approximately 20 months","description":"Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab."}]}
{"nct_id":"NCT04486378","start_date":"2021-03-08","phase":"Phase 2","enrollment":201,"brief_title":"A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer","official_title":"A Multi-site, Open-label, Phase II, Randomized, Controlled Trial to Compare the Efficacy of RO7198457 Versus Watchful Waiting in Resected, Stage II (High Risk) and Stage III Colorectal Cancer Patients Who Are ctDNA Positive Following Resection","primary_completion_date":"2023-09-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2027-07-31","last_update":"2021-09-08","description":"This is a multi-site, open-label, Phase II, randomized, trial to compare the efficacy of RO7198457 versus watchful waiting in patients with circulating tumor DNA (ctDNA) positive, surgically resected Stage II/III rectal cancer, or Stage II (high risk)/Stage III colon cancer.","other_id":"BNT122-01","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Patients must be a man or woman of at least 18 years of age.\r\n\r\n          -  Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III\r\n             colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by\r\n             pathology report). Stage II (high risk) colon cancer is defined as Stage II disease\r\n             with any of the following risk factors for recurrence:\r\n\r\n               -  T4\r\n\r\n               -  Grade  3.\r\n\r\n               -  Clinical presentation with bowel obstruction or perforation.\r\n\r\n               -  Histological signs of vascular, lymphatic or perineural invasion.\r\n\r\n               -  < 12 nodes examined.\r\n\r\n          -  Patients must have detectable ctDNA prior to start of adjuvant chemotherapy (AdCTx)\r\n             (except for the Biomarker Cohort).\r\n\r\n              ctDNA assay must be performed through this study or study BNT000-001 ctDNA screening\r\n             protocol.\r\n\r\n          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of\r\n             0-1.\r\n\r\n          -  Patients must have adequate hematologic and organ function.\r\n\r\n          -  Adequate tumor material in formalin-fixed paraffin embedded (FFPE) blocks or as\r\n             sectioned tissue (only upon approval by sponsor) must be available (as described in\r\n             the laboratory manual).\r\n\r\n          -  The patient has started a standard of care AdCTx within 8 weeks post-surgery and has\r\n             completed at least 3 months of treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Patients with uncontrolled intercurrent illness.\r\n\r\n          -  Diagnosed microsatellite instability (MSI) high tumors.\r\n\r\n          -  Prior therapy with any of the following:\r\n\r\n               -  Neo-adjuvant (radio)chemotherapy prior to surgery.\r\n\r\n               -  Treatment with systemic immunosuppressive medication within 2 weeks prior to\r\n                  initiation of trial treatment or anticipation of need for systemic\r\n                  immunosuppressive medication during trial treatment, with the exception of low\r\n                  dose steroids defined as 10 mg oral prednisone (or equivalent).\r\n\r\n               -  Current or recent (within the 28 days prior to randomization) treatment with\r\n                  another investigational drug.\r\n\r\n          -  Toxicities from previous anti-cancer therapies that have not resolved to baseline\r\n             levels or to Grade 1 or less except for alopecia and peripheral neuropathy.\r\n\r\n          -  Patients who developed metastatic disease.\r\n\r\n          -  Patients with known past or current malignancy other than inclusion diagnosis, except\r\n             for:\r\n\r\n               -  Cervical carcinoma of Stage 1B or less.\r\n\r\n               -  Non-invasive basal cell or squamous cell skin carcinoma.\r\n\r\n               -  Non-invasive, superficial bladder cancer.\r\n\r\n               -  Prostate cancer with a current PSA level < 0.1 ng/mL.\r\n\r\n               -  Any curable cancer with a complete response (CR) of > 2 years duration.\r\n\r\n          -  Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its\r\n             excipients.\r\n\r\n          -  Patients who had major surgery (e.g., surgery requiring general anesthesia) within 4\r\n             weeks before screening, or will not have fully recovered from surgery, or have surgery\r\n             planned during the time the patient are expected to participate in the trial.\r\n\r\n          -  Patients with active hepatitis B or C.\r\n\r\n          -  Patients who have a history of human immunodeficiency virus (HIV) antibody positivity,\r\n             or tests positive for HIV at screening.\r\n      ","sponsor":"BioNTech SE","sponsor_type":"Industry","conditions":"Colorectal Cancer Stage II|Colorectal Cancer Stage III","interventions":[{"intervention_type":"Drug","name":"Drug: RO7198457 intravenous (i.v.)","description":"RO7198457 administered as an IV infusion at protocol-specified intervals over 12 months."},{"intervention_type":"Other","name":"Other: Observational group (no intervention)","description":"watchful waiting"}],"outcomes":[{"outcome_type":"primary","measure":"Disease-free survival (DFS)","time_frame":"Through study completion, up to 5 years","description":"DFS defined as the time from randomization to occurrence of any of the following events, whichever occurs first:\r\nLocoregional recurrence or distant metastases as determined by an independent central radiology assessment.\r\nOccurrence of second primary (same or other) cancer as determined by an independent central radiology assessment.\r\nDeath from any cause.\r\nLoss to follow-up is censored."},{"outcome_type":"secondary","measure":"Relapse-free survival (RFS)","time_frame":"Through study completion, up to 5 years","description":"RFS is defined as the time from randomization to occurrence of any of the following events, whichever occurs first:\r\nLocoregional recurrence or distant metastases as determined by the investigator.\r\nDeath from any cause.\r\nOccurrence of second primary (same or other) cancer as determined by the investigator is ignored.\r\nLoss to follow-up is censored."},{"outcome_type":"secondary","measure":"Time to recurrence (TTR)","time_frame":"Through study completion, up to 5 years","description":"TTR is defined as the time from randomization to occurrence of any of the following events (i.e., events related to the same cancer), whichever occurs first:\r\nLocoregional recurrence or distant metastases as determined by the investigator.\r\nDeath from same cancer.\r\nOccurrence of second primary (same or other) cancer as determined by the investigator is ignored.\r\nLoss to follow-up and deaths from other cancer, non-cancer-related deaths, treatment-related deaths are censored."},{"outcome_type":"secondary","measure":"Time to treatment failure (TTF)","time_frame":"Through study completion, up to 5 years","description":"TTF is defined as the time from randomization to occurrence of any of the following events, whichever occurs first:\r\nLocoregional recurrence or distant metastases as determined by the investigator.\r\nOccurrence of second primary (same or other) cancer as determined by the investigator.\r\nDeath from any cause except non-cancer related death.\r\nLoss to follow-up and non-cancer-related deaths are censored."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Through study completion, up to 5 years","description":"OS defined as the time from randomization to death from any cause."},{"outcome_type":"secondary","measure":"Change of Circulating tumor DNA (ctDNA) status (every 3 months)","time_frame":"Through study completion, up to 5 years"},{"outcome_type":"secondary","measure":"Occurrence of treatment emergent adverse event (TEAE)","time_frame":"15 months","description":"TEAE, including Grade 3+, serious, fatal TEAE by relationship (AEs graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events, version 5.0 [CTCAE v5.0])"},{"outcome_type":"secondary","measure":"Occurrence of dose reduction and discontinuation of IMP due to a TEAE.","time_frame":"15 months"}]}
{"nct_id":"NCT04744831","start_date":"2021-03-05","phase":"Phase 2","enrollment":120,"brief_title":"Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer","official_title":"A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)","primary_completion_date":"2023-02-28","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-08-31","last_update":"2021-09-05","description":"This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).","other_id":"DS8201-A-U207","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        KEY Inclusion Criteria:\r\n\r\n        Participants must meet all of the following criteria to be eligible for\r\n        randomization/registration into the study:\r\n\r\n          1. Adults aged 20 years in Japan, Taiwan, and Korea, or those aged 18 years in other\r\n             countries, at the time the Informed Consent Forms (ICFs) are signed.\r\n\r\n          2. Pathologically-documented, unresectable, recurrent, or metastatic colorectal\r\n             adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue\r\n             B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status\r\n             identified in primary or metastatic site.\r\n\r\n          3. The following therapies should be included in prior lines of therapy:\r\n\r\n               1. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated\r\n\r\n               2. Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if\r\n                  clinically indicated\r\n\r\n               3. Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated\r\n\r\n               4. Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite\r\n                  instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational\r\n                  burden (TMB)-high, if clinically indicated\r\n\r\n          4. Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by\r\n             central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ\r\n             hybridization (ISH) +.\r\n\r\n          5. Presence of at least one measurable lesion assessed by the Investigator per Response\r\n             Evaluation Criteria In Solid Tumors (RECIST) version 1.1.\r\n\r\n          6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.\r\n\r\n          7. Has left ventricular ejection fraction (LVEF) 50% within 28 days before\r\n             randomization/registration.\r\n\r\n        KEY Exclusion Criteria:\r\n\r\n        Participants who meet any of the following criteria will be disqualified from entering the\r\n        study:\r\n\r\n          1. Medical history of myocardial infarction (MI) within 6 months before\r\n             randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart\r\n             Association Class II to IV). Participants with troponin levels above the upper limit\r\n             of normal (ULN) at Screening (as defined by the manufacturer), and without any\r\n             MI-related symptoms, should have a cardiologic consultation before\r\n             randomization/registration to rule out MI.\r\n\r\n          2. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to\r\n             >470 msec (female participants) or >450 msec (male participants) based on the average\r\n             of the Screening triplicate 12-lead electrocardiograms (ECGs).\r\n\r\n          3. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that\r\n             required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis\r\n             cannot be ruled out by imaging at Screening.\r\n\r\n          4. Lung-specific intercurrent clinically significant illnesses including, but not limited\r\n             to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the\r\n             randomization/registration, severe asthma, severe chronic obstructive pulmonary\r\n             disease [COPD], restrictive lung disease, pleural effusion, etc.).\r\n\r\n          5. Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid\r\n             arthritis, Sjgren syndrome, sarcoidosis, etc.) where there is documented, or a\r\n             suspicion of, pulmonary involvement at the time of Screening.\r\n\r\n          6. Prior pneumonectomy.\r\n\r\n          7. Has spinal cord compression or clinically active central nervous system metastases,\r\n             defined as untreated and symptomatic, or requiring therapy with corticosteroids or\r\n             anticonvulsants to control associated symptoms. Participants with clinically inactive\r\n             brain metastases may be included in the study. Participants with treated brain\r\n             metastases that are no longer symptomatic and who require no treatment with\r\n             corticosteroids or anticonvulsants may be included in the study if they have recovered\r\n             from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed\r\n             between the end of whole-brain radiotherapy and randomization/registration.\r\n\r\n          8. Participants with leptomeningeal carcinomatosis.\r\n\r\n          9. Has known human immunodeficiency virus (HIV) infection.\r\n\r\n         10. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence\r\n             of viral infection within 28 days before study randomization/registration.\r\n             Participants with past or resolved hepatitis B virus (HBV) infection are eligible if\r\n             hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core\r\n             antigen (anti-HBc) positive (+).\r\n\r\n             Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase\r\n             chain reaction is negative for HCV ribonucleic acid (RNA).\r\n\r\n         11. Previous treatment with a DXd-containing antibody-drug conjugate (ADC).\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Advanced Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: DS-8201a 5.4 mg/kg Q3W","description":"DS-8201a for injection will be administered intravenously (IV) at a dose of 5.4 mg/kg every 3 weeks (Q3W)"},{"intervention_type":"Drug","name":"Drug: DS-8201a 6.4 mg/kg Q3W","description":"DS-8201a for injection will be administered intravenously (IV) at a dose of 6.4 mg/kg every 3 weeks (Q3W)"}],"outcomes":[{"outcome_type":"primary","measure":"Change in Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2-overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA), 6 months after the last participant is registered for the primary analysis","description":"Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), will be assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Change in Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) and 6 months after the last participant is registered for the primary analysis","description":"Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), will be assessed by the Investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Change in Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) and 6 months after the last participant is registered for the primary analysis","description":"Duration of response (DoR) is defined as the time from the initial response (complete response [CR] or partial response [PR]) until documented tumor progression or death from any cause. DoR is only defined for participants who achieved confirmed CR or PR. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions."},{"outcome_type":"secondary","measure":"Change in Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) (DCR) and 6 months after the last participant is registered for the primary analysis (DCR, CBR)","description":"Disease control rate (DCR) is the sum of complete response (CR), partial response (PR), and stable disease (SD) rates. CR was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD); at least a 20% increase in the sum of diameters of target lesions. DCR based on Investigator assessments Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Change in Clinical Benefit Ratio Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) (DCR) and 6 months after the last participant is registered for the primary analysis (DCR, CBR)","description":"Clinical Benefit Ratio (CBR), defined as the proportion of participants who achieved complete response (CR), partial response (PR), and stable disease (SD) for at least 6 months. CR was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD); at least a 20% increase in the sum of diameters of target lesions. CBR based on the blinded independent central review (BICR) and CBR based on Investigator assessments Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Change in Progression Free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) (PFS) and 6 months after the last participant is registered for the primary analysis (PFS, OS)","description":"Progression-Free Survival (PFS), defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on the blinded independent central review (BICR) and Investigator assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Change in Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA) (PFS) and 6 months after the last participant is registered for the primary analysis (PFS, OS)","description":"Overall Survival (OS), defined as the time from date of randomization/registration until death from any cause."},{"outcome_type":"secondary","measure":"The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"12 weeks after the first 80 participants are randomized for Interim Analysis (IA), up to approximately 18 months.","description":"Treatment-emergent Adverse Events (TEAEs)"},{"outcome_type":"secondary","measure":"The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2 (HER2)-overexpressing Metastatic Colorectal Cancer","time_frame":"6 months after the last participant is registered for the primary analysis, up to approximately 30 months.","description":"Treatment-emergent Adverse Events (TEAEs)"},{"outcome_type":"secondary","measure":"Change from Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)","time_frame":"6 months after the last participant is registered or later","description":"The EORTC QLQ-C30 consists of 30 questions assessing global health-related quality of life, five aspects of subject functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher scores for functioning scales and global health status indicate a better level of functioning while higher scores on the symptom and single-item scales indicate a higher level of symptoms."},{"outcome_type":"secondary","measure":"Change from Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer 29 (QLQ-CR29)","time_frame":"6 months after the last participant is registered or later","description":"The EORTC QLQ-CR29 consists of functional scales (Body Image, Future projections, Weight, Sexual interest) and symptom scales (urinary frequency, blood and mucus in stool, stool frequency, urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, flatulence, fecal incontinence, sore skin, embarrassment, impotence, dyspareunia). All scales and single-item measurements range from 0 to 100. A higher score on a functional scale indicates better functioning. A higher score for a symptom scale/item indicates higher symptomatology and problem level."},{"outcome_type":"secondary","measure":"Patient-Reported Outcomes (PROs) in the EuroQol Questionnaire (EQ) of 5 Dimensions (5D) on a Standardized 5-level (5L) Descriptive Health Status Scale (EQ-5D-5L)","time_frame":"6 months after the last participant is registered or later","description":"The EQ-5D questionnaire is made up for two components; health state description and evaluation. The EQ-5D-5L is the health state description for measuring health status. The descriptive system comprises the 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants self-rate each dimension on a 5-point, categorical scale: no problems, slight problems, moderate problems, severe problems, and extreme problems."},{"outcome_type":"secondary","measure":"Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT)","time_frame":"6 months after the last participant is registered or later","description":"The PGI-TT item is included to assess how a patient perceives the overall tolerability of the study treatment over the past 7 days. This is a single-item questionnaire, and patients will rate the bother associated with any treatment-related symptoms using response options on a 5-point scale ranging from 1 (Not at all) to 5 (Very much); 1-Not at all, 2-A little bit, 3-Somewhat, 4-Quite a bit, 5-Very much. Higher scores indicate a worse outcome."},{"outcome_type":"secondary","measure":"Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS)","time_frame":"6 months after the last participant is registered or later","description":"The PGIS item is included to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. This is a single-item questionnaire, and patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 6-point scale ranging from 1 (No symptoms) to 6 (Very Severe); 1-No Symptoms, 2-Very Mild, 3-Mild, 4-Moderate, 5-Severe, 6-Very Severe. Higher scores indicate a worse outcome."},{"outcome_type":"secondary","measure":"Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores","time_frame":"6 months after the last participant is registered or later","description":"The PGIC item is included to assess how a patient perceives their overall change in health status since the start of study treatment. This is a single-item questionnaire, and patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse. Higher scores indicate a worse outcome."},{"outcome_type":"secondary","measure":"Inpatient Healthcare Resource Utilization","time_frame":"6 months after the last participant is registered or later","description":"Healthcare resource use will be captured/collected, including inpatient admissions, intensive care unit admissions, and length of stay in hospital."},{"outcome_type":"secondary","measure":"Serum Concentration of Trastuzumab Deruxtecan (T-DXd)","time_frame":"6 months after the last participant is registered or later"},{"outcome_type":"secondary","measure":"Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody","time_frame":"6 months after the last participant is registered or later"},{"outcome_type":"secondary","measure":"Serum Concentration of Active Metabolite MAAA-1181a","time_frame":"6 months after the last participant is registered or later"},{"outcome_type":"secondary","measure":"Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing antibodies (NAb) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd)","time_frame":"6 months after the last participant is registered or later"}]}
{"nct_id":"NCT04662255","start_date":"2021-03-05","phase":"Phase 3","enrollment":500,"brief_title":"Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)","official_title":"A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Nave Mantle Cell Lymphoma (BRUIN MCL-321)","primary_completion_date":"2024-08-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-02-28","last_update":"2021-09-21","description":"This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare LOXO-305 to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.","other_id":"LOXO-BTK-20019","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Confirmed MCL diagnosis\r\n\r\n          -  Previously treated with at least one prior line of systemic therapy for MCL\r\n\r\n          -  Measurable disease per Lugano criteria\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) 0-2\r\n\r\n          -  Absolute neutrophil count  0.75  109/L without granulocyte-colony stimulating factor\r\n             support within 7 days of screening\r\n\r\n          -  Hemoglobin  8 g/dL not requiring transfusion support or growth factors within 7 days\r\n             of screening\r\n\r\n          -  Platelets  50  109/L not requiring transfusion support or growth factors within 7\r\n             days of screening.\r\n\r\n          -  AST and ALT  3.0 x upper limit of normal (ULN).\r\n\r\n          -  Total bilirubin  1.5 x ULN.\r\n\r\n          -  Creatinine clearance of  30 mL/min according to Cockcroft/Gault Formula\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior treatment with an approved or investigational BTK inhibitor\r\n\r\n          -  History of bleeding diathesis\r\n\r\n          -  History of stroke or intracranial hemorrhage within 6 months of randomization\r\n\r\n          -  History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen\r\n             receptor modified T-cell (CAR-T) therapy within 60 days of randomization\r\n\r\n          -  Clinically significant cardiovascular disease\r\n\r\n          -  Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3\r\n             consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs\r\n\r\n          -  Known HIV infection or active HBV, HCV, or CMV infections\r\n\r\n          -  Clinically significant active malabsorption syndrome or other condition likely to\r\n             affect gastrointestinal (GI) absorption\r\n\r\n          -  Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers\r\n             and/or strong P-gp inhibitors.\r\n\r\n          -  Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K\r\n             antagonist.\r\n\r\n          -  Vaccination with live vaccine within 28 days prior to randomization\r\n      ","sponsor":"Loxo Oncology, Inc.","sponsor_type":"Industry","conditions":"Lymphoma, Mantle-Cell","interventions":[{"intervention_type":"Drug","name":"Drug: LOXO-305","description":"Oral LOXO-305"},{"intervention_type":"Drug","name":"Drug: Ibrutinib","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Acalabrutinib","description":"Oral"},{"intervention_type":"Drug","name":"Drug: Zanubrutinib","description":"Oral"}],"outcomes":[{"outcome_type":"primary","measure":"To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)","time_frame":"Up to approximately 24 months","description":"Assessed per Lugano criteria"},{"outcome_type":"secondary","measure":"To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms","time_frame":"Up to approximately 24 months","description":"Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death"},{"outcome_type":"secondary","measure":"To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms","time_frame":"Up to approximately 24 months","description":"Time from randomization to time when discontinuation criteria met"},{"outcome_type":"secondary","measure":"Time to worsening (TTW) of MCL-related symptoms","time_frame":"Up to approximately 24 months","description":"Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms."},{"outcome_type":"secondary","measure":"Comparative Tolerability as measured by proportion of time with high side effect burden","time_frame":"Up to approximately 24 months","description":"Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome."},{"outcome_type":"secondary","measure":"To compare Overall Response Rate (ORR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms","time_frame":"Up to approximately 24 months","description":"Assessed per Lugano criteria"},{"outcome_type":"secondary","measure":"To compare Duration of Response (DOR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms","time_frame":"Up to approximately 24 months","description":"Assessed per Lugano criteria"},{"outcome_type":"secondary","measure":"To compare Overall Survival of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms","time_frame":"Up to approximately 24 months","description":"Assessed by survival"}]}
{"nct_id":"NCT04693234","start_date":"2021-03-03","phase":"Phase 2","enrollment":167,"brief_title":"AdvanTIG-202: Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) in Participants With Previously Treated Recurrent or Metastatic Cervical Cancer","official_title":"Phase 2 Study Investigating Efficacy and Safety of Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Combined With or Without Anti-TIGIT Monoclonal Antibody BGB-A1217 in Patients With Previously Treated Recurrent or Metastatic Cervical Cancer","primary_completion_date":"2022-03-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-03-31","last_update":"2021-04-29","description":"This is an open-label, 2-cohort, multicenter, Phase 2 study to evaluate the efficacy and safety of tislelizumab combined with or without ociperlimab (BGB-A1217) in participants with previously treated recurrent or metastatic cervical cancer.","other_id":"BGB-A317-A1217-202","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Histologically or cytologically confirmed squamous cell carcinoma, adenosquamous\r\n             carcinoma, or adenocarcinoma of the cervix.\r\n\r\n          2. Progression on or after one or more lines of chemotherapy for management of recurrent\r\n             or metastatic disease and is not amenable to curative treatment (eg, systemic\r\n             chemotherapy, surgery, or radiotherapy).\r\n\r\n          3. Measurable disease as assessed by RECIST v1.1. Note: A lesion in an area subjected to\r\n             prior loco-regional therapy, including previous radiotherapy, is not considered\r\n             measurable unless there has been demonstrated progression in the lesion since the\r\n             therapy as defined by RECIST v1.1.\r\n\r\n          4. Participants must submit qualified archival tumor tissue (formalin-fixed\r\n             paraffin-embedded block containing tumor [preferred] or approximately 15 [at least 6]\r\n             unstained slides) with an associated pathology report, or agree to a tumor biopsy for\r\n             determination of Programmed death-ligand 1 (PD-L1) expression and other biomarker\r\n             analyses (fresh tumor biopsies are strongly recommended at baseline in participants\r\n             with readily accessible tumor lesions and who consent to the biopsies).\r\n\r\n          5. Participant must have adequate organ function as indicated by the screening laboratory\r\n             values obtained within 7 days before the first study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT or any other antibody\r\n             or drug specifically targeting T-cell costimulation or checkpoint pathways.\r\n\r\n          2. Any active malignancy  2 years before first dose of study drug except for the\r\n             specific cancer under investigation in this study and any locally recurring cancer\r\n             that has been treated curatively (eg, resected basal or squamous cell skin cancer,\r\n             superficial bladder cancer, carcinoma in situ of breast).\r\n\r\n          3. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent\r\n             drainage (recurrence within 2 weeks of intervention).\r\n\r\n          4. Any major surgical procedure  28 days before first dose of study drug. Participants\r\n             must have recovered adequately from the toxicity and/or complications from the\r\n             intervention before the first dose of study drug.\r\n\r\n          5. Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin,\r\n             etc.) or any investigational therapies within 14 days or 5 half-lives (whichever is\r\n             longer) before the first dose of study drug or has received palliative radiation\r\n             treatment or other local regional therapies within 14 days before the first dose of\r\n             study drug.\r\n      ","sponsor":"BeiGene","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Tislelizumab","description":"Administered as specified in the treatment arm"},{"intervention_type":"Drug","name":"Drug: Ociperlimab","description":"Administered as specified in the treatment arm"}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR) assessed by Independent Review Committee (IRC) per RECIST v1.1 for Cohort 1","time_frame":"approximately 3 years"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) assessed by investigator's review per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 for Cohort 1","time_frame":"approximately 3 years"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) assessed by both IRC and investigator's review per RECIST v1.1 for Cohort 2","time_frame":"approximately 3 years"},{"outcome_type":"secondary","measure":"Duration of Response (DOR) assessed by both IRC and investigator's review","time_frame":"approximately 3 years"},{"outcome_type":"secondary","measure":"Progression Free Survival (PFS) assessed by both IRC and investigator's review","time_frame":"Date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first, approximately 3 years"},{"outcome_type":"secondary","measure":"Time to Response (TTR) assessed by both IRC and investigator's review","time_frame":"date of first dose of study drug to first documentation of response, approximately 3 years"},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) assessed by both IRC and investigator's review","time_frame":"the proportion of patients who achieve CR, PR, or stable disease (SD) approximately 3 years"},{"outcome_type":"secondary","measure":"Clinical Benefit Rate (CBR) assessed by both IRC and investigator's review","time_frame":"the proportion of patients who achieve CR, PR, or durable SD (SD ≥ 24 weeks), approximately 3 years"},{"outcome_type":"secondary","measure":"Overall Survival (OS) assessed by both IRC and investigator's review","time_frame":"Date of first dose of study drug until the date of death from any cause for Cohorts 1 and 2, approximately 3 years"},{"outcome_type":"secondary","measure":"Health-related quality of life (HRQoL)","time_frame":"approximately 3 years","description":"Assessment of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)"},{"outcome_type":"secondary","measure":"Adverse events (AEs) and serious adverse events (SAEs) as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 for Cohorts 1 and 2","time_frame":"approximately 3 years"},{"outcome_type":"secondary","measure":"Serum BGB-A1217 and tislelizumab concentrations at specified timepoints","time_frame":"specified timepoints up to 30 (±7) days after last dose, approximately 3 years"},{"outcome_type":"secondary","measure":"Immunogenic responses to BGB-A1217 and tislelizumab, evaluated through the detection of antidrug antibodies (ADAs)","time_frame":"date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first, approximately 3 years"},{"outcome_type":"secondary","measure":"Health-related quality of life (HRQoL)","time_frame":"approximately 3 years","description":"Assessment of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module (EORTC QLQ-CX24)"}]}
{"nct_id":"NCT04665843","start_date":"2021-03-02","phase":"Phase 2","enrollment":120,"brief_title":"A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck","official_title":"A Phase II, Randomized, Double Blind Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Patients With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck","primary_completion_date":"2023-02-28","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-08-31","last_update":"2021-08-25","description":"The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.","other_id":"BO42533","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed recurrent/metastatic SCCHN involving the\r\n             oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local\r\n             therapies\r\n\r\n          -  Known results from human papillomavirus (HPV) status test for oropharyngeal carcinoma\r\n\r\n          -  No prior systemic therapy for metastatic and/or recurrent SCCHN\r\n\r\n          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\r\n\r\n          -  Tumor PD-L1 expression as determined by PD-L1 immunohistochemistry assay\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1\r\n\r\n          -  Life expectancy >=12 weeks\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Disease suitable for local therapy with curative intent\r\n\r\n          -  Progressive or recurrent disease within 6 months of the last dose of curative intent\r\n             systemic treatment for locally advanced SCCHN\r\n\r\n          -  Grade >=2 unresolved toxicity related to surgery or other prior therapies\r\n\r\n          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)\r\n             metastases\r\n\r\n          -  History of leptomeningeal disease\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced\r\n             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening\r\n             chest computed tomography (CT) scan\r\n\r\n          -  History of additional malignancy other than SCCHN within 5 years prior to\r\n             randomization\r\n\r\n          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including\r\n             anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1 therapeutic antibodies\r\n\r\n          -  Treatment with systemic immunostimulatory agents or systemic immunosuppressive\r\n             medication\r\n\r\n          -  Pregnancy or breastfeeding\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Squamous Cell Carcinoma of Head and Neck","interventions":[{"intervention_type":"Drug","name":"Drug: Tiragolumab","description":"Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle."}],"outcomes":[{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 43 months"},{"outcome_type":"secondary","measure":"Progression-Free Survival Rate at 6 Months","time_frame":"Month 6"},{"outcome_type":"secondary","measure":"Overall Survival Rate at 6 Months and 12 Months","time_frame":"Month 6, Month 12"},{"outcome_type":"secondary","measure":"Time to Confirmed Deterioration (TTCD) in Patient-Reported Physical Functioning","time_frame":"Up to approximately 43 months"},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events (AEs)","time_frame":"Up to approximately 43 months"},{"outcome_type":"primary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"Up to approximately 43 months"},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to approximately 43 months"},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS)","time_frame":"Up to approximately 43 months"},{"outcome_type":"secondary","measure":"Minimum Serum Concentration (Cmin) of Atezolizumab","time_frame":"Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months"},{"outcome_type":"secondary","measure":"Maximum Serum Concentration (Cmax) of Atezolizumab","time_frame":"Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months"},{"outcome_type":"secondary","measure":"Cmin of Tiragolumab","time_frame":"Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months"},{"outcome_type":"secondary","measure":"Cmax of Tiragolumab","time_frame":"Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months"},{"outcome_type":"secondary","measure":"Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab","time_frame":"From baseline up to approximately 43 months"},{"outcome_type":"secondary","measure":"Number of Participants With ADAs to Tiragolumab","time_frame":"From baseline up to approximately 43 months"}]}
{"nct_id":"NCT04586231","start_date":"2021-02-25","phase":"Phase 3","enrollment":708,"brief_title":"A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)","official_title":"An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib for Second-line or Third-line Treatment in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy","primary_completion_date":"2024-12-23","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-23","last_update":"2021-09-17","description":"This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.","other_id":"6482-011","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).\r\n\r\n          -  Disease progression on or after having received systemic treatment with\r\n             anti-programmed cell death-1/ligand 1 (PD-1/L1) for locally advanced or metastatic\r\n             RCC.\r\n\r\n          -  Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.\r\n\r\n          -  Karnofsky performance status (KPS) score of at least 70% assessed within 10 days\r\n             before randomization.\r\n\r\n          -  Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy\r\n             of a tumor lesion not previously irradiated.\r\n\r\n          -  Received no more than 2 prior systemic regimens for locally advanced or metastatic\r\n             RCC.\r\n\r\n          -  Received only 1 prior antiPD-1/L1 therapy for locally advanced or metastatic RCC.\r\n\r\n          -  A male participant is eligible to participate if he is abstinent from heterosexual\r\n             intercourse or agrees to use contraception during the intervention period and for at\r\n             least 7 days after the last dose of belzutifan or lenvatinib in the\r\n             belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of\r\n             cabozantinib.\r\n\r\n          -  A female participant is eligible to participate if she is not pregnant, not\r\n             breastfeeding, and at least 1 of the following conditions applies: Not a woman of\r\n             childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive\r\n             guidance during the intervention period and for at least 30 days after the last dose\r\n             of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last\r\n             dose of study intervention in the cabozantinib arm.\r\n\r\n          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within\r\n             24 hours before the first dose of study intervention.\r\n\r\n          -  Adequately controlled blood pressure.\r\n\r\n          -  Adequate organ function.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first\r\n             dose of study intervention.\r\n\r\n          -  Hypoxia (pulse oximeter reading <92% at rest), requires intermittent supplemental\r\n             oxygen, or requires chronic supplemental oxygen.\r\n\r\n          -  Known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years except for basal cell carcinoma of the skin, squamous cell\r\n             carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in\r\n             situ) that have undergone potentially curative therapy.\r\n\r\n          -  Known central nervous system (CNS) metastases and/or carcinomatous meningitis.\r\n\r\n          -  Clinically significant cardiac disease within 6 months of first dose of study\r\n             intervention.\r\n\r\n          -  Prolongation of QTc interval to >480 ms.\r\n\r\n          -  Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not\r\n             clinically stable.\r\n\r\n          -  Pre-existing Grade 3 gastrointestinal or nongastrointestinal fistula.\r\n\r\n          -  Moderate to severe hepatic impairment.\r\n\r\n          -  History of significant bleeding within 3 months before randomization.\r\n\r\n          -  History of solid organ transplantation.\r\n\r\n          -  Known psychiatric or substance abuse disorder that would interfere with cooperation\r\n             with the requirements of the study.\r\n\r\n          -  Unable to swallow orally administered medication or has a gastrointestinal disorder\r\n             affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).\r\n\r\n          -  Known hypersensitivity or allergy to the active pharmaceutical ingredients or any\r\n             component of the study intervention formulations.\r\n\r\n          -  Received colony-stimulating factors [eg, granulocyte colony-stimulating factor\r\n             (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant\r\n             erythropoietin (EPO)] within 28 days before randomization.\r\n\r\n          -  Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2\r\n             inhibitor.\r\n\r\n          -  Prior treatment with lenvatinib.\r\n\r\n          -  Prior treatment with cabozantinib.\r\n\r\n          -  Currently participating in a study of an investigational agent or using an\r\n             investigational device.\r\n\r\n          -  Active infection requiring systemic therapy.\r\n\r\n          -  History of human immunodeficiency virus (HIV) infection.\r\n\r\n          -  History of hepatitis B or known active hepatitis C infection.\r\n\r\n          -  History or current evidence of any condition, therapy, or laboratory abnormality that\r\n             might confound the results of the study, interfere with the participant's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             the participant to participate, in the opinion of the treating investigator.\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Carcinoma, Renal Cell","interventions":[{"intervention_type":"Drug","name":"Drug: Belzutifan","description":"Immediate-release 40 mg tablet"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Capsule available in 4 mg and 10 mg dosages"},{"intervention_type":"Drug","name":"Drug: Cabozantinib","description":"Tablet available in 20 mg, 40 mg and 60 mg dosages"}],"outcomes":[{"outcome_type":"primary","measure":"Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 34 months","description":"PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented."},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 44 months","description":"OS is defined as time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 24 months","description":"ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","time_frame":"Up to approximately 44 months","description":"For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review will be presented."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced One or More Adverse Events (AEs)","time_frame":"Up to approximately 44 months","description":"An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)","time_frame":"Up to approximately 44 months","description":"An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention."}]}
{"nct_id":"NCT04647526","start_date":"2021-02-25","phase":"Phase 3","enrollment":415,"brief_title":"Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment","official_title":"A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)","primary_completion_date":"2023-03-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2028-03-31","last_update":"2021-09-21","description":"The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).","other_id":"PBP-301","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Male aged 18 years or older.\r\n\r\n          2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the\r\n             prostate.\r\n\r\n          3. Ineligible or averse to chemotherapeutic treatment options.\r\n\r\n          4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the\r\n             following criteria:\r\n\r\n               1. Serum/plasma PSA progression defined as increase in PSA greater than 25% and >2\r\n                  ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks\r\n                  apart.\r\n\r\n               2. Soft-tissue progression defined as an increase 20% in the sum of the diameter\r\n                  (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all\r\n                  target lesions based on the smallest SOD since treatment started or the\r\n                  appearance of one or a new lesion.\r\n\r\n               3. Progression of bone disease: evaluable disease or one new bone lesion by bone\r\n                  scan\r\n\r\n          5. Previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or\r\n             apalutamide) in either the CSPC or CRPC setting.\r\n\r\n          6. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the\r\n             sponsor's central reader.\r\n\r\n          7. Castrate circulating testosterone levels (<1.7 nmol/L or <50 ng/dL).\r\n\r\n          8. Adequate organ function, independent of transfusion:\r\n\r\n             a. Bone marrow reserve: i. White blood cell (WBC) count 2.5  109/L OR absolute\r\n             neutrophil count (ANC) 1.5  109/L.\r\n\r\n             ii. Platelets 100  109/L. iii. Hemoglobin 8 mmol/L. b. Liver function: i. Total\r\n             bilirubin 1.5  institutional upper limit of normal (ULN). For patients with known\r\n             Gilbert's syndrome, 3  ULN is permitted.\r\n\r\n             ii. ALT or AST 3.0 ULN. c. Renal function: i. Serum/plasma creatinine 1.5  ULN or\r\n             creatinine clearance 50 mL/min based on Cockcroft-Gault formula.\r\n\r\n             d. Albumin 30 g/L.\r\n\r\n          9. Human immunodeficiency virus-infected patients who are healthy and have a low risk of\r\n             acquired immunodeficiency syndrome-related outcomes are included in this trial.\r\n\r\n         10. For patients who have partners of childbearing potential: Partner and/or patient must\r\n             use a method of birth control with adequate barrier protection, deemed acceptable by\r\n             the principal investigator during the study and for 6 months after last study drug\r\n             administration.\r\n\r\n         11. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified\r\n             by investigator, if randomized to Treatment Arm B.\r\n\r\n         12. ECOG performance status 0 to 1.\r\n\r\n         13. Willing and able to comply with all study requirements and treatments (including 177Lu\r\n             PNT2002) as well as the timing and nature of required assessments.\r\n\r\n         14. Signed informed consent.\r\n\r\n        Exclusion Criteria:\r\n\r\n        Patients are excluded from the study if any of the following criteria apply:\r\n\r\n          1. Prostate cancer with known significant (>10%) sarcomatoid or spindle cell or\r\n             neuroendocrine components. Any small cell component in the cancer should result in\r\n             exclusion.\r\n\r\n          2. Prior treatment for prostate cancer 28 days prior to randomization, with the\r\n             exclusion of first-line local external beam, ARAT, luteinizing hormone-releasing\r\n             hormone (LHRH) therapy, or non-radioactive bone-targeted agents.\r\n\r\n          3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel);\r\n             chemotherapy for hormone-sensitive prostate cancer (HSPC) is allowed if the last dose\r\n             was administered >1 year prior to consent.\r\n\r\n          4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium\r\n             89).\r\n\r\n          5. Prior immuno-therapy, except for sipuleucel-T.\r\n\r\n          6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.\r\n\r\n          7. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer.\r\n\r\n          8. Patients who have had 2 or more lines of ARATs.\r\n\r\n          9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) must be on\r\n             stable doses for at least 4 weeks prior to randomization.\r\n\r\n         10. Administration of an investigational agent 60 days or 5 half-lives, whichever is\r\n             shorter, prior to randomization.\r\n\r\n         11. Major surgery 30 days prior to randomization.\r\n\r\n         12. Estimated life expectancy <6 months as assessed by the principal investigator.\r\n\r\n         13. Presence of liver metastases >1 cm on abdominal imaging.\r\n\r\n         14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased\r\n             skeletal radioisotope uptake relative to soft tissues in association with absent or\r\n             faint genitourinary tract activity71.\r\n\r\n         15. Use of opioids for cancer-related pain 30 days prior to consent.\r\n\r\n         16. Known presence of central nervous system metastases.\r\n\r\n         17. Contraindications to the use of planned ARAT therapy.\r\n\r\n         18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non\r\n             melanoma skin cancer.\r\n\r\n         19. Concurrent illness that may jeopardize the patient's ability to undergo study\r\n             procedures.\r\n\r\n         20. Serious psychological, familial, sociological, or geographical condition that might\r\n             hamper compliance with the study protocol and follow-up schedule. Patients that travel\r\n             need to be capable of repeated visits even if they are on the control arm.\r\n\r\n         21. Symptomatic cord compression, or clinical or radiologic findings indicative of\r\n             impending cord compression.\r\n\r\n         22. Concurrent serious (as determined by the investigator) medical conditions, including,\r\n             but not limited to, New York Heart Association class III or IV congestive heart\r\n             failure (see 12.1 Appendix 1), unstable ischemia, uncontrolled symptomatic arrhythmia,\r\n             history of congenital prolonged QT syndrome, uncontrolled infection, known active\r\n             hepatitis B or C, or other significant co-morbid conditions that in the opinion of the\r\n             investigator would impair study participation or cooperation.\r\n      ","sponsor":"POINT Biopharma","sponsor_type":"Industry","conditions":"Metastatic Castration-Resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: [Lu-177]-PNT2002","description":"Participants randomized to Arm A will receive 6.8 GBq (10%) of [Lu-177]-PNT2002 every 8 weeks for 4 cycles"},{"intervention_type":"Drug","name":"Drug: Abiraterone","description":"Abiraterone (1000 mg orally qd with: 5 mg bid prednisone or 0.5 mg qd dexamethasone)"},{"intervention_type":"Drug","name":"Drug: Enzalutamide","description":"Enzalutamide (160 mg orally qd)"}],"outcomes":[{"outcome_type":"primary","measure":"Radiographic Progression Free Survival (rPFS)","time_frame":"32 weeks","description":"Time in months from the date of randomization to radiological progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) or confirmed progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3) (bone), or death from any cause, as assessed by blinded independent central review (BICR)."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"32 weeks","description":"Proportion of patients with partial or complete response (PR or CR, respectively) by BICR based on RECIST 1.1 criteria (soft tissue) and PCWG3 criteria (bone)."},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"32 weeks","description":"Time from the first date of CR or PR by BICR to the first occurrence of radiographic progression (PD) by BICR based on PCWG3 modified RECIST 1.1."},{"outcome_type":"secondary","measure":"Overall Survival","time_frame":"5 years","description":"Time from the date of randomization until death due to any cause."},{"outcome_type":"secondary","measure":"PSA Response","time_frame":"32 weeks","description":"Proportion of patients achieving a ≥50% decrease in PSA (PCWG3 criteria) from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later."},{"outcome_type":"secondary","measure":"Biochemical Progression-Free Survival (bPFS)","time_frame":"32 weeks","description":"Time from randomization to the date of the first PSA increase from baseline ≥25% and ≥2 ng/mL above nadir confirmed by a second PSA measurement defining progression ≥3 weeks later, as per PCWG3."},{"outcome_type":"other","measure":"Safety and Tolerability (AEs)","time_frame":"5 years","description":"Frequency and severity of AEs, graded and categorized using CTCAE v. 5.0."}]}
{"nct_id":"NCT04835142","start_date":"2021-02-24","phase":"Phase 3","enrollment":686,"brief_title":"Comparison of A140 and Erbitux Combined With mfolfox6 to Evaluate Efficacy and Safety of First-line Treatment for Ras Wild-type mCRC","official_title":"Phase III Clinical Study Comparison of A140 and Erbitux Combined With mfolfox6 to Evaluate Efficacy and Safety of First-line Treatment for Ras Wild-type mCRC","primary_completion_date":"2022-08-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-04-30","last_update":"2021-04-13","description":"Compare the objective remission rate of A140 and Erbitux combined with mfolfox6 regimen in the first-line treatment of Ras wild-type metastatic colorectal cancer for 12 weeks","other_id":"KL140--02-CTP","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Be able to understand the procedures and methods of this study, be willing to strictly\r\n             abide by the clinical trial protocol to complete this trial, and sign the informed\r\n             consent voluntarily\r\n\r\n          -  Male or female subjects aged 18-75 years (including 18 and 75 years)\r\n\r\n          -  Histologically proven diagnosis of metastatic colorectal cancer. No previous systemic\r\n             chemotherapy for metastatic colorectal cancer. Patients who have completed adjuvant\r\n             chemotherapy before the start of the study can be enrolled, Platinum containing\r\n             chemotherapy needs to end for more than 12 months, and non platinum containing\r\n             chemotherapy needs to end for more than 6 months;\r\n\r\n          -  KRAS and NRAS genotypes in tumor tissues were wild type, and BRAF-V600E mutation was\r\n             not found\r\n\r\n          -  At least one measurable lesion by computer tomography(CT) or magnetic resonance\r\n             imaging (MRI)according to RECIST1.1 criteria (not in an irradiated area)\r\n\r\n          -  Eastern Cooperative Oncology Group(ECOG)performance status of 0 or 1 at trial entry\r\n\r\n          -  Life expectancy of at least 16 weeks\r\n\r\n          -  The level of organ function before the first medication met the following\r\n             requirements:\r\n\r\n               1. Peripheral blood cell count: leukocyte count  3109 / L, neutrophil count \r\n                  1.5 109 / L, platelet count  75  109 / L, hemoglobin  90 g / L;\r\n\r\n               2. Liver function: total bilirubin  1.5 ULN, Aspartate transaminase (AST) and\r\n                  alanine transaminase (ALT)  2.5 ULN; AST and ALT 5 ULN in subjects with liver\r\n                  metastasis;\r\n\r\n               3. Renal function: serum creatinine  1.5 ULN.\r\n\r\n          -  Fertile subjects (male and female) were required to receive effective medical\r\n             contraceptive measures until 3 months after the last study (see Annex 4 for specific\r\n             contraceptive measures).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Those who are known to have an allergic reaction to any component of the study drug\r\n\r\n          -  Local treatments such as radiotherapy, radiofrequency ablation, intervention, etc or\r\n             surgical procedures (excluding prior diagnostic biopsy) in the 28 days before first\r\n             administration\r\n\r\n          -  Known brain metastasis and/or leptomeningeal disease\r\n\r\n          -  People with complete intestinal obstruction and incomplete intestinal obstruction\r\n             requiring treatment. However, patients whose obstruction is relieved by fistula or\r\n             stent placement can be included in the group;\r\n\r\n          -  Active severe clinical infection (> Grade 2, NCI-CTCAE version 5.0), including active\r\n             tuberculosis\r\n\r\n          -  Uncontrolled diabetes (fasting blood glucose 10 mmol/L), severe lung disease (such as\r\n             acute lung disease, pulmonary fibrosis that affects lung function, interstitial lung\r\n             disease. Except for radiation pneumonia that has recovered), liver failure\r\n\r\n          -  Clinically significant cardiovascular diseases, such as heart failure (NYHA-),\r\n             uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, hypertension\r\n             (systolic blood pressure>150mmHg and/or diastolic blood pressure>100mmHg),\r\n             echocardiography The figure shows the ejection fraction <50%, the history of\r\n             myocardial infarction within the past two years\r\n\r\n          -  Renal replacement therapy\r\n\r\n          -  > Grade 1 Peripheral Nerve Disorder (NCI-CTCAE Version 5.0)\r\n\r\n          -  History of organ allograft, autologous stem cell transplantation, or allogeneic stem\r\n             cell transplantation\r\n\r\n          -  Previous malignancy other than CRC in the last 5 years except basal cell cancer of the\r\n             skin or preinvasive cancer of the cervix\r\n\r\n          -  HIV infection, hepatitis B surface antigen positive (and peripheral blood hepatitis B\r\n             virus deoxynucleotide HBV DNA  1104 copy number/ml or  2000 IU/ml), hepatitis C\r\n             virus antibody positive (and peripheral blood hepatitis C virus nucleotide HCV RNA\r\n             1103 copies/ml or  200 IU/ml)\r\n\r\n          -  Patients with coagulation dysfunction, meet any of the following conditions:\r\n             prothrombin time (PT)  1.5 ULN thrombin time (TT)  1.5 ULN,activated partial\r\n             thromboplastin time (APTT)  1.5 ULN;\r\n\r\n          -  Previously treatment with VEGF pathway targeted therapy and EGFR monoclonal antibody\r\n\r\n          -  Past treatment history:\r\n\r\n               1. Receiving other anti-tumor treatments (including anti-tumor treatments with\r\n                  traditional Chinese medicines, such as Aidi injection, Kanglaite injection,\r\n                  Kangai injection, cininobufosin, brucea javanica oil, etc.) within 4 weeks before\r\n                  the first administration of the study \r\n\r\n               2. Long-term systemic immunotherapy, or hormone therapy for anti-tumor purposes\r\n                  (physiological replacement therapy, except for those with hypothyroidism who take\r\n                  thyroxine);\r\n\r\n               3. Have received G-CSF, GM-CSF, whole blood or blood component transfusions within 4\r\n                  weeks before the first medication of the study;\r\n\r\n               4. Have received other experimental drugs or interventional clinical studies within\r\n                  4 weeks before the first medication of the study\r\n\r\n          -  Pregnancy (confirmed by blood pregnancy test) or lactation\r\n\r\n          -  There is currently alcohol or drug dependence\r\n\r\n          -  There is a clear neurological disease or mental illness that has not been cured,\r\n             including epilepsy, dementia, schizophrenia, etc\r\n\r\n          -  Adverse events of previous treatment (except for hair loss) did not return to grade 1\r\n             or below (NCI-CTCAE version 5.0)\r\n\r\n          -  The researcher believes that the patient has other factors that affect the efficacy or\r\n             safety evaluation of this study\r\n      ","sponsor":"Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.","sponsor_type":"Industry","conditions":"Metastatic Colorectal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Double blind control period A140","description":"experiment arm Drug A140:400 mg/m2D1iv,250 mg/m2qwiv Drug Oxaliplatin 85 mg/m2D1,iv), Drug Calcium Folinate 400 mg/m2D1,iv Drug 5-FU 400 mg/m2D1,iv2400 mg/m2 (484h) control arm: Drug Erbitux:400 mg/m2D1iv,250 mg/m2qwiv Drug Oxaliplatin 85 mg/m2D1,iv) Drug Calcium Folinate 400 mg/m2D1,iv Drug 5-FU 400 mg/m2D1,iv2400 mg/m2 (484h)"},{"intervention_type":"Drug","name":"Drug: Open single period A140","description":"Drug A140:400 mg/m2D1iv,250 mg/m2qwiv Drug Oxaliplatin 85 mg/m2D1,iv), Drug Calcium Folinate 400 mg/m2D1,iv Drug 5-FU 400 mg/m2D1,iv2400 mg/m2 (484h)"}],"outcomes":[{"outcome_type":"primary","measure":"ORR","time_frame":"16 Weeks","description":"The objective tumor response rate (ORR) of colorectal cancer patients at 12 weeks based on the evaluation of the independent imaging evaluation committee, and confirmed at least 4 weeks later"},{"outcome_type":"secondary","measure":"ORR","time_frame":"16 Weeks","description":"1)Based on the researcher's assessment of the objective tumor response rate (ORR) of patients with colorectal cancer after 12 weeks of medication, and confirmed at least 4 weeks later"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"PFS-1 year","description":"2)PFS within 1 year after medication based on the evaluation by the independent imaging evaluation committee and the investigator"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"OS-1year","description":"2) OS within 1 year after medication based on the evaluation by the independent imaging evaluation committee and the investigator"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"PFS-1 year after the last patient's first dose","description":"3)Based on the researcher's assessment of PFS after 1 year of medication"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"OS-1 year after the last patient's first dose","description":"3)Based on the researcher's assessment of OS after 1 year of medication"}]}
{"nct_id":"NCT04736199","start_date":"2021-02-23","phase":"Phase 3","enrollment":555,"brief_title":"Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer","official_title":"A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide in Addition to Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Men With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)","primary_completion_date":"2024-03-27","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-09-26","last_update":"2021-08-30","description":"The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.","other_id":"21140","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"Male","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically or cytologically confirmed adenocarcinoma of prostate\r\n\r\n          -  Metastatic disease\r\n\r\n          -  Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation\r\n             anti-androgen, but no longer than 12 weeks before randomization\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2\r\n\r\n          -  Adequate bone marrow, liver and renal function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant\r\n             therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide,\r\n             darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17\r\n             enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic\r\n             treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for\r\n             prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent\r\n             10 mg of prednisone/day within 28 days prior to randomization\r\n\r\n          -  Treatment with radiotherapy within 2 weeks before randomization\r\n\r\n          -  Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast\r\n             agent(s)\r\n\r\n          -  Had any of the following within 6 months before randomization: stroke, myocardial\r\n             infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft,\r\n             congestive heart failure (New York Heart Association Class III or IV)\r\n\r\n          -  Uncontrolled hypertension as indicated by a resting systolic BP  160 mmHg or\r\n             diastolic BP  100 mmHg despite medical management\r\n\r\n          -  A gastrointestinal (GI) disorder or procedure which is expected to interfere\r\n             significantly with absorption of study drug\r\n\r\n          -  Any prior malignancy (other than adequately treated basal cell or squamous cell skin\r\n             cancer, superficial bladder cancer, or any other cancer in situ currently in complete\r\n             remission) within 5 years prior to randomization\r\n\r\n          -  Inability to swallow oral medications\r\n      ","sponsor":"Bayer","sponsor_type":"Industry","conditions":"Prostatic Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: Darolutamide (Nubeqa, BAY1841788)","description":"Coated tablet, oral administration"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"Coated tablet matching Darolutamide in appearance, oral administration"},{"intervention_type":"Other","name":"Other: Androgen deprivation therapy (ADT)","description":"Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy"}],"outcomes":[{"outcome_type":"primary","measure":"Radiological progression-free survival (rPFS)","time_frame":"36 months","description":"Time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 55 months","description":"Time from the date of randomization to the date of death from any cause."},{"outcome_type":"secondary","measure":"Time to castration-resistant prostate cancer (CRPC)","time_frame":"Up to 55 months","description":"Time from the date of randomization to the date of first castration resistant event (radiological progression, PSA progression or symptomatic skeletal events, whichever occurs first)."},{"outcome_type":"secondary","measure":"Time to initiation of subsequent antineoplastic therapy","time_frame":"Up to 55 months","description":"Time from the date of randomization to initiation of first subsequent antineoplastic therapy for prostate cancer."},{"outcome_type":"secondary","measure":"Time to PSA progression","time_frame":"Up to 55 months","description":"Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression is defined as a ≥25% increase above the nadir (lowest Screening or baseline) value, which is confirmed by a second value 3 or more weeks later, and an increase in absolute value of ≥ 2 ng/mL above nadir, at least 12 weeks from baseline."},{"outcome_type":"secondary","measure":"PSA undetectable rates (<0.2 ng/mL)","time_frame":"Up to 55 months","description":"The percentage of participants with detectable PSA values (≥0.2 ng/mL) at baseline which become undetectable (<0.2 ng/mL) during the study treatment."},{"outcome_type":"secondary","measure":"Time to pain progression","time_frame":"Up to 55 months","description":"Time from the date of randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline. Pain to be assessed with a patient reported questionaire."},{"outcome_type":"secondary","measure":"Number of participants with adverse events as a measure of safety","time_frame":"Up to 55 months"}]}
{"nct_id":"NCT04704219","start_date":"2021-02-23","phase":"Phase 2","enrollment":152,"brief_title":"Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-B61)","official_title":"A Phase 2, Single-arm, Open-label Clinical Trial of Pembrolizumab Plus Lenvatinib in Participants With First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (nccRCC) (KEYNOTE-B61)","primary_completion_date":"2024-08-16","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-10-22","last_update":"2021-08-30","description":"This study is being performed as a single-arm open-label study in order to rapidly provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with previously untreated advanced/metastatic non-clear cell renal cell carcinoma.","other_id":"3475-B61","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":120,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Must have a histologically-confirmed diagnosis of non-clear cell RCC.\r\n\r\n          2. Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee\r\n             on Cancer )\r\n\r\n          3. Has received no prior systemic therapy for advanced nccRCC. Note: Prior\r\n             neoadjuvant/adjuvant therapy for nccRCC is acceptable if completed >12 months prior to\r\n             allocation\r\n\r\n          4. Male participants agree to use approved contraception during the treatment period for\r\n             at least 5 days after the last dose of study medication, or refrain from heterosexual\r\n             intercourse during this period\r\n\r\n          5. Female participants are not pregnant or breastfeeding, and are not a woman of\r\n             childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during\r\n             the treatment period and for at least 120 days post pembrolizumab, or 30 days post\r\n             lenvatinib, whichever occurs last\r\n\r\n          6. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a\r\n             previously irradiated area are considered measurable if progression has been\r\n             demonstrated in such lesions.\r\n\r\n          7. Has submitted an archival tumor tissue sample or newly obtained core or incisional\r\n             biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded\r\n             (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to\r\n             archived tissue.\r\n\r\n          8. Has Karnofsky Performance Status (KPS) 70% as assessed within 10 days prior to the\r\n             start of study intervention.\r\n\r\n          9. Has adequately controlled blood pressure with or without antihypertensive medications\r\n\r\n         10. Have adequate organ function.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Has collecting duct histology.\r\n\r\n          2. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose\r\n             of study intervention.\r\n\r\n          3. Has a left ventricular ejection fraction below the institutional (or local laboratory)\r\n             normal range\r\n\r\n          4. Has radiographic encasement or invasion of a major blood vessel, or of intratumoral\r\n             cavitation.\r\n\r\n          5. Has clinically significant cardiovascular disease within 12 months from first dose of\r\n             study intervention.\r\n\r\n          6. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other\r\n             condition that might affect the absorption of lenvatinib.\r\n\r\n          7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior\r\n             to the first dose of study drug\r\n\r\n          8. Has had major surgery within 3 weeks prior to first dose of study intervention.\r\n\r\n          9. Has received prior therapy with an anti-programmed cell-death 1 (PD-1),\r\n             anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2\r\n             (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell\r\n             receptor (e.g., CTLA-4, OX-40, CD137).\r\n\r\n         10. Has received prior systemic anticancer therapy including investigational agents within\r\n             4 weeks prior to allocation.\r\n\r\n         11. Has received prior radiotherapy within 2 weeks of start of study intervention.\r\n             Participants must have recovered from all radiation-related toxicities, not require\r\n             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted\r\n             for palliative radiation (2 weeks of radiotherapy) to non-central nervous system\r\n             (CNS) disease.\r\n\r\n         12. Has received a live or attenuated vaccine within 30 days before the first dose of\r\n             study intervention.\r\n\r\n         13. Is currently participating in or has participated in a study of an investigational\r\n             agent or has used an investigational device within 4 weeks prior to the first dose of\r\n             study intervention.\r\n\r\n         14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy\r\n             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior the first dose of study intervention.\r\n\r\n         15. Has a known additional malignancy that is progressing or has required active treatment\r\n             within the past 3 years.\r\n\r\n             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of\r\n             the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that\r\n             have undergone potentially curative therapy are not excluded.\r\n\r\n         16. Has known active CNS metastases and/or carcinomatous meningitis.\r\n\r\n         17. Has severe hypersensitivity (Grade 3) to pembrolizumab, lenvatinib and/or any of\r\n             their excipients.\r\n\r\n         18. Has an active autoimmune disease that has required systemic treatment in past 2 years\r\n\r\n         19. Has a history of (non-infectious) pneumonitis that required steroids or has current\r\n             pneumonitis.\r\n\r\n         20. Has an active infection requiring systemic therapy.\r\n\r\n         21. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is\r\n             required unless mandated by local health authority.\r\n\r\n         22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active\r\n             Hepatitis C virus\r\n\r\n         23. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).\r\n\r\n         24. Has had an allogenic tissue/solid organ transplant.\r\n      ","sponsor":"Merck Sharp & Dohme Corp.","sponsor_type":"Industry","conditions":"Renal Cell Carcinoma","interventions":[{"intervention_type":"Biological","name":"Biological: Pembrolizumab","description":"Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation"},{"intervention_type":"Drug","name":"Drug: Lenvatinib","description":"Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation."}],"outcomes":[{"outcome_type":"primary","measure":"Objective Response Rate (ORR)","time_frame":"Up to approximately 2 years","description":"Objective Response Rate (ORR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by blinded independent central review (BICR)."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Up to approximately 2 years","description":"Duration of Response (DOR) is defined for participants who demonstrate confirmed CR or PR as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Progression-free Survival (PFS)","time_frame":"Up to approximately 2 years","description":"Progression-free Survival (PFS) is defined as the time from the date of first dose to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Up to approximately 2 years","description":"Overall Survival (OS) is defined as the time from date of first dose until death from any cause."},{"outcome_type":"secondary","measure":"Clinical Benefit Ratio (CBR)","time_frame":"Up to approximately 2 years","description":"Clinical Benefit Ratio (CBR) is defined as the percentage of participants who achieved CR, PR, or stable disease (SD) for at least 6 months per RECIST 1.1 by BICR."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Up to approximately 2 years","description":"Disease Control Rate (DCR) is defined as the percentage of participants who achieved CR, PR, or SD per RECIST 1.1 by BICR."},{"outcome_type":"secondary","measure":"Number of Participants Who Experienced One or More Adverse Events (AEs)","time_frame":"Up to approximately 2 years","description":"An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study."},{"outcome_type":"secondary","measure":"Number of Participants Who Discontinued Study Medication Due to an AE","time_frame":"Up to approximately 2 years","description":"An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study."}]}
{"nct_id":"NCT04677504","start_date":"2021-02-23","phase":"Phase 2","enrollment":150,"brief_title":"A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer","official_title":"A Phase II, Randomized, Double-Blind Placebo-Controlled Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer","primary_completion_date":"2023-02-21","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-04-24","last_update":"2021-09-14","description":"This study will evaluate the efficacy and safety of atezolizumab with bevacizumab in combination with cisplatin and gemcitabine(CisGem), compared with atezolizumab in combination with CisGem, in participants with advanced biliary tract cancer (BTC) who have not received prior systemic therapy. Treatment will consist of a chemotherapy combination phase followed by a cancer immunotherapy (CIT)/placebo phase.","other_id":"GO42661","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Double","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Considered to be eligible to receive platinum-based chemotherapy, in the\r\n             investigator's judgment\r\n\r\n          -  Documentation of recurrent/metastatic or locally advanced unresectable disease based\r\n             on computed tomography (CT) or magnetic resonance imaging (MRI) scans\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of iCCA, eCCA, or GBC\r\n\r\n          -  No prior systemic therapy for advanced BTC\r\n\r\n          -  At least one measurable untreated lesion (per RECIST v1.1)\r\n\r\n          -  Adequate biliary drainage with no evidence of ongoing infection\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1\r\n\r\n          -  Life expectancy of > 3 months\r\n\r\n          -  Adequate hematologic and end-organ function\r\n\r\n          -  For women of childbearing potential: agreement to remain abstinent (refrain from\r\n             heterosexual intercourse) or use contraceptive methods, and agreement to refrain from\r\n             donating eggs\r\n\r\n          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use\r\n             a condom, and agreement to refrain from donating sperm\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Recurrent disease <=6 months after curative surgery or <= 6 months after the\r\n             completion of adjuvant therapy\r\n\r\n          -  Prior local regional therapy such as radioembolization\r\n\r\n          -  Combined or mixed hepatocellular/cholangiocarcinoma\r\n\r\n          -  Clinically significant hepatic encephalopathy within the 12 months prior to Day 1 of\r\n             Cycle 1\r\n\r\n          -  National Cancer Institute Common Terminoogy Criteria for Adverse Events Grade >= 2\r\n             peripheral neuropathy\r\n\r\n          -  Prior bleeding event due to untreated or incompletely treated esophageal and/or\r\n             gastric varices within 6 months prior to Day 1 of Cycle 1\r\n\r\n          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within\r\n             5 months after the final dose of atezolizumab or within 6 months after the final dose\r\n             of bevacizumab, cisplatin or gemcitabine\r\n\r\n          -  Active or history of autoimmune disease or immune deficiency\r\n\r\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced\r\n             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening\r\n             chest computed tomography scan\r\n\r\n          -  History of malignancy other than BTC within 5 years prior to screening, with the\r\n             exception of malignancies with a negligible risk of metastasis or death\r\n\r\n          -  Symptomatic, untreated, or actively progressing CNS metastases\r\n\r\n          -  For patients with lung metastases, if one of the following criteria applies: Large,\r\n             centrally located pulmonary metastases; Clear tumor infiltration into the thoracic\r\n             great vessels seen on imaging; Clear cavitation of pulmonary lesions seen on imaging\r\n\r\n          -  Active tuberculosis\r\n\r\n          -  Co-infection with HBV and HCV\r\n\r\n          -  Treatment with systemic immunostimulatory agents or immunosuppressive medication\r\n\r\n          -  Inadequately controlled arterial hypertension\r\n\r\n          -  History of hypertensive crisis or hypertensive encephalopathy\r\n\r\n          -  Significant vascular disease\r\n\r\n          -  Evidence of bleeding diathesis or significant coagulopathy\r\n\r\n          -  Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture\r\n\r\n          -  Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)\r\n\r\n          -  Preexisting renal impairment, myelosuppression, or hearing impairment\r\n      ","sponsor":"Hoffmann-La Roche","sponsor_type":"Industry","conditions":"Biliary Tract Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Atezolizumab","description":"Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Bevacizumab","description":"Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab."},{"intervention_type":"Other","name":"Other: Placebo","description":"Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab."},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Cisplatin will be administered intravenously at a dose of 25 mg/m^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8."},{"intervention_type":"Drug","name":"Drug: Gemcitabine","description":"Gemcitabine will be administered intravenously at a dose of 1000 mg/m^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8."}],"outcomes":[{"outcome_type":"secondary","measure":"Prevalence of ADAs to Atezolizumab","time_frame":"Baseline"},{"outcome_type":"secondary","measure":"Incidence of ADAs to Atezolizumab","time_frame":"At pre-defined intervals from administration of study drug up to approximately 3-5 years"},{"outcome_type":"primary","measure":"Progression Free Survival (PFS)","time_frame":"Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximatly 3-5 years)","description":"PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)"},{"outcome_type":"secondary","measure":"Overall Survival (OS)","time_frame":"Randomization to death from any cause (up to approximately 3-5 years)","description":"OS, defined as the time from randomization to death from any cause."},{"outcome_type":"secondary","measure":"Confirmed Objective Response Rate (ORR)","time_frame":"Randomization up to approximately 3-5 years","description":"Confirmed ORR, defined as the proportion of participants with CR or PR on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"First occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 3-5 years)","description":"DOR, defined as the time from the first occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR)","time_frame":"Randomization up to approximately 3-5 years","description":"DCR, defined as the proportion of patients with a CR or a PR on two consecutive occasions >= 4 weeks apart or SD with a minimum duration of 9weeks, as determined by the investigator according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Time to Confirmed Deterioration (TTCD)","time_frame":"Randomization to the first clinically meaningful deterioration (up to approximately 3-5 years)","description":"TTCD in patient-reported physical functioning, role functioning, and quality of life, as measured by the respective scales of the EORTC QLQ-C30 and/or EORTC IL77, and defined as the time from randomization to the first clinically meaningful deterioration that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks."},{"outcome_type":"secondary","measure":"Percentage of Participants With Adverse Events","time_frame":"Randomization up to approximately 3-5 years"},{"outcome_type":"secondary","measure":"Serum Concentration of atezolizumab","time_frame":"At pre-defined intervals from administration of study drug up to approximately 3-5 years","description":"Serum concentration of atezolizumab at specified timepoints."}]}
{"nct_id":"NCT04697628","start_date":"2021-02-22","phase":"Phase 3","enrollment":482,"brief_title":"Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer","official_title":"A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs Investigator's Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer","primary_completion_date":"2024-05-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-05-31","last_update":"2021-09-21","description":"This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent). Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of four different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.","other_id":"SGNTV-003","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria\r\n\r\n          -  Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or\r\n             adenosquamous histology, and:\r\n\r\n          -  Has experienced disease progression during or after treatment with a standard of care\r\n             systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as\r\n             either:\r\n\r\n               -  paclitaxel+cisplatin+bevacizumab, or\r\n\r\n               -  paclitaxel+carboplatin+bevacizumab, or\r\n\r\n               -  paclitaxel+topotecan/nogitecan+bevacizumab\r\n\r\n          -  Note: In cases where bevacizumab is not a standard of care therapy or the participant\r\n             is ineligible for bevacizumab treatment according to local standards, prior treatment\r\n             with bevacizumab is not required.\r\n\r\n          -  Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic\r\n             cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or\r\n             in combination with radiation therapy, should not be counted as a systemic therapy\r\n             regimen. Single agent therapy with pembrolizumab for r/mCC cancer should be counted.\r\n\r\n          -  Measurable disease according to RECIST v1.1 as assessed by the investigator.\r\n\r\n          -  Has ECOG performance status of 0 or 1 prior to randomization.\r\n\r\n          -  Has life expectancy of at least 3 months.\r\n\r\n        Exclusion Criteria\r\n\r\n          -  Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned\r\n             as part of the inclusion criteria above.\r\n\r\n          -  Has clinically significant bleeding issues or risks. This includes known past or\r\n             current coagulation defects leading to an increased risk of bleeding; diffuse alveolar\r\n             hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma\r\n             with increased risk of life-threatening bleeding or history of severe head trauma or\r\n             intracranial surgery within 8 weeks of trial entry.\r\n\r\n          -  Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or\r\n             stroke (transient ischemic attack >1 month prior to screening is allowed).\r\n\r\n          -  Active ocular surface disease or a history of cicatricial conjunctivitis or\r\n             inflammatory conditions that predispose to cicatrizing conjunctivitis (e.g. Wagner\r\n             syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular\r\n             Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and\r\n             participants with penetrating ocular transplants. Cataracts alone is not an exclusion\r\n             criterion.\r\n\r\n          -  Major surgery within 4 weeks or minor surgery within 7 days prior to the first study\r\n             treatment administration.\r\n\r\n          -  Peripheral neuropathy grade 2.\r\n\r\n          -  Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs.\r\n\r\n        There are additional inclusion and exclusion criteria. The study center will determine if\r\n        criteria for participation are met.\r\n      ","sponsor":"Seagen Inc.","sponsor_type":"Industry","conditions":"Cervical Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: tisotumab vedotin","description":"2.0 mg/kg every 3 weeks (Q3W)"},{"intervention_type":"Drug","name":"Drug: topotecan","description":"1 or 1.25 mg/m2 intravenous (IV) on Days 1 to 5, every 21 days"},{"intervention_type":"Drug","name":"Drug: vinorelbine","description":"30 mg/m2 IV on Days 1 and 8, every 21 days"},{"intervention_type":"Drug","name":"Drug: gemcitabine","description":"1000 mg/m2 IV on Days 1 and 8, every 21 days"},{"intervention_type":"Drug","name":"Drug: irinotecan","description":"100 or 125 mg/m2 IV weekly for 28 days, every 42 days"},{"intervention_type":"Drug","name":"Drug: pemetrexed","description":"500 mg/m2 IV on Day 1, every 21 days"}],"outcomes":[{"outcome_type":"secondary","measure":"Confirmed objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator","time_frame":"Up to approximately 6 months","description":"Confirmed objective response rate is defined as the proportion of participants with a confirmed CR or partial response (PR) per RECIST v.1.1."},{"outcome_type":"primary","measure":"Overall survival (OS)","time_frame":"Up to approximately 2 years","description":"OS is defined as the time from the date of randomization to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator","time_frame":"Up to approximately 1 year","description":"PFS per investigator is defined as the time from the date of randomization to the first documentation of disease progression per RECIST v.1.1 by the investigator, or to date of death due to any cause, whichever occurs earlier."},{"outcome_type":"secondary","measure":"Time-to-response (TTR) as assessed by the investigator","time_frame":"Up to approximately 6 months","description":"TTR will be summarized descriptively by treatment group using the Kaplan-Meier approach. Only participants with confirmed complete response (CR) or partial response (PR) will be included in the analysis."},{"outcome_type":"secondary","measure":"Duration of response (DOR) as assessed by the investigator","time_frame":"Up to approximately 1 year","description":"DOR will be summarized descriptively by treatment group using the Kaplan-Meier approach. Only participants with confirmed CR or PR will be included in the analysis."},{"outcome_type":"secondary","measure":"Incidence of adverse events (AEs)","time_frame":"Up to approximately 2 years","description":"Analyses of AEs will be summarized descriptively"},{"outcome_type":"secondary","measure":"Health-related quality of life as assessed by EQ-5D-5L index","time_frame":"Up to approximately 2 years","description":"EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression."},{"outcome_type":"secondary","measure":"Health-related quality of life as assessed by EQ-5D visual analog scale (VAS)","time_frame":"Up to approximately 2 years","description":"EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The EQ VAS records the participant's self-rated health on a vertical VAS. This can be used as a quantitative measure of health outcome that reflects the participant's own judgment."},{"outcome_type":"secondary","measure":"Health-related quality of life as assessed by EORTC-QLQ-C30","time_frame":"Up to approximately 6 months","description":"The QLQ-C30 is a validated questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess the quality of life of participants with cancer in multicultural clinical research settings."},{"outcome_type":"secondary","measure":"Health-related quality of life as assessed by EORTC-QLQ-CX24","time_frame":"Up to approximately 6 months","description":"The EORTC-QLQ-CX24 is a validated questionnaire developed by the EORTC to assess the quality of life in patients who are treated for cervical cancer both in clinical studies and in clinical practice."}]}
{"nct_id":"NCT04688931","start_date":"2021-02-19","phase":"Phase 3","enrollment":632,"brief_title":"A Phase 3 Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer","official_title":"A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (LG IR NMIBC)","primary_completion_date":"2023-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-31","last_update":"2021-07-02","description":"This is a global, randomized, controlled, open-label Phase 3 study designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without () transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC).","other_id":"BL006","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Capable of giving signed informed consent which includes compliance with the\r\n             requirements and restrictions listed in the informed consent form (ICF) and in the\r\n             protocol.\r\n\r\n          2. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by\r\n             cold cup biopsy at screening or within 8 weeks of screening.\r\n\r\n          3. Is at intermediate risk for progression, defined as having 1 or 2 of the following:\r\n\r\n               -  Presence of multiple tumors;\r\n\r\n               -  Solitary tumor > 3 cm;\r\n\r\n               -  Recurrence ( 1 occurrence of LG NMIBC within 1 year of the current diagnosis).\r\n\r\n          4. Negative voiding cytology for high grade (HG) disease within 6 weeks of screening.\r\n\r\n          5. Has adequate organ and bone marrow function as determined by the following routine\r\n             laboratory tests:\r\n\r\n               -  Leukocytes  3,000 cells per L;\r\n\r\n               -  Absolute neutrophil count  1,500 cells per L;\r\n\r\n               -  Platelets  100,000 per L;\r\n\r\n               -  Hemoglobin  9.0 g/dL;\r\n\r\n               -  Total bilirubin  1.5 x upper limit of normal (ULN);\r\n\r\n               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)  2.5  ULN;\r\n\r\n               -  Alkaline phosphatase (ALP)  2.5  ULN;\r\n\r\n               -  Estimated glomerular filtration rate (eGFR)  30 mL/min.\r\n\r\n          6. Has no evidence of active urinary tract infection (UTI).\r\n\r\n          7. Contraceptive use by men and women should be consistent with local regulations\r\n             regarding the methods of contraception for clinical study participants. Women of\r\n             childbearing potential (defined as premenopausal women who have not been sterilized),\r\n             including female patients and female partners of male patients, must be willing to use\r\n             2 acceptable forms of effective contraception from enrollment through 6 months\r\n             post-treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of\r\n             enrollment.\r\n\r\n          2. Received Bacillus Calmette-Gurin (BCG) treatment for urothelial carcinoma (UC) within\r\n             previous 1 year.\r\n\r\n          3. History of HG papillary UC in the past 2 years.\r\n\r\n          4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be\r\n             readily managed.\r\n\r\n          5. Clinically significant urethral stricture that would preclude passage of a urethral\r\n             catheter.\r\n\r\n          6. History of pelvic radiotherapy.\r\n\r\n          7. History of:\r\n\r\n               -  Neurogenic bladder;\r\n\r\n               -  Active urinary retention;\r\n\r\n               -  Any other condition that would prohibit normal voiding.\r\n\r\n          8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper\r\n             tract UC.\r\n\r\n          9. Current tumor grading of T1.\r\n\r\n         10. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of\r\n             the investigator, the patient would be unable to comply with the protocol.\r\n\r\n         11. History of prior treatment with an intravesical chemotherapeutic agent except for a\r\n             single dose of chemotherapy immediately post any previous TURBT.\r\n\r\n         12. Has previously participated in a study in which they received UGN-102.\r\n\r\n         13. Has participated in a study with an investigational agent or device within 30 days of\r\n             randomization.\r\n      ","sponsor":"UroGen Pharma Ltd.","sponsor_type":"Industry","conditions":"Bladder Cancer|Urothelial Carcinoma|Urothelial Carcinoma Bladder","interventions":[{"intervention_type":"Procedure","name":"Procedure: TURBT","description":"The current standard of care for treatment of LG IR NMIBC is TURBT under general anesthesia."},{"intervention_type":"Drug","name":"Drug: UGN-102","description":"UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder."}],"outcomes":[{"outcome_type":"primary","measure":"Disease-free survival (DFS)","time_frame":"Up to 24 months","description":"DFS is defined the same way in both treatment groups, however, it is defined differently for patients who have a CR or NCR at the 3-month disease assessment. For patients who have a CR at 3 months, DFS is defined as the time from randomization to the earliest date of disease recurrence or death due to any cause. Patients who have a NCR at 3 months will be treated with TURBT in both treatment groups and DFS is defined as the time from this TURBT to the earliest date of disease recurrence or death due to any cause."},{"outcome_type":"secondary","measure":"Time to recurrence (TTR)","time_frame":"Up to 24 months","description":"TTR is defined the same way in both treatment groups, however, it is defined differently for patients who have a CR or NCR at the 3-month disease assessment. For patients who have a CR at 3 months, TTR is defined as the time from randomization to the first documented disease recurrence. Patients who have a NCR at 3 months will be treated with TURBT in both treatment groups and TTR is defined as the time from this TURBT to the first documented disease recurrence."},{"outcome_type":"secondary","measure":"Complete response rate (CRR)","time_frame":"3 months","description":"CRR is defined as the percentage of patients who achieve CR at the 3-month disease assessment."},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"Up to 24 months","description":"DOR is defined as the time from first documented CR to the date of first documented disease recurrence or death due to any cause among patients who achieve CR at the 3-month disease assessment."},{"outcome_type":"secondary","measure":"Observed CRR at scheduled disease assessment timepoint","time_frame":"Up to 24 months","description":"Observed CRR at scheduled disease assessment timepoint is defined as the percentage of patients who achieve CR at the 3-month disease assessment and maintain CR up to a particular follow-up disease assessment."},{"outcome_type":"secondary","measure":"Incidence of TURBT","time_frame":"Up to 24 months","description":"Incidence of TURBT is defined as the percentage of patients requiring TURBT and the average number of TURBTs per patient in each treatment group."},{"outcome_type":"secondary","measure":"Changes from baseline in health-related quality of life","time_frame":"Up to 24 months","description":"The European Organisation for Research and Treatment of Cancer (EORTC) 24-item quality of life questionnaire for patients with NMIBC (QLQ-NMIBC24) is a patient-reported instrument that assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual intimacy, risk of contaminating partner, male sexual problems, female sexual problems, sexual function, and sexual enjoyment).\r\nDescriptive statistics will be used to summarize the scored scales for each of the domains and the change from baseline in the domain scores at each scheduled assessment time point."},{"outcome_type":"secondary","measure":"Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology, serum chemistry, and urinalysis).","time_frame":"Up to 24 months","description":"The percentage of patients with each type of event will be summarized."}]}
{"nct_id":"NCT04721015","start_date":"2021-02-18","phase":"Phase 1","enrollment":109,"brief_title":"Study of Intravenous (IV) ABBV-637 Alone or in Combination With IV Docetaxel/Osimertinib to Assess Adverse Events and Change in Disease Activity in Adult Participants With Relapsed/Refractory (R/R) Solid Tumors","official_title":"A Phase 1 First In Human Study Evaluating Safety And Efficacy Of ABBV-637 As Either Monotherapy Or In Combination In Adult Subjects With Relapsed And Refractory Solid Tumors","primary_completion_date":"2025-11-25","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-11-28","last_update":"2021-07-30","description":"Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to evaluate the safety and efficacy (how well the study drug works against the disease) of ABBV-637 alone or in combination with docetaxel/osimertinib in participants with solid tumors (NSCLC). Adverse events and change in disease activity will be assessed. ABBV-637 is an investigational drug being developed for the treatment of solid tumors. Study consists of 3 parts - monotherapy dose escalation (Part 1), combination dose escalation and expansion (Parts 2a and 2b) with docetaxel and combination dose escalation and expansion (Parts 3a and 3b) with osimertinib. Approximately 109 adult participants with relapsed/refractory (R/R) solid tumors will be enrolled in approximately 30 sites across the world. In Part 1, participants with solid tumors will receive intravenous (IV) ABBV-637 in 28-day cycles. In Part 2a and 2b, participants will receive IV ABBV-637 in combination with IV docetaxel in 28-day cycles. In Part 3a and 3b, participants will receive intravenous (IV) ABBV-637 in combination with daily oral tablets of osimertinib in 28 days cycle. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. Treatment effects will be monitored by medical assessments, blood tests, side effect reporting, and questionnaires.","other_id":"M20-111","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologic solid tumor diagnosis (Part 1).\r\n\r\n          -  Participants enrolled in Part 2 and Part 3(combination dose escalation and expansion)\r\n             must have non-small cell lung cancer (NSCLC) epidermal growth factor receptor\r\n             (EGFR)-expressing per central laboratory testing.\r\n\r\n          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.\r\n\r\n          -  For Part 1 only - history of relapsed/refractory (R/R) disease that has progressed on\r\n             all standard of care therapy.\r\n\r\n          -  For Part 2 only - history of RR NSCLC that has progressed after treatment with\r\n             platinum-based chemotherapy regimen and either immune checkpoint inhibitor or targeted\r\n             therapy and may not have been treated with prior single agent chemotherapy.\r\n\r\n          -  For Part 3 only - history of RR NSCLC that has progressed on osimertinib\r\n\r\n          -  Meet the laboratory values as described in the protocol.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  History (within 6 months) of congestive heart failure (defined as New York Heart\r\n             Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia\r\n             requiring pharmacological or surgical intervention, pericardial effusion, or\r\n             pericarditis.\r\n\r\n          -  Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except\r\n             alopecia.\r\n\r\n          -  For Part 3 only: History of interstitial lung disease (ILD) or pneumonitis that\r\n             required treatment with systemic steroids, nor any evidence of active ILD or\r\n             pneumonitis.\r\n      ","sponsor":"AbbVie","sponsor_type":"Industry","conditions":"Advanced Solid Tumors Cancer|Non Small Cell Lung Cancer (NSCLC)","interventions":[{"intervention_type":"Drug","name":"Drug: ABBV-637","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Intravenous (IV) Infusion"},{"intervention_type":"Drug","name":"Drug: Osimertinib","description":"Oral Tablets"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants Experiencing Adverse Events (AEs)","time_frame":"Up to approximately 3 years","description":"An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above."},{"outcome_type":"primary","measure":"Percentage of Participants With Objective Response Rate (ORR) (Part 2 & 3)","time_frame":"Up to approximately 3 years","description":"ORR is defined as the percentage of participants with a confirmed response (CR) or partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Percentage of Participants With Objective Response Rate (ORR) (Part 1)","time_frame":"Up to approximately 3 years","description":"ORR is defined as the percentage of participants with a confirmed response (CR) or partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) for ABBV-637 Administered as Monotherapy (Part 1)","time_frame":"Up to approximately 12 months","description":"DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) for ABBV-637 in Combination With Docetaxel (Part 2 & 3)","time_frame":"Up to approximately 20 months","description":"DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) for ABBV-637 in Combination With Docetaxel (Part 2 & 3)","time_frame":"Up to approximately 20 months","description":"PFS is defined as the time from the first dose of any study drug to a documented radiographic disease progression according to RECIST version 1.1 as determined by the investigator, clinical progression or death from any cause, whichever occurs earlier."},{"outcome_type":"secondary","measure":"Overall Survival (OS) for ABBV-637 in Combination With Docetaxel (Part 2 & 3)","time_frame":"Up to approximately 12 months after last dose of study drug","description":"OS is defined as the time from the first dose of any study drug until death from any cause."}]}
{"nct_id":"NCT04623775","start_date":"2021-02-17","phase":"Phase 2","enrollment":520,"brief_title":"A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)","official_title":"A Phase 2 Randomized Double-blind Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)","primary_completion_date":"2024-02-27","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-09-23","last_update":"2021-08-25","description":"The purpose of this study is to assess the safety profile of nivolumab plus relatlimab in combination with platinum doublet chemotherapy (PDCT) and to determine if nivolumab plus relatlimab in combination with PDCT improves progression free survival (PFS) when compared to nivolumab plus PDCT in participants with previously untreated Stage IV or recurrent non-small cell lung cancer (NSCLC).","other_id":"CA224-104","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous\r\n             (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th\r\n             International Association for the Study of Lung Cancer Classification) or recurrent\r\n             disease following multi-modal therapy for locally advanced disease\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or\r\n             equal to 1 at screening and confirmed prior to randomization\r\n\r\n          -  Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI)\r\n             per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria\r\n\r\n          -  No prior systemic anti-cancer treatment (including epidermal growth factor receptor\r\n             (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for\r\n             advanced or metastatic disease\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Participants with EGFR, ALK, ROS-1, or known B-rapidly accelerated fibrosarcoma\r\n             proto-oncogene (BRAF V600E) mutations that are sensitive to available targeted therapy\r\n\r\n          -  Untreated CNS metastases\r\n\r\n          -  Leptomeningeal metastases (carcinomatous meningitis)\r\n\r\n          -  Concurrent malignancy requiring treatment or history of prior malignancy active within\r\n             2 years prior to randomization (ie, participants with a history of prior malignancy\r\n             are eligible if treatment was completed at least 2 years before randomization and the\r\n             participant has no evidence of disease)\r\n\r\n          -  Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed\r\n             death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti-cytotoxic\r\n             T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug\r\n             specifically targeting T-cell co-stimulation or checkpoint pathways\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Non-small Cell Lunch Cancer|Recurrent Non-small Cell Lung Cancer|Metastatic Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Nivolumab","description":"Specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: Relatlimab","description":"Specified dose on specified days"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy."},{"intervention_type":"Drug","name":"Drug: Cisplatin","description":"Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy."},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy."},{"intervention_type":"Drug","name":"Drug: Nab-Paclitaxel","description":"Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy."},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy."}],"outcomes":[{"outcome_type":"secondary","measure":"Overall response rate (ORR) per RECIST v1.1 by BICR","time_frame":"Up to 21 months","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of Adverse Events (AEs)","time_frame":"Up to 21 months","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of Serious Adverse Events (SAEs)","time_frame":"Up to 21 months","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of select Adverse Events (AEs)","time_frame":"Up to 21 months","description":"Part 2"},{"outcome_type":"primary","measure":"Treatment-related adverse events (TRAEs) leading to discontinuation within 12 weeks after the first dose","time_frame":"Up to 10 months, from first participant's first dose","description":"Part 1"},{"outcome_type":"primary","measure":"Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent clinical review (BICR)","time_frame":"10 months after randomization, up to 21 months","description":"Part 2"},{"outcome_type":"secondary","measure":"Incidence of TRAEs leading to discontinuation","time_frame":"Up to 10 months, 30 days from participant's last dose","description":"Part 1"},{"outcome_type":"secondary","measure":"Incidence of Adverse Events (AEs)","time_frame":"Up to 10 months, 30 days from participant's last dose","description":"Part 1"},{"outcome_type":"secondary","measure":"Incidence of Serious Adverse Events (SAEs)","time_frame":"Up to 10 months, 30 days from participant's last dose","description":"Part 1"},{"outcome_type":"secondary","measure":"Incidence of select Adverse Events (AEs)","time_frame":"Up to 10 months, 30 days from participant's last dose","description":"Part 1"},{"outcome_type":"secondary","measure":"PFS per RECIST v1.1 by BICR in biomarker subgroups","time_frame":"Until progression, up to 21 months","description":"Part 2"}]}
{"nct_id":"NCT04809142","start_date":"2021-02-04","phase":"Phase 3","enrollment":392,"brief_title":"A Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule as Second-line Treatment in Subjects With Advanced Biliary Cancer","official_title":"A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule Versus Chemotherapy as Second-line Treatment in Subjects With Advanced Biliary Cancer","primary_completion_date":"2022-03-18","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-02-01","last_update":"2021-03-22","description":"This study is a randomized, parallel controlled, multicentre phase III clinical trial to evaluate the efficacy and safety of TQB2450 combined with anlotinib versus chemotherapy as second-line treatment in subjects with advanced biliary cancer.","other_id":"TQB2450-III-08","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Histologically or cytologically confirmed biliary adenocarcinoma, including\r\n             intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC) and\r\n             gallbladder cancer (GBC).\r\n\r\n        2.18 years and older,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to\r\n        1; Life expectancy  3 months;Weight 40 kg or BMI 18.5.\r\n\r\n        3. At least one measurable lesion (based on RECIST 1.1). 4. Previous first-line gemcitabine\r\n        or fluorouracil-based combination chemotherapy failed.\r\n\r\n        5.Adequate laboratory indicators. 6. No pregnant or breastfeeding women, and a negative\r\n        pregnancy test. 7. Understood and Signed an informed consent form.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  1. Tumor disease and medical history:\r\n\r\n               1. Has central nervous system metastases (CNS) and/or cancerous meningitis or\r\n                  leptomeningeal carcinomatosis;\r\n\r\n               2. Has other malignant tumors within 5 years;\r\n\r\n               3. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary\r\n                  with blood vessels is unclear;\r\n\r\n               4. Severe bone damage caused by tumor bone metastasis;\r\n\r\n               5. Has uncontrolled and repeated drainage pleural effusion, pericardial effusion,\r\n                  and ascites;\r\n\r\n               6. Partial or complete intestinal obstruction and complete biliary obstruction that\r\n                  cannot be relieved; 2. Previous anti-tumor therapy:\r\n\r\n               1. Has received Anlotinib Hydrochloride Capsules, Bevacizumab Injection, and immune\r\n                  checkpoint inhibitors such as PD-1, PD-L1, and CTLA-4 in prior treatment;\r\n\r\n               2. Have received anti-tumor therapy within 4 weeks before the first administration;\r\n\r\n               3. Unalleviated toxicity  grade 1 due to any previous anticancer therapy;\r\n                  3.Comorbidities and medical history:\r\n\r\n               1. Active hepatitis B or C;\r\n\r\n               2. Kidney abnormalities;\r\n\r\n               3. Abnormal thyroid function;\r\n\r\n               4. Cardiovascular abnormalities;\r\n\r\n               5. Gastrointestinal abnormalities;\r\n\r\n               6. History of immunodeficiency;\r\n\r\n               7. Has risk of bleeding;\r\n\r\n               8. Uncontrollable active bacterial, fungal or viral infections;\r\n\r\n               9. Lung diseases, such as interstitial pneumonia, obstructive lung disease, and\r\n                  history of symptomatic bronchospasm;\r\n\r\n              10. Allergies to the ingredients of the study drug;\r\n\r\n              11. Have a history of neurological or psychiatric disorders\r\n\r\n              12. According to the researcher's point of view, other severe, acute or chronic\r\n                  medical or mental illnesses or laboratory abnormalities that may increase the\r\n                  risks associated with participating in the study, or may interfere with the\r\n                  interpretation of the study results;\r\n\r\n              13. Have a history of pituitary or adrenal dysfunction\r\n\r\n              14. Has received major surgical treatment, open biopsy, or obvious traumatic injury\r\n                  within 28 days before the first administration;\r\n\r\n              15. Long-term unhealed wound or fracture;\r\n\r\n              16. Has drug abuse history that unable to abstain from or mental disorders; 4. Has\r\n                  participated in other clinical trials within 30 days before the study. 5. Has\r\n                  vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first\r\n                  administration.\r\n\r\n                  6. Pregnant or breastfeeding women. 7. According to the judgement of the\r\n                  investigators, there are other factors that may lead to the termination of the\r\n                  study.\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"Advanced Biliary Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TQB2450 Injection","description":"TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle."},{"intervention_type":"Drug","name":"Drug: Anlotinib hydrochloride","description":"Anlotinib capsules 12 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)."},{"intervention_type":"Drug","name":"Drug: Oxaliplatin injection","description":"Oxaliplatin injection 130 mg/m2 administered IV on Day 1 of each week in 3-week cycles;"},{"intervention_type":"Drug","name":"Drug: Capecitabine tablets","description":"Capecitabine tablets total dose 2000 mg/m2, oral twice a day from Day 1-14 of each 3- week cycles;"},{"intervention_type":"Drug","name":"Drug: Gemcitabine hydrochloride injection","description":"Gemcitabine hydrochloride injection administered 1000 mg/m2 IV on Day 1 and Day 8 of each week in 3-week cycles."}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival (OS)","time_frame":"up to 40 weeks","description":"OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"up to 24 weeks","description":"PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Overall response rate (ORR)","time_frame":"up to 24 weeks","description":"Percentage of participants achieving complete response (CR) and partial response (PR)."},{"outcome_type":"secondary","measure":"Disease control rate（DCR）","time_frame":"up to 24 weeks","description":"Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD)."},{"outcome_type":"secondary","measure":"Duration of response（DOR）","time_frame":"up to 24 weeks","description":"The time when the participants first achieved complete or partial remission to disease progression."},{"outcome_type":"secondary","measure":"Progression-free survival at 6 months","time_frame":"up to 6 months","description":"Percentage of participants whose PFS has achieved at least 6 months."},{"outcome_type":"secondary","measure":"Overall survival at 6 months","time_frame":"up to 6 months","description":"Percentage of participants whose OS has achieved at least 6 months."},{"outcome_type":"secondary","measure":"Overall survival at 12 months","time_frame":"up to 12 months","description":"Percentage of participants whose OS has achieved at least 12 months."}]}
{"nct_id":"NCT04796623","start_date":"2021-02-04","phase":"Phase 2","enrollment":120,"brief_title":"A Study of TQB3616 Capsules Combined With Fulvestrant Injection in Subjects With Advanced Breast Cancer","official_title":"A Open-label, Multicenter Phase II Study of TQB3616 Capsules Combined With Fulvestrant Injection in Subjects With HR-positive, HER2-negative Advanced Breast Cancer","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-01-31","last_update":"2021-03-15","description":"This study is a multicenter, open-label, multi-cohort phase II clinical trials to evaluate the efficacy and safety of TQB3616 capsules combined with Fulvestrant injection in subjects with HR-positive and HER2-negative advanced and/or metastatic breast cancer, including Cohort 1 and Cohort 2. Each cohort will enroll 30-60 cases.","other_id":"TQB3616-II-01","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1.Understood and signed an informed consent form. 2.Eastern Cooperative Oncology Group\r\n             (ECOG) performance status of 0 to 1; Life expectancy  3 months. 3.\r\n             Histopathologically confirmed HR positive and HER2 negative advanced or metastatic\r\n             breast cancer. 4.Cohort 1: patients had received 1 line of treatment. 5.Cohort 2:\r\n             patients had not previously received systemic antitumor therapy. 6.Has at least one\r\n             measurable lesion according to RECIST1.1 criteria. 7.Adequate laboratory indicators.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  1. Concomitant disease and medical history:\r\n\r\n               1. Has other malignant tumors within 3 years;\r\n\r\n               2. Has multiple factors affecting oral medication;\r\n\r\n               3. Unalleviated toxicity  grade 1 due to any previous anticancer therapy;\r\n\r\n               4. Has active or uncontrolled severe infections before the first dose;\r\n\r\n               5. Cirrhosis, active hepatitis#\r\n\r\n               6. Have a history of immunodeficiency; 2. Tumor-related symptoms and treatment:\r\n\r\n               1. Has central nervous system metastases (CNS) and/or cancerous meningitis or\r\n                  leptomeningeal carcinomatosis;\r\n\r\n               2. Had received chemotherapy within 3 weeks prior to the first dose, and had\r\n                  received radiotherapy , hormone therapy, or other anti-tumor therapy within 2\r\n                  weeks prior to the first dose;\r\n\r\n               3. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring\r\n                  recurrent drainage procedures.\r\n\r\n                  3. Has known to be allergic to Fulvestrant injection , TQB3616 or any excipient.\r\n\r\n                  4. Has Participated in other clinical trials within 4 weeks before first dose. 5.\r\n                  According to the judgement of the investigators, there are other factors that may\r\n                  lead to the termination of the study.\r\n      ","sponsor":"Chia Tai Tianqing Pharmaceutical Group Co., Ltd.","sponsor_type":"Industry","conditions":"HR-positive, HER2-negative Advanced Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: TQB3616 capsules","description":"TQB3616 capsules 180 mg given orally, once daily in 28-day cycle."},{"intervention_type":"Drug","name":"Drug: Fulvestrant injection","description":"Fulvestrant injection was given at a fixed dose of 500mg on day 1, day 15 of the first cycle and day 1 of each subsequent cycle, and each cycle is 28 days."}],"outcomes":[{"outcome_type":"primary","measure":"Overall response rate (ORR) assessed by investigator","time_frame":"Baseline up to 24 months","description":"ORR defined as percentage of participants achieving complete response (CR) and partial response (PR), recorded from the first dose until the first documented progressive disease (PD) or death from any cause, based on investigator."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"Baseline up to 24 months","description":"PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Baseline up to 24 months]","description":"OS defined as the time from first dose to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive."},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR)","time_frame":"Baseline up to 24 months","description":"Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD)."},{"outcome_type":"secondary","measure":"Duration of Response (DOR)","time_frame":"Baseline up to 24 months","description":"The time when the participants first achieved complete or partial remission to disease progression."}]}
{"nct_id":"NCT04567615","start_date":"2021-02-04","phase":"Phase 2","enrollment":250,"brief_title":"A Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Liver Cancer Who Have Never Been Treated With Immuno-oncology Therapy After Prior Treatment With Tyrosine Kinase Inhibitors","official_title":"A Phase 2, Randomized, Open-label Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Hepatocellular Carcinoma Who Are Naive to IO Therapy But Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073)","primary_completion_date":"2024-06-27","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-07-21","last_update":"2021-07-26","description":"The purpose of this study is to evaluate the effectiveness and safety of relatlimab in combination with nivolumab in participants with advanced liver cancer who have never been treated with immuno-oncology therapy, after prior treatment with tyrosine kinase inhibitor therapy.","other_id":"CA224-073","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\r\n        visit www.BMSStudyConnect.com\r\n\r\n        Key Inclusion Criteria:\r\n\r\n          -  Must have a diagnosis of hepatocellular carcinoma (HCC) based on histological\r\n             confirmation\r\n\r\n          -  Must have advanced/metastatic HCC\r\n\r\n          -  Have to be immunotherapy treatment-naive; no prior immunotherapies are permitted\r\n\r\n          -  Must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\r\n             measurable untreated lesion\r\n\r\n          -  Child-Pugh score of 5 or 6\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 for ECOG\r\n             performance status scale\r\n\r\n        Key Exclusion Criteria:\r\n\r\n          -  Known fibrolamellar HCC, sarcomatoid HCC, combined hepatocellular cholangiocarcinoma\r\n\r\n          -  Prior organ allograft or allogeneic bone marrow transplantation\r\n\r\n          -  No uncontrolled or significant cardiovascular disease\r\n\r\n          -  No active known autoimmune disease\r\n\r\n        Other protocol-defined inclusion/exclusion criteria apply\r\n      ","sponsor":"Bristol-Myers Squibb","sponsor_type":"Industry","conditions":"Hepatocellular Carcinoma|Hepatoma|Liver Cancer, Adult|Liver Cell Carcinoma|Liver Cell Carcinoma, Adult","interventions":[{"intervention_type":"Biological","name":"Biological: Nivolumab","description":"Specified dose on specified days"},{"intervention_type":"Biological","name":"Biological: Relatlimab","description":"Specified dose on specified days"}],"outcomes":[{"outcome_type":"primary","measure":"Overall response rate (ORR) assessed by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1","time_frame":"Up to approximately 2 years"},{"outcome_type":"secondary","measure":"Incidence of Adverse Events (AEs)","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of Serious Adverse Events (SAEs)","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of AEs leading to discontinuation","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of death","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of clinically significant changes in clinical laboratory results: Hematology tests","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests","time_frame":"Up to approximately 2.5 years"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) assessed by BICR per RECIST v1.1","time_frame":"Up to 2 years until progression of disease"},{"outcome_type":"secondary","measure":"Duration of response (DOR) assessed by BICR per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"Progression-free survival assessed by BICR per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"ORR assessed by investigator per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"DCR assessed by investigator per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"DOR assessed by investigator per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"PFS assessed by investigator per RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 3 years after first dose of treatment"},{"outcome_type":"secondary","measure":"Dose: participant's actual dose as treated","time_frame":"Up to 8 weeks"},{"outcome_type":"secondary","measure":"Response: participant's best overall response (BOR) assessed by BICR using RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"},{"outcome_type":"secondary","measure":"LAG-3 expression by Immunohistochemistry (IHC): participant's actual LAG-3 expression value dichotomized into ≥ 1% and < 1%","time_frame":"Up to 1 month"},{"outcome_type":"secondary","measure":"Response: participant's BOR assessed by BICR using RECIST v1.1","time_frame":"Up to 2 years after first dose of treatment"}]}
{"nct_id":"NCT04704154","start_date":"2021-02-03","phase":"Phase 2","enrollment":200,"brief_title":"A Trial to Learn Whether Regorafenib in Combination With Nivolumab Can Improve Tumor Responses and How Safe it is for Participants With Solid Tumors","official_title":"A Multi-indication, Single-treatment Arm, Open-label Phase 2 Study of Regorafenib and Nivolumab in Combination in Patients With Recurrent or Metastatic Solid Tumors","primary_completion_date":"2023-07-13","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-12-21","last_update":"2021-09-16","description":"Researchers are looking for a better way to treat people with solid tumors. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works. In this trial, the researchers want to learn about regorafenib taken together with nivolumab in a small number of participants with different types of tumors. These include tumors in the head and neck, the esophagus, the pancreas, the brain, and the biliary tract. The biliary tract includes gall bladder and bile ducts. The trial will include about 200 participants who are at least 18 years old. All of the participants will take 90 mg of regorafenib as a tablet by mouth. The dose of regorafenib can be adjusted up to 120 mg or down to 60 mg by the doctor based on how well a participant tolerates treatment. All of the participants will receive 480 milligrams (mg) of nivolumab through a needle put into a vein (IV infusion). The participants will take treatments in 4-week periods called cycles. They will take regorafenib once a day for 3 weeks, then stop for 1 week. In each cycle, the participants will receive nivolumab one time. These 4-week cycles will be repeated throughout the trial. The participants can take nivolumab and regorafenib until their cancer gets worse, until they have medical problems, or until they leave the trial. The longest nivolumab can be given is up to 2 years. During the trial, the doctors will take pictures of the participants' tumors using CT or MRI and will take blood and urine samples. The doctors will also do physical examinations and check the participants' heart health using an electrocardiogram (ECG). They will ask questions about how the participants are feeling and if they have any medical problems.","other_id":"21136","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed selected recurrent or metastatic solid tumor types that have\r\n             progressed after treatment with standard therapies and for which there are no curative\r\n             intent surgery or chemoradiation.\r\n\r\n          -  Cohort 1: subjects with HNSCC (Head and neck squamous-cell carcinoma) who have not\r\n             received prior PD-1/PD-L1 inhibitor therapy.\r\n\r\n          -  Cohort 2: subjects with HNSCC who have progressed on or after prior systemic therapy,\r\n             at least one of which included a PD-1/PD-L1 inhibitor alone or in combination with\r\n             chemotherapy.\r\n\r\n          -  Cohort 3: subjects with ESCC (Esophageal Squamous Cell Carcinoma) who progressed on or\r\n             after platinum and/or fluoropyrimidine based regimen.\r\n\r\n          -  Cohort 4: subjects with PDAC (Pancreatic ductal adenocarcinoma) who have progressed on\r\n             or after gemcitabine or fluoropyrimidine based regimens.\r\n\r\n          -  Cohort 5: subjects with BTC (Biliary tract carcinoma) (intrahepatic or extrahepatic\r\n             cholangiocarcinoma or gall bladder cancer) who have progressed on gemcitabine or\r\n             fluoropyrimidine or platinum therapy or a combination of these agents.\r\n\r\n          -  Cohort 6: subjects with Grade IV GBM (Glioblastoma multiforme) or Grade III AA\r\n             (Anaplastic astrocytoma) (World Health Organization [WHO] criteria) with unequivocal\r\n             first progression after surgery followed by radiotherapy and temozolomide.\r\n\r\n          -  Documented HPV (Human papilloma virus) / p16 status for oropharyngeal cancer.\r\n\r\n          -  Capable of giving signed informed consent, including compliance with the requirements\r\n             and restrictions listed in the informed consent form (ICF) and in the protocol.\r\n\r\n          -  Adult participants of legal maturity (18 years or older).\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1.\r\n\r\n          -  Adequate hematologic and organ function as assessed by the following laboratory tests\r\n             performed within 7 d before start of study treatment including:\r\n\r\n               -  Total bilirubin 1.5 x the upper limit of normal (ULN). Total bilirubin (3 x\r\n                  ULN) is allowed if Gilbert's syndrome is documented\r\n\r\n               -  Alanine transaminase (ALT) and aspartate aminotransferase (AST) 3 x ULN (5 x\r\n                  ULN for participants with liver involvement of their cancer)\r\n\r\n          -  Measurable disease by baseline CT or MRI per RECIST 1.1 or RANO.\r\n\r\n          -  Participants must consent to provide recent biopsy/tumor tissue of a primary tumor\r\n             lesion or from metastases (e.g. liver, lung) for HNSCC (IO treated) for Stage 1 and 2\r\n             and in HNSCC (IO nave) cohort for Stage 2.\r\n\r\n          -  Anticipated life expectancy greater than 3 months.\r\n\r\n          -  Be able to swallow and absorb oral tablets.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Presence of symptomatic central nervous system (CNS) metastases, leptomeningeal\r\n             metastases or spinal cord compression. Previously-treated lesions should be stable for\r\n             at least 6 weeks prior to study entry.\r\n\r\n          -  Participants with a condition requiring systemic treatment with either corticosteroids\r\n             (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14\r\n             days of start of study treatment.\r\n\r\n          -  Prior therapy with PD-1/PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)\r\n             inhibitors, or any form of immunotherapy to treat cancer (except cohort 2).\r\n\r\n          -  Cohort 2: More than one prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors, or any\r\n             other form of immunotherapy to treat cancer.\r\n\r\n          -  ESCC:\r\n\r\n               -  patients with apparent tumor invasion on organs located adjacent to the\r\n                  esophageal disease (e.g., the aorta or respiratory tract).\r\n\r\n               -  patients who have previously received taxane agents for recurrent/metastatic\r\n                  cancer.\r\n\r\n          -  GBM/AA\r\n\r\n               -  Primary tumors localized to the brainstem or spinal cord.\r\n\r\n               -  Presence of diffuse leptomeningeal disease or extracranial disease.\r\n\r\n               -  Participants requiring > 4 mg of dexamethasone or biologic equivalent per day to\r\n                  control symptoms related to brain tumor and cerebral edema within 21 days of\r\n                  starting study treatment.\r\n\r\n          -  Participants who have known dMMR/MSI-H cancers or NTRK (tropomyosin receptor kinase)\r\n             fusions.\r\n\r\n          -  Prior therapy with regorafenib.\r\n\r\n          -  Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is\r\n             shorter) of the first dose of study treatment.\r\n\r\n          -  Participants who have permanent discontinuation of PD-1/PD-L1 therapy due to toxicity.\r\n\r\n          -  Arterial thrombotic or embolic events such as cerebrovascular accident (including\r\n             transient ischemic attacks) within 6 months before the start of study treatment.\r\n             Active pulmonary emboli or deep vein thrombosis that are significant or not adequately\r\n             controlled on anticoagulation regimen as per investigator's judgement.\r\n\r\n          -  History of cardiac disorders as defined by:\r\n\r\n               -  Congestive heart failure  New York Heart Association (NYHA) class 2:\r\n\r\n               -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the\r\n                  last 3 months), myocardial infarction less than 6 months before start of study\r\n                  drug.\r\n\r\n               -  Uncontrolled cardiac arrhythmias.\r\n\r\n          -  Poorly controlled hypertension, defined as a blood pressure consistently above 140/90\r\n             mmHg despite optimal medical management.\r\n\r\n          -  Participants with an active, known or suspected autoimmune disease.\r\n\r\n          -  History of (non-infectious) pneumonitis that required steroids, current pneumonitis or\r\n             interstitial lung disease.\r\n\r\n          -  Active infection > NCI-CTCAE Grade 2.\r\n\r\n          -  Positive test (from historical data or tested during screening) for human\r\n             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\r\n\r\n          -  Any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV)\r\n             indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia\r\n             antigen) positive (except for participants on anti-viral therapy for HBV with a viral\r\n             load < 100 IU/mL), or Hepatitis C antibody (anti-HCV) positive (except if\r\n             HCV-ribonucleic acid [RNA] negative).\r\n\r\n          -  Pregnancy or breast feeding.\r\n\r\n          -  Known hypersensitivity to any of the study drugs, study drug classes, or excipients in\r\n             the formulation.\r\n\r\n          -  History or current evidence of any condition, therapy, or laboratory abnormality that\r\n             might confound the results of the trial or interfere with the participation for the\r\n             full duration of the trial.\r\n\r\n          -  Participants with a current or past history of interstitial lung disease or pulmonary\r\n             fibrosis diagnosed based on imaging or clinical findings.\r\n      ","sponsor":"Bayer","sponsor_type":"Industry","conditions":"Solid Tumors","interventions":[{"intervention_type":"Drug","name":"Drug: Regorafenib, (Stivarga, BAY73-4506)","description":"Intake orally, starting with 3x 30 mg tablets every day (once daily.) for 21 days of every 28-day cycle (21 days on, 7 days off).\r\nIf the starting dose is well tolerated dose can be escalated to 120 mg (4x30 mg tablets)."},{"intervention_type":"Drug","name":"Drug: Nivolumab (Opdivo)","description":"480 mg administered on Day 1 of each treatment cycle."}],"outcomes":[{"outcome_type":"primary","measure":"Overall response rate (ORR)","time_frame":"Up to the last participant having been followed for approximately 10 months, summing up to approximately 2.5 years","description":"Per Response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by local assessment for all solid tumors except GBM/AA (Glioblastoma multiforme/Anaplastic astrocytoma)\r\nPer Response assessment in neuro-oncology (RANO) by local assessment for GBM/AA"},{"outcome_type":"secondary","measure":"Duration of response (DOR)","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years"},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years"},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years"},{"outcome_type":"secondary","measure":"6 months PFS","time_frame":"6 months"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years"},{"outcome_type":"secondary","measure":"1 year OS","time_frame":"1 year"},{"outcome_type":"secondary","measure":"Severity of AEs (adverse events) per CTCAE v 5.0","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years","description":"CTCAE: Common terminology criteria for adverse events"},{"outcome_type":"secondary","measure":"Number of participants with adverse events","time_frame":"From first dosing up to the end of the study (LPLV), summing up to approximately 4 years"}]}
{"nct_id":"NCT04696055","start_date":"2021-02-03","phase":"Phase 2","enrollment":119,"brief_title":"Regorafenib Plus Pembrolizumab in Patients With Advanced or Spreading Liver Cancer Who Have Been Previously Treated With PD-1/PD-L1 Immune Checkpoint Inhibitors","official_title":"An Open-Label Study of Regorafenib in Combination With Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC) After PD1/PD-L1 Immune Checkpoint Inhibitors","primary_completion_date":"2022-11-05","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-10-31","last_update":"2021-09-05","description":"Researchers are looking for a better way to treat people suffering from liver cancer which may have spread to nearby tissue and is unlikely to be cured or controlled with treatment (advanced metastatic hepatocellular carcinoma, HCC). Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works. In this trial, the researchers will learn more about the trial treatment, regorafenib, in a small number of participants. They will study the results when the trial treatment is taken with another cancer treatment called pembrolizumab. There will be 2 parts to this trial. The part 1 (pilot phase) will include about 52 men and women. The part 2 (expansion phase) will include about 67 men and women. All of the participants will have HCC and will be aged 18 years or older. All of the participants will have tried other treatments that did not help their HCC. These other treatments (PD-1/PD-L1 Immune Checkpoint Inhibitors) are designed to work by stopping the activity of certain proteins in the immune system thought to play a role in HCC. During both parts of the trial, the participants will take regorafenib and receive pembrolizumab. In the pilot phase, there will be 2 groups of participants. The group that each participant joins will be based on the treatment they already received for their HCC. The researchers will review the results in each group to learn if regorafenib and pembrolizumab are helping one group of participants more than others. Outcome of this review will determine the population to be treated in the expansion phase.","other_id":"21469","allocation":"N/A","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -   18 years of age on the day of signing informed consent.\r\n\r\n          -  Histological or cytological confirmation of HCC or non-invasive diagnosis of HCC as\r\n             per American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic\r\n             participants.\r\n\r\n          -  Unresectable advanced HCC eligible for systemic therapy.\r\n\r\n          -  Participants must have progressed after only one prior line of systemic immunotherapy\r\n             treatment with an anti-PD-1/PD-L1 mAb administered either as monotherapy or in\r\n             combination with other checkpoint inhibitors or other therapies. A wash out period of\r\n             at least 28 days or 5 half-lives, whichever is shorter, must be completed for\r\n             eligibility in this trial. PD-1/PD-L1 treatment progression is defined by meeting all\r\n             of the following criteria:\r\n\r\n               1. Has received at least 2 doses of an approved anti PD-1/PD-L1 mAb or received\r\n                  PD-1/PD-L1 treatment for 8 weeks, whichever is longer.\r\n\r\n               2. Has demonstrated disease progression after PD-1/PD-L1 treatment as defined by\r\n                  RECIST 1.1. In the absence of rapid clinical progression, the initial evidence of\r\n                  RECIST 1.1 disease progression is to be confirmed using iRECIST by a second\r\n                  assessment no less than four weeks from the date of the first documented\r\n                  progressive disease.\r\n\r\n             i. This determination is made by the investigator. Once progressive disease is\r\n             confirmed, the initial date of RECIST 1.1 progressive disease documentation will be\r\n             considered that date of disease progression.\r\n\r\n        ii. In cases of unequivocal clinical or radiological progression, disease progression\r\n        confirmation may not be required after documented discussion and approval by the sponsor.\r\n\r\n        c. Progressive disease has been documented within 12 weeks from the last dose of\r\n        anti-PD-1/PD-L1 mAb.\r\n\r\n        - Participants who receive anti-PD-1 therapy as adjuvant treatment following complete\r\n        resection of liver cancer and have disease recurrence (unresectable locoregional disease or\r\n        distant metastases) are eligible if they progressed while on active treatment or within 6\r\n        months of stopping anti-PD-1 therapy. This will be considered the first line of systemic\r\n        therapy.\r\n\r\n        For these participants, the following applies:\r\n\r\n          1. a second assessment to confirm disease progression beyond recurrence is not required;\r\n             and\r\n\r\n          2. they must have received at least 2 prior doses of anti-PD-1/PD-L1 mAb.\r\n\r\n               -  Barcelona Clinic Liver Cancer (BCLC) stage B or C.\r\n\r\n               -  Liver function status should be Child-Pugh (CP) Class A within 7 days prior to\r\n                  the first dose of study intervention. CP status should be calculated based on\r\n                  clinical findings and laboratory results during the screening period.\r\n\r\n               -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\r\n                  within 7 days prior to the first dose of study intervention.\r\n\r\n               -  At least one measurable lesion by CT scan or MRI according to RECIST 1.1. Tumor\r\n                  lesions situated in a previously irradiated area, or in an area subjected to\r\n                  other loco-regional therapy, may be considered measurable if there has been\r\n                  demonstrated progression in the lesion.\r\n\r\n               -  Participants with controlled (treated) hepatitis B virus (HBV) infection will be\r\n                  allowed if they meet the following criteria:\r\n\r\n                    -  Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral\r\n                       load must be less than 500 IU/mL prior to first dose of study intervention.\r\n\r\n                    -  Participants on active HBV therapy with viral loads under 500 IU/ml should\r\n                       stay on the same therapy throughout study treatment.\r\n\r\n                    -  Participants who are anti-HBc (+), negative for HBsAg, negative for\r\n                       anti-HBs, and have an HBV viral load under 500 IU/mL that do not require HBV\r\n                       antiviral prophylaxis.\r\n\r\n               -  Provision of recent tumor tissue (as defined below) is mandatory at screening.\r\n                  Exceptions will be accepted for participants with no recent baseline tumor\r\n                  tissues after documented discussion and approval by the sponsor.\r\n\r\n                    -  Tumor tissue obtained within 180 days of enrollment and after the last dose\r\n                       of most recent anti-cancer therapy.\r\n\r\n                    -  Or a new biopsy.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes.\r\n\r\n          -  Patients with disease that is suitable for local therapy administered with curative\r\n             intent.\r\n\r\n          -  Patients who experienced any Common Terminology Criteria for Adverse Events (CTCAE) \r\n             3 or any other immune- related toxicities that led to permanent discontinuation of\r\n             treatment with immune checkpoint inhibitors in 1 L.\r\n\r\n          -  Persistent proteinuria of CTCAE Grade 3 or higher.\r\n\r\n          -  Diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy\r\n             (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of\r\n             immunosuppressive therapy within 7 days prior to the first dose of study\r\n             interventions.\r\n\r\n          -  Active autoimmune disease.\r\n\r\n          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.\r\n\r\n          -  Any hemorrhage or bleeding event CTCAE Grade  3 within 28 days prior to the start of\r\n             study medication.\r\n\r\n          -  Patients with large esophageal varices at risk of bleeding that are not being treated\r\n             with conventional medical intervention.\r\n\r\n          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident\r\n             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism\r\n             within 6 months before the start of study medication.\r\n\r\n          -  Ongoing infection CTCAE Grade > 2 requiring systemic therapy.\r\n\r\n          -  Dual active HBV infection (HBsAg (+) and / or detectable HBV DNA) and HCV infection\r\n             (anti-HCV Ab (+) and detectable HCV RNA) at study entry.\r\n\r\n          -  Uncontrolled hypertension (systolic blood pressure  140 mmHg or diastolic pressure \r\n             90 mmHg) on more than 2 separate measurements despite optimal medical management.\r\n\r\n          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3\r\n             months).\r\n\r\n          -  Myocardial infarction less than 6 months before start of study intervention.\r\n\r\n          -  Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade  2\r\n             dyspnea).\r\n\r\n          -  Patients with previous malignancies (except non-melanoma skin cancers, and the\r\n             following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or\r\n             breast) are excluded unless a complete remission was achieved at least 3 years prior\r\n             to study entry.\r\n\r\n          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.\r\n             Participants with previously treated brain metastases may participate provided they\r\n             are radiologically stable.\r\n\r\n          -  Significant acute gastrointestinal disorders with diarrhea as a major symptom.\r\n\r\n          -  Prior monotherapy treatment with any tyrosine kinase inhibitor in 1L.\r\n\r\n          -  Prior treatment with regorafenib, in combination regimens with immune checkpoint\r\n             inhibitors.\r\n\r\n          -  Transfusion of blood products within 7 days prior to signing informed consent, or\r\n             administration of colony stimulating factors within 4 weeks prior to signing informed\r\n             consent.\r\n\r\n          -  Previous assignment to treatment during this study.\r\n\r\n          -  Previous (at least a minimum of 28 days, or 5 half-lives of an investigational drug\r\n             before the start of study treatment, whichever is shorter) or concomitant\r\n             participation in another clinical study with investigational medicinal product(s).\r\n      ","sponsor":"Bayer","sponsor_type":"Industry","conditions":"Hepatocellular Carcinoma","interventions":[{"intervention_type":"Drug","name":"Drug: Pembrolizumab","description":"Pembrolizumab 400 mg to be administered as an intravenous (IV) infusion every 6 weeks (Q6W)."},{"intervention_type":"Drug","name":"Drug: Regorafenib (Stivarga, BAY73-4506)","description":"Regorafenib will be given orally (p.o.) at a starting dose of 90 mg QD for 3 weeks of every 4 weeks (i.e., 3 weeks on, 1 week off). If the starting dose of 90 mg daily is well tolerated the dose should be escalated to 120 mg starting after the first 4-week cycle of regorafenib."}],"outcomes":[{"outcome_type":"secondary","measure":"Duration of response (DOR) per RECIST 1.1 by central assessment","time_frame":"Approximately 45 months","description":"DOR is defined as the time (in days) from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death.\r\nRECIST: Response Evaluation Criteria in Solid Tumors"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) per RECIST 1.1 by investigator assessment","time_frame":"Approximately 45 months"},{"outcome_type":"secondary","measure":"Duration of response (DOR) per RECIST 1.1 by investigator assessment","time_frame":"Approximately 45 months"},{"outcome_type":"secondary","measure":"Number of participants with adverse events (AEs)","time_frame":"Approximately 45 months"},{"outcome_type":"secondary","measure":"Number of participants with serious adverse events (SAEs)","time_frame":"Approximately 45 months"},{"outcome_type":"primary","measure":"Objective response rate (ORR) per RECIST 1.1a by central assessment","time_frame":"Approximately 21 months","description":"ORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or partial response (PR).\r\nRECIST: Response Evaluation Criteria in Solid Tumors"},{"outcome_type":"secondary","measure":"Number of participants with safety-relevant changes in clinical parameters","time_frame":"Approximately 45 months"},{"outcome_type":"secondary","measure":"Number of participants with dose modification","time_frame":"Approximately 45 months","description":"Dose modification includes dose interruption, dose reduction, dose discontinuation."}]}
{"nct_id":"NCT04580485","start_date":"2021-02-03","phase":"Phase 1","enrollment":238,"brief_title":"INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors","official_title":"A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors","primary_completion_date":"2023-07-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-07-29","last_update":"2021-08-04","description":"This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, or bladder cancer","other_id":"INCB 106385-102","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Ability to comprehend and willingness to sign an ICF.\r\n\r\n          -  Willing and able to conform to and comply with all Protocol requirements.\r\n\r\n          -  Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian\r\n             cancer, TNBC, CRPC or bladder cancer that progressed after treatment with available\r\n             therapies (including anti PD-(L)1 therapy (if applicable).\r\n\r\n          -  Willingness to undergo pre- and on-treatment tumor biopsy.\r\n\r\n          -  Have CD8 T-cell-positive tumors.\r\n\r\n          -  Presence of measurable disease according to RECIST v1.1.\r\n\r\n          -  ECOG performance status 0 to 1.\r\n\r\n          -  Life expectancy > 12 weeks.\r\n\r\n          -  Willingness to avoid pregnancy or fathering children based.\r\n\r\n          -  Acceptable laboratory parameters\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Clinically significant cardiac disease.\r\n\r\n          -  Known or active CNS metastases and/or carcinomatous meningitis.\r\n\r\n          -  Active or inactive autoimmune disease or syndrome that required systemic treatment in\r\n             the past 2 years or receiving systemic therapy for an autoimmune or inflammatory\r\n             disease..\r\n\r\n          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses\r\n             > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive\r\n             therapy within 7 days before the first dose of study treatment.\r\n\r\n          -  Known additional malignancy that is progressing or requires active treatment,or\r\n             history of other malignancy within 2 years of the first dose of study treatment.\r\n\r\n          -  Has not recovered to  Grade 1 from toxic effects of prior therapy and/or\r\n             complications from prior surgical intervention before starting study treatment.\r\n\r\n          -  Evidence of interstitial lung disease, history of interstitial lung disease, or\r\n             active, noninfectious pneumonitis.\r\n\r\n          -  Immune-related toxicity during prior immune therapy for which permanent\r\n             discontinuation of therapy is recommended, or any immune-related toxicity requiring\r\n             intensive or prolonged immunosuppression to manage.\r\n\r\n          -  Any prior chemotherapy, biological therapy, or targeted therapy to treat the\r\n             participant's disease within 5 half-lives or 28 days (whichever is shorter) before the\r\n             first dose of study treatment.\r\n\r\n          -  Any prior radiation therapy within 28 days before the first dose of study treatment.\r\n\r\n          -  Undergoing treatment with another investigational medication or having been treated\r\n             with an investigational medication within 5 half-lives or 28 days (whichever is\r\n             shorter) before the first dose of study treatment.\r\n\r\n          -  Concomitant treatment with strong CYP3A4 inhibitors or inducers.\r\n\r\n          -  Receipt of a live vaccine within 30 days of the first dose of study treatment.\r\n\r\n          -  Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week\r\n             of the first dose of study treatment.\r\n\r\n          -  Evidence of HBV or HCV infection or risk of reactivation.\r\n\r\n          -  Known history of HIV (HIV 1/2 antibodies).\r\n\r\n          -  History of organ transplant, including allogeneic stem-cell transplantation.\r\n\r\n          -  Known hypersensitivity or severe reaction to any component of study drug(s) or\r\n             formulation components.\r\n\r\n          -  Inability to swallow food or any condition of the upper gastrointestinal tract that\r\n             precludes administration of oral medications.\r\n\r\n          -  Is pregnant or breastfeeding or expecting to conceive or father children within the\r\n             projected duration of the study.\r\n\r\n          -  Any condition that would, in the investigator's judgment, interfere with full\r\n             participation in the study,pose a significant risk to the participant; or interfere\r\n             with interpretation of study data\r\n      ","sponsor":"Incyte Corporation","sponsor_type":"Industry","conditions":"Ovarian Cancer|Bladder Cancer|Non Small Cell Lung Cancer|Squamous Cell Carcinoma of Head and Neck|Triple Negative Breast Cancer|Castration Resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: INCB106385","description":"INCB106385 will be administered orally QD"},{"intervention_type":"Drug","name":"Drug: INCMGA00012","description":"INCMGA0012 will be administered IV once every 4 weeks (Q4W)"}],"outcomes":[{"outcome_type":"secondary","measure":"Cmax of INCB106385 as a single agent or in combination with INCMGA00012","time_frame":"Up to 6 months","description":"Maximum observed plasma concentration."},{"outcome_type":"primary","measure":"Number of treatment-emergent adverse events (TEAE)","time_frame":"Up to Approximately 28 months","description":"Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after last dose of study drug."},{"outcome_type":"secondary","measure":"Tmax of INCB106385 as a single agent or in combination with INCMGA00012","time_frame":"Up to 6 months","description":"Time to maximum plasma concentration"},{"outcome_type":"secondary","measure":"Cmin of INCB106385 as a single agent or in combination with INCMGA00012","time_frame":"Up to 6 months","description":"Minimum observed plasma concentration over the dose interval"},{"outcome_type":"secondary","measure":"AUC of INCB106385 as a single agent or in combination with INCMGA00012","time_frame":"Up to 6 months","description":"Area under the plasma concentration-time curve"},{"outcome_type":"secondary","measure":"CL/F of INCB106385 as a single agent or in combination with INCMGA00012","time_frame":"Up to 6 months","description":"Apparent oral dose clearance"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR)","time_frame":"Up to approximately 24 months","description":"Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Disease Control Rate","time_frame":"Up to approximately 24 months","description":"Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1."},{"outcome_type":"secondary","measure":"Duration Of Response (DOR)","time_frame":"Up to approximately 24 months","description":"Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression."},{"outcome_type":"secondary","measure":"Change in tumoral gene expression","time_frame":"Predose and Week 5-6","description":"Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline"},{"outcome_type":"secondary","measure":"Change in immune cell activation in tumors","time_frame":"Predose and Week 5-6","description":"Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline"}]}
{"nct_id":"NCT04736823","start_date":"2021-02-01","phase":"Phase 2","enrollment":206,"brief_title":"A Trial of AK112 (PD1/VEGF Bispecific) in Combination With Chemotherapy in Patients With NSCLC","official_title":"A Phase II Trial of AK112 (PD1/VEGF Bispecific) in Combination With Chemotherapy in Patients With NSCLC","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-31","last_update":"2021-02-03","description":"This is a phase II study. All patients are stage IIIB/C or IV non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 in combination with chemotherapy in patients with NSCLC.","other_id":"AK112-201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  18 to 75 years old (at the time of inform consent obtained).\r\n\r\n          -  Be able and willing to provide written informed consent and to comply with all\r\n             requirements of study participation (including all study procedures).\r\n\r\n          -  Have histologically- or cytologically-confirmed diagnosis of Stage IIIB/C or IV NSCLC.\r\n\r\n          -  Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from\r\n             either a core or excisional tumor biopsy.\r\n\r\n          -  Have a life expectancy of at least 3 months.\r\n\r\n          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\r\n\r\n          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)\r\n             1.1 assessed by investigator\r\n\r\n          -  Has adequate organ function\r\n\r\n          -  All female and male subjects of reproductive potential must agree to use an effective\r\n             method of contraception, as determined by the Investigator, during and for 120 days\r\n             after the last dose of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Is currently participating in a study of an investigational agent or using an\r\n             investigational device;\r\n\r\n          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2\r\n             years prior to the first dose of study treatment;\r\n\r\n          -  Has undergone major surgery within 30 days prior to the first dose of study treatment;\r\n\r\n          -  Has a known history of prior malignancy except that basal cell carcinoma of the skin,\r\n             squamous cell carcinoma of the skin that has undergone potentially curative therapy or\r\n             in situ cervical cancer\r\n\r\n          -  Has known active central nervous system (CNS) metastases;\r\n\r\n          -  Has carcinomatous meningitis\r\n\r\n          -  Has an active autoimmune disease that has required systemic treatment in the past 2\r\n             years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive\r\n             drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid\r\n             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a\r\n             form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood\r\n             asthma/atopy would be an exception to this rule. Subjects that require intermittent\r\n             use of bronchodilators or local steroid injections would not be excluded from the\r\n             study;\r\n\r\n          -  Has an active infection requiring systemic therapy;\r\n\r\n          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA\r\n             [qualitative] is detected);\r\n\r\n          -  History of myocardial infarction, unstable angina, cardiac or other vascular stenting,\r\n             angioplasty, or surgery within 12 months prior to day 1 of study treatment;\r\n\r\n          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality\r\n             that might confound the results of the study, interfere with the subject's\r\n             participation for the full duration of the study, or is not in the best interest of\r\n             this subject to participate, in the opinion of the treating investigator;\r\n\r\n          -  Has known psychiatric or substance abuse disorders that would interfere with\r\n             cooperation with the requirements of the study\r\n\r\n          -  Has received a live virus vaccine within 30 days prior to first dose of study\r\n             treatment\r\n\r\n          -  Is pregnant, breastfeeding, or expecting to conceive or father a child within the\r\n             projected duration of the study including 120 days following the last dose of study\r\n             treatment.\r\n      ","sponsor":"Akeso","sponsor_type":"Industry","conditions":"NSCLC","interventions":[{"intervention_type":"Drug","name":"Drug: AK112","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"IV infusion"},{"intervention_type":"Drug","name":"Drug: AK105","description":"IV infusion"}],"outcomes":[{"outcome_type":"primary","measure":"ORR (Part 1)","time_frame":"Up to approximately 2 years","description":"ORR is the proportion of subjects with CR or PR , based on RECIST v1.1."},{"outcome_type":"primary","measure":"PFS (Part 2)","time_frame":"Up to approximately 2 years","description":"PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"PFS (Part 1)","time_frame":"Up to approximately 2 years","description":"PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first)."},{"outcome_type":"secondary","measure":"ORR (Part 2)","time_frame":"Up to approximately 2 years","description":"ORR is the proportion of subjects with CR or PR , based on RECIST v1.1."},{"outcome_type":"secondary","measure":"OS","time_frame":"Up to approximately 2 years","description":"OS is the time from the date of randomization or first dosing date to death due to any cause."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Up to approximately 2 years","description":"DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1"}]}
{"nct_id":"NCT04736173","start_date":"2021-02-01","phase":"Phase 3","enrollment":625,"brief_title":"Study to Evaluate Monotherapy Compared to Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer","official_title":"A Phase 3 Study to Evaluate Zimberelimab (AB122) Monotherapy Compared to Standard Chemotherapy or Zimberelimab Combined With AB154 in Front-Line, PD-L1-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer","primary_completion_date":"2025-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-06-30","last_update":"2021-07-19","description":"This Randomized Phase 3 Open-label Study will Evaluate the Efficacy of Zimberelimab (AB122) Monotherapy Compared to Standard Chemotherapy or Zimberelimab Combined with AB154 in Front-Line, PD-L1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer.","other_id":"ARC-10","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Histologically confirmed, squamous or nonsquamous, treatment-naive PD-L1 positive,\r\n             NSCLC that is locally advanced or metastatic without sensitizing epidermal growth\r\n             factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\r\n\r\n          -  Must have at least 1 measurable lesion per RECIST v1.1\r\n\r\n          -  Adequate organ and marrow function\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Presence of any tumor genomic aberration or driver mutation for which a targeted\r\n             therapy is approved by local health authority and available\r\n\r\n          -  Use of any live vaccines against infectious diseases within 28 days of first dose\r\n\r\n          -  Any active autoimmune disease or a documented history of autoimmune disease or\r\n             syndrome that required systemic treatment in the past 2 years (ie, with use of\r\n             disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for\r\n             vitiligo or resolved childhood asthma/atopy.\r\n\r\n          -  Prior malignancy active within the previous 2 years except for locally curable cancers\r\n             that have been apparently cured, such as basal or squamous cell skin cancer,\r\n             superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate\r\n             cancer\r\n\r\n          -  Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an\r\n             immune checkpoint.\r\n      ","sponsor":"Arcus Biosciences, Inc.","sponsor_type":"Industry","conditions":"Non Small Cell Lung Cancer|Nonsquamous Non Small Cell Lung Cancer|Squamous Non-small-cell Lung Cancer|Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Zimberelimab","description":"Zimberelimab is a fully human anti-PD-1 monoclonal antibody"},{"intervention_type":"Drug","name":"Drug: Domvanalimab","description":"Domvanalimab is a humanized monoclonal antibody targeting human TIGIT"},{"intervention_type":"Drug","name":"Drug: Carboplatin","description":"Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve."},{"intervention_type":"Drug","name":"Drug: Pemetrexed","description":"Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve."},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve."}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm A vs. Arm B"},{"outcome_type":"primary","measure":"Progression-free survival (PFS)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm B vs. Arm C - PFS as assessed by RECIST v1.1 by the investigator"},{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm B vs. Arm C"},{"outcome_type":"secondary","measure":"Confirmed Overall response rate (ORR)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm A vs. Arm B - ORR as assessed by RECIST v1.1 by the investigator"},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm A vs. Arm B - PFS as assessed by RECIST v1.1 by the investigator"},{"outcome_type":"secondary","measure":"Confirmed Overall response rate (ORR)","time_frame":"From randomization until death from any cause (up to approximately 7 years)","description":"Arm B vs. Arm C - ORR as assessed by RECIST v1.1 by the investigator"}]}
{"nct_id":"NCT03971110","start_date":"2021-01-28","phase":"Phase 4","enrollment":871,"brief_title":"A Study of Neoadjuvant Hormone Therapy in Patient With Advanced Prostate Cancer Undergoing Radical Prostatectomy.","official_title":"A Multi-centre, Single-arm, Prospective Study to Assess Efficacy and Safety of Neoadjuvant Hormone Therapy Using Zoladex (Goserelin) and Casodex (Bicalutamide) in Patients With Advanced Prostate Cancer Undergoing Radical Prostatectomy.","primary_completion_date":"2022-11-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-11-01","last_update":"2021-09-08","description":"This is A Multi-centre, Single-arm, Prospective, Interventional Study to Assess Efficacy and Safety of Neoadjuvant Hormone Therapy using Zoladex (Goserelin) and Casodex (Bicalutamide) in Patients with Advanced Prostate Cancer Undergoing Radical Prostatectomy, to assess the efficacy by resectability rate of neoadjuvant hormone therapy (NHT) in subjects with advanced prostate cancer.","other_id":"D8664C09827","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Diagnosed within the past 12 months with T2DM according to 1999 WHO criteria\r\n\r\n          2. Men and women aged at least 18 years at screening.\r\n\r\n          3. Either not received oral anti-diabetic drugs or had been on short-term (1 month)\r\n             treatment that had been discontinued 3 months before enrolment.\r\n\r\n          4. HbA1c  7.5% and  10.5% at screening and HbA1c  7.0% and  10.5% at\r\n             pre-randomization visit.\r\n\r\n          5. FPG  13.3 mmol/L ( 240 mg/dL) .\r\n\r\n          6. BMI18.5 kg/m2 and  45.0 kg/m2 .\r\n\r\n          7. C-peptide 0.33nmol/L(1.0 ng/mL).\r\n\r\n          8. Able and willing to provide written informed consent and to comply with the study.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Women who are pregnant, intending to become pregnant during the study period,\r\n             currently lactating females, or women of child-bearing potential not using highly\r\n             effective, medically approved birth control methods.\r\n\r\n          2. Diagnosis or history of:\r\n\r\n               1. Acute metabolic diabetic complications such as ketoacidosis or hyperglycemic\r\n                  hyperosmolar state\r\n\r\n               2. Diabetes insipidus.\r\n\r\n          3. Requirement for insulin therapy. Symptoms of poorly controlled diabetes, including but\r\n             not limited to, marked polyuria and polydipsia with >10% weight loss during the 3\r\n             months before enrollment.\r\n\r\n          4. Triglycerides (fasting) > 9.3 mmol/L (> 800 mg/dL).\r\n\r\n          5. Patients with clinically apparent hepatobiliary disease, including but not limited to\r\n             chronic active hepatitis and/or severe hepatic insufficiency. ALT or AST > 3x upper\r\n             limit of normal (ULN), or serum total bilirubin (TB) >34.2 mol/L (>2 mg/dL).\r\n\r\n          6. Patiens with following renal disease history or renal disease related features:\r\n\r\n               1. History of unstable or rapidly progressing renal disease;\r\n\r\n               2. Patients with moderate /severe renal impairment or end-stage renal disease (eGFR<\r\n                  60 mL/min/1.73 m2)\r\n\r\n               3. Urinary albumin: creatinine ratio >1800 mg/g;\r\n\r\n               4. Serum creatinine (Cr) 133 mol/L (1.50 mg/dL) for male subjects; Serum Cr124\r\n                  mol/L (1.40 mg/dL) for female subjects;\r\n\r\n               5. Conditions of congenital renal glycosuria.\r\n\r\n          7. Severe uncontrolled hypertension defined as SBP 180 mmHg and/or BP 110 mmHg;Patients\r\n             with SBP < 95mmHg.\r\n\r\n          8. Any of the following cardiovascular diseases within 6 months of the enrollment visit:\r\n\r\n               1. Myocardial infarction;\r\n\r\n               2. Cardiac surgery or revascularization (coronary artery bypass graft/percutaneous\r\n                  transluminal coronary angioplasty);\r\n\r\n               3. Unstable angina;\r\n\r\n               4. Congestive heart failure New York Heart Association Class III or IV;\r\n\r\n               5. Transient ischemic attack or significant cerebrovascular disease.\r\n\r\n          9. History of gastrointestinal disease or surgery including Roemheld Syndrome, severe\r\n             hernia, intestinal obstruction, intestinal ulcer, gastroenterostomy, enterectomy,\r\n             bariatric surgery or lap-band procedure.\r\n\r\n         10. Malignancy within 5 years of the enrollment visit (with the exception of treated basal\r\n             cell or treated squamous cell carcinoma).\r\n\r\n         11. Known immunocompromised status, including but not limited to, individuals who had\r\n             undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).\r\n\r\n         12. Any subject who, in the judgment of the investigator, was at risk for dehydration or\r\n             volume depletion that might affect the interpretation of efficacy or safety data.\r\n\r\n         13. History of bone fracture secondary to diagnosed severe osteoporosis.\r\n\r\n         14. Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic,\r\n             endocrine, psychiatric, or rheumatic diseases as judged by the Investigator.\r\n\r\n         15. Replacement or chronic systemic corticosteroid therapy, defined as any dose of\r\n             systemic corticosteroid taken for >4 weeks within 3 months before enrollment visit.\r\n\r\n         16. Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine,\r\n             diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment\r\n             visit.\r\n\r\n         17. Any subject who was currently abusing alcohol or other drugs or had done so within the\r\n             last 6 months\r\n\r\n         18. Donation of blood or blood products, blood transfusion, or participation in a clinical\r\n             study requiring withdrawal of >400 mL of blood during the 6 weeks before the\r\n             enrollment visit\r\n\r\n         19. History of hypersensitivity reaction to dapagliflozin or acarbose. Allergies or\r\n             contraindication to the contents of dapagliflozin tablets or acarbose tablests.\r\n\r\n         20. Previous participation in a clinical trial with dapagliflozin.\r\n\r\n         21. Administration of any other investigational drug within 30 days of planned enrollment\r\n             to this study, or within 5 half-life periods of other investigational drugs.\r\n\r\n         22. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol\r\n             or has any severe concurrent medical or psychological condition that may affect the\r\n             interpretation of efficacy or safety data.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"Advanced Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Zoladex and Casodex","description":"The eligible subjects will receive Casodex 50 mg orally per day in combination with Zoladex 10.8 mg implant subcutaneously as neoadjuvant therapy per 12 weeks for up to 24 weeks."}],"outcomes":[{"outcome_type":"primary","measure":"Resectability rate for primary tumour (the resectability will be assessed by central review using a digital rectal examination and confirmed by CT or MRI)","time_frame":"at 24 week","description":"To assess the efficacy by resectability rate of neoadjuvant hormone therapy (NHT) in subjects with advanced prostate cancer"},{"outcome_type":"secondary","measure":"Radical prostatectomy rate","time_frame":"From baseline to 24 week","description":"Which will be derived using the number of patient who will conduct the radical prostatectomy at 24 week."},{"outcome_type":"secondary","measure":"The mean PSA by the end of NHT","time_frame":"From baseline to 24 week","description":"which will be derived using the value of mean PSA by the end of NHT"},{"outcome_type":"secondary","measure":"Percentage of positive surgical margin for primary tumour","time_frame":"From baseline to 24 week","description":"Which will be derived using the number of positive surgical margin at 24 week"},{"outcome_type":"secondary","measure":"Incidence of seminal vesicle invasion","time_frame":"From baseline to 24 week.","description":"Which will be derived using the value of incidence of seminal vesicle invasion at 24 week"},{"outcome_type":"secondary","measure":"Percentage of pathological downstaging","time_frame":"From baseline to 24 week","description":"Which will be derived using the number of pathological downstaging at 24 week."},{"outcome_type":"secondary","measure":"surgical-related variables at 12 weeks, potent rates in erectile function at 12 weeks after surgery","time_frame":"From 24 week to 36 week","description":"Which will be derived using the value of observe surgical-related variables and complications at week 36"},{"outcome_type":"secondary","measure":"PFS","time_frame":"From baseline to the end of study","description":"Which will be derived using the number of PFS at the end of study"},{"outcome_type":"secondary","measure":"AEs/SAEs","time_frame":"From baseline to 28 week","description":"To evaluate the safety of NHT using goserelin and bicalutamide"},{"outcome_type":"secondary","measure":"PSA change from baseline","time_frame":"From baseline to 24 week","description":"Which will be derived using the value of PSA at the baseline."},{"outcome_type":"secondary","measure":"Involvement of bilateral pelvic lymph nodes","time_frame":"From baseline to 24 week","description":"Which will be derived using the value of involvement of bilateral pelvic lymph nodes at 24 week."},{"outcome_type":"secondary","measure":"OS","time_frame":"From baseline to the end of study","description":"Which will be derived using the number of OS at the end of study."}]}
{"nct_id":"NCT04711252","start_date":"2021-01-28","phase":"Phase 3","enrollment":1342,"brief_title":"A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease.","official_title":"SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease","primary_completion_date":"2025-11-10","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2029-02-12","last_update":"2021-09-22","description":"The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.","other_id":"D8532C00001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":130,"population":"","criteria":"\n        Inclusion criteria:\r\n\r\n          -  Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with\r\n             concomitant, approved LHRH agonists for the duration of the study treatment.\r\n\r\n          -  De novo Stage 4 disease, or recurrence from early stage disease after standard\r\n             adjuvant endocrine therapy meeting either one of the following criteria:\r\n\r\n               1. Received at least 24 months of AI treatment as part of their adjuvant therapy and\r\n                  at least 12 months have elapsed since the patient's last dose of adjuvant AI\r\n                  therapy without disease progression on treatment\r\n\r\n               2. Received at least 24 months of tamoxifen treatment as part of their adjuvant\r\n                  endocrine therapy\r\n\r\n          -  Histologically or cytologically documented diagnosis of ER+, HER2-negative breast\r\n             cancer based on local laboratory results.\r\n\r\n          -  Previously untreated with any systemic anti-cancer therapy for their locoregionally\r\n             recurrent or metastatic ER+ disease.\r\n\r\n          -  Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic +\r\n             sclerotic) bone lesion that can be assessed by CT or MRI.\r\n\r\n          -  Eastern Cooperative Oncology Group performance status of 0 or 1.\r\n\r\n          -  Adequate organ and marrow function.\r\n\r\n          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory\r\n             tests, and other study procedures.\r\n\r\n        Exclusion criteria:\r\n\r\n          -  Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor\r\n             with disease recurrence while on or within 12 months of completing treatment.\r\n\r\n          -  Previous treatment with AZD9833.\r\n\r\n          -  Participation in another clinical study with a study treatment or investigational\r\n             medicinal device administered in the last 4 weeks prior to randomization or concurrent\r\n             enrollment in another clinical study, unless it is an observational\r\n             (non-interventional) clinical study or during the follow-up period of an\r\n             interventional study.\r\n\r\n          -  Advanced, symptomatic, visceral spread, that are at risk of life-threatening\r\n             complications in the short term.\r\n\r\n          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or\r\n             leptomeningeal disease.\r\n\r\n          -  Any clinically important and symptomatic heart disease .\r\n\r\n          -  Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.\r\n\r\n          -  As judged by the investigator, any evidence of diseases (such as severe or\r\n             uncontrolled systemic diseases, renal transplant and active bleeding diseases) which,\r\n             in the investigator's opinion, makes it undesirable for the participant to participate\r\n             in the study or that would jeopardize compliance with the protocol.\r\n\r\n          -  Any concurrent anti-cancer treatment.\r\n\r\n        The above information is not intended to contain all considerations relevant to a patient's\r\n        potential participation in a clinical trial.\r\n      ","sponsor":"AstraZeneca","sponsor_type":"Industry","conditions":"ER-Positive HER2-Negative Breast Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AZD9833","description":"Dosage formulation: AZD9833 tablets will be administered orally"},{"intervention_type":"Drug","name":"Drug: Anastrozole","description":"Dosage formulation: Anastrozole tablets will be administered orally."},{"intervention_type":"Drug","name":"Drug: Anastrozole placebo","description":"Dosage formulation: anastrozole placebo tablets will be administrated orally."},{"intervention_type":"Drug","name":"Drug: AZD9833 placebo","description":"Dosage formulation: AZD9833 placebo tablets will be administrated orally."},{"intervention_type":"Drug","name":"Drug: Palbociclib","description":"Dosage formulation: palbociclib tablets/capsules will be administered orally"},{"intervention_type":"Drug","name":"Drug: Luteinizing hormone-releasing hormone (LHRH) agonist","description":"Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist."}],"outcomes":[{"outcome_type":"primary","measure":"Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1","time_frame":"From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)","description":"PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From randomization until the date of death due to any cause (up to 8 years)","description":"The OS is defined as the time from randomization to death due to any cause."},{"outcome_type":"secondary","measure":"Second progression-free survival (PFS2)","time_frame":"From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)","description":"Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death."},{"outcome_type":"secondary","measure":"Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1","time_frame":"From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (up to 5 years)","description":"ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 1.1."},{"outcome_type":"secondary","measure":"Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1","time_frame":"From the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)","description":"The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression."},{"outcome_type":"secondary","measure":"Time to chemotherapy (TTC)","time_frame":"From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)","description":"Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause."},{"outcome_type":"secondary","measure":"Time to first subsequent anti-cancer therapy (TFST)","time_frame":"From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years)","description":"TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Clinical benefit rate at 24 weeks (CBR24)","time_frame":"At least 23 weeks after randomisation","description":"CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window)."},{"outcome_type":"secondary","measure":"Time to second subsequent therapy (TSST)","time_frame":"From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years)","description":"TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause."},{"outcome_type":"secondary","measure":"Plasma concentration of AZD9833 at specified timepoints","time_frame":"on Day 15","description":"To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration."},{"outcome_type":"secondary","measure":"Change from baseline in EORTC QLQ-C30 scale scores","time_frame":"From baseline to 24 weeks post progression (up to approximately 5 years)","description":"Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score."},{"outcome_type":"secondary","measure":"Change from baseline in EORTC QLQ-BR45 scale scores","time_frame":"From baseline to 24 weeks post progression (up to approximately 5 years)","description":"Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score."}]}
{"nct_id":"NCT04463771","start_date":"2021-01-26","phase":"Phase 2","enrollment":220,"brief_title":"Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy.","official_title":"An Umbrella Study of INCMGA00012 Alone and in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-Based Chemotherapy (POD1UM-204)","primary_completion_date":"2023-08-26","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-11-08","last_update":"2021-07-29","description":"This is a multicenter, open-label, nonrandomized, Phase 2 umbrella study of retifanlimab in participants who have advanced or metastatic endometrial cancer that has progressed on or after platinum-based chemotherapy. retifanlimab will be administered as monotherapy or in combination with other immunotherapy or targeted agents.","other_id":"INCMGA 0012-204","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Female","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Ability to comprehend and willingness to sign a written ICF for the study. Women 18\r\n             years of age or older (or as applicable per local country requirements).\r\n\r\n          -  Histologically confirmed diagnosis of advanced or metastatic endometrial cancer with\r\n             disease progression on or after treatment with at least 1 platinum-containing regimen\r\n             for advanced or metastatic disease.\r\n\r\n          -  Groups A and B: Have not been previously treated with a PD-(L)1 inhibitor.\r\n\r\n          -  Group A only: Tumor tissue tested as MSI-High\r\n\r\n          -  Group B only: Tumor tissue tested as deficient MMR or an ultra-mutated POLE tumor.\r\n\r\n          -  Group D only: Tumor tissue tested as having an FGFR 1,2,3 mutation or alteration\r\n             characterized as per protocol.\r\n\r\n          -  Must have at least 1 measurable tumor lesion per RECIST v1.1.\r\n\r\n          -  Willing to provide tumor tissue sample (fresh or archived).\r\n\r\n          -  ECOG performance status 0 to 1.\r\n\r\n          -  Willingness to avoid pregnancy.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Group A only: Histologically confirmed diagnosis of carcinosarcoma of the uterus.\r\n\r\n          -  Histologically confirmed diagnosis of sarcoma of the uterus.\r\n\r\n          -  Has disease eligible for potentially curative treatment.\r\n\r\n          -  Receipt of anticancer therapy within 28 days of the first administration of study\r\n             treatment, with the exception of localized radiotherapy.\r\n\r\n          -  Toxicity of prior therapy that has not recovered to  Grade 1 or baseline unless\r\n             approved by the medical monitor.\r\n\r\n          -  Groups C and D (combinations): limiting immune-related toxicity during prior\r\n             checkpoint inhibitor therapy.\r\n\r\n          -  Has an active autoimmune disease requiring systemic immunosuppression with\r\n             corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs\r\n             within 14 days before the first dose of study treatment.\r\n\r\n          -  Receiving chronic systemic steroids (> 10 mg/day of prednisone or equivalent):\r\n\r\n          -  Known active CNS metastases and/or carcinomatous meningitis.\r\n\r\n          -  Has known active hepatitis B or C.\r\n\r\n          -  Has received a live vaccine within 28 days of the planned start of study treatment.\r\n\r\n          -  Evidence of interstitial lung disease or active, noninfectious pneumonitis.\r\n\r\n          -  Participants who are known to be HIV-positive with some protocol exceptions.\r\n      ","sponsor":"Incyte Corporation","sponsor_type":"Industry","conditions":"Endometrial Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: retifanlimab","description":"INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles."},{"intervention_type":"Drug","name":"Drug: epacadostat","description":"epacadostat will be administered orally BID."},{"intervention_type":"Drug","name":"Drug: pemigatinib","description":"pemigatinib will be administered orally QD."}],"outcomes":[{"outcome_type":"primary","measure":"Group A - Objective Response Rate","time_frame":"up to 2.5 years","description":"Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee"},{"outcome_type":"secondary","measure":"Group A -Duration of Response","time_frame":"up to 2.5 years","description":"Defined as the time from the first documented objective response (CR or PR) according to RECIST v1.1 (as determined by ICR) until disease progression or death due to any cause."},{"outcome_type":"secondary","measure":"Group A - Disease Control Rate","time_frame":"up to 2.5 years","description":"Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response."},{"outcome_type":"secondary","measure":"Group A - Overall Survival","time_frame":"up to 3.5 years","description":"Defined as the time from the first dose of study treatment until death due to any cause."},{"outcome_type":"secondary","measure":"Groups B, C, and D - Objective Response Rate","time_frame":"up to 2 years","description":"Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee"},{"outcome_type":"secondary","measure":"Number of Treatment-Related Adverse Events","time_frame":"up to 4 years","description":"Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment."}]}
{"nct_id":"NCT04707248","start_date":"2021-01-25","phase":"Phase 1","enrollment":102,"brief_title":"A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors","official_title":"Phase I, Two-Part, Multi-Center, First-in-Human Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors","primary_completion_date":"2023-02-01","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-02-01","last_update":"2021-09-16","description":"This clinical trial will evaluate DS-6000a in participants with advanced renal cell carcinoma (RCC) and ovarian cancer (OVC). The main goals of this study will be to investigate the recommended dose of DS-6000a that can be given safely to participants, assess the side effects of DS-6000a, and evaluate the effectiveness of DS-6000a.","other_id":"DS6000-A-U101","allocation":"Non-Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Written informed consent\r\n\r\n          -  At least 18 years of age\r\n\r\n          -  Eastern Cooperative Oncology Group Performance Status score of 0 or 1\r\n\r\n          -  Availability of archived tumor tissue samples\r\n\r\n          -  Has a left ventricular ejection fraction (LVEF) 50% by either an echocardiogram\r\n             (ECHO) or multigated acquisition scan (MUGA) within 28 days before study start\r\n\r\n          -  Has adequate organ function within 7 days before the start of study treatment\r\n\r\n          -  Has an adequate treatment washout period prior to start of study treatment\r\n\r\n          -  Male participants with female partners of childbearing potential and female\r\n             participants of child-bearing potential must agree to use a highly effective form of\r\n             contraception or avoid intercourse during and upon completion of the study and for at\r\n             least 4 months (for males) and for at least 7 months (for females) after the last dose\r\n             of study drug.\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Has had prior treatment with other CDH6-targeted agents\r\n\r\n          -  Has had prior treatment with an ADC that consists of an exatecan derivative that is a\r\n             topoisomerase I inhibitor (e.g., trastuzumab deruxtecan, DS-1062a, DS-7300a)\r\n\r\n          -  Has history or current presence of CNS metastases except for participants who have\r\n             completed radiotherapy or surgery 2 weeks before the start of treatment and have no\r\n             evidence of disease progression in the CNS and no requirement for chronic\r\n             corticosteroid therapy within 2 weeks before the start of treatment\r\n\r\n          -  Has multiple primary malignancies, except adequately resected non-melanoma skin\r\n             cancer, curatively treated in situ disease, or other solid tumors curatively treated,\r\n             with no evidence of disease for 3 years)\r\n\r\n          -  Has a history of myocardial infarction or unstable angina within 6 months before study\r\n             treatment\r\n\r\n          -  Has a medical history of symptomatic congestive heart failure (New York Heart\r\n             Association classes II-IV) or a serious cardiac arrhythmia requiring treatment\r\n\r\n          -  Lung-specific intercurrent clinically significant illnesses\r\n\r\n          -  Has an uncontrolled infection requiring systemic therapy\r\n      ","sponsor":"Daiichi Sankyo, Inc.","sponsor_type":"Industry","conditions":"Renal Cell Carcinoma|Ovarian Tumor","interventions":[{"intervention_type":"Drug","name":"Drug: DS-6000a","description":"Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1"},{"intervention_type":"Drug","name":"Drug: DS-6000a","description":"Intravenous administration at RDE on Day 1 of Cycle 1"}],"outcomes":[{"outcome_type":"primary","measure":"Number of Participants With Dose-limiting toxicities (DLTs)","time_frame":"Day 1 to Day 21 in Cycle 1 (each cycle is 21 days)"},{"outcome_type":"primary","measure":"Number of Participants Reporting Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest","time_frame":"From start of treatment up to 30 days after last dose, up to approximately 24 months"},{"outcome_type":"secondary","measure":"Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for DS-6000a and its Metabolites","time_frame":"Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and every then 2 cycles: predose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for DS-6000a and its Metabolites","time_frame":"Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and every then 2 cycles: predose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Analysis Maximum Plasma Concentration (Cmax) for DS-6000a and its Metabolites","time_frame":"Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and then every 2 cycles: predose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) for DS-6000a and its Metabolites","time_frame":"Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and then every 2 cycles: predose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) for DS-6000a and its Metabolites","time_frame":"Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and then every 2 cycles: predose (each cycle is 21 days)"},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)","time_frame":"From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 24 months (each cycle is 21 days)","description":"ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR)."},{"outcome_type":"secondary","measure":"Duration of Response (DoR) Based on RECIST v1.1","time_frame":"From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 24 months","description":"DoR is defined as the duration from the first documented response to the date of progression or death due to any cause."},{"outcome_type":"secondary","measure":"Disease Control Rate (DCR) Based on RECIST v1.1","time_frame":"From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 24 months","description":"DCR is defined as the proportion of participants with BOR of CR, PR, or SD."},{"outcome_type":"secondary","measure":"Clinical Benefit Rate (CBR) Based on RECIST v1.1","time_frame":"From date of first documented response (CR, PR) whichever occurs first or SD lasting at least 180 days to disease progression or death (due to any cause), up to approximately 24 months","description":"CBR is defined as the proportion of participants with BOR of CR or PR, or participants with stable disease (SD) lasting at least 180 days."},{"outcome_type":"secondary","measure":"Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Percentage of Participants Who Have Treatment-emergent ADA","time_frame":"Cycle 1 Day 1, Cycle 1 Day 15, and pre-dose on Day 1 of Cycle 2 through Cycle 4; then every 2 cycles from Cycle 4 through the end of treatment visit (each cycle is 21 days), and 30-day safety follow up visit, up to approximately 24 months"}]}
{"nct_id":"NCT04643002","start_date":"2021-01-25","phase":"Phase 1/Phase 2","enrollment":117,"brief_title":"Isatuximab in Combination With Novel Agents in RRMM - Master Protocol","official_title":"Phase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol","primary_completion_date":"2026-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2026-01-31","last_update":"2021-06-02","description":"Primary Objectives: Part 1 (dose finding, experimental substudies): - To determine or confirm the recommended dose of novel agents when combined with isatuximab with or without dexamethasone in participants with RRMM. - Part 2 (expansion, experimental substudies): - To demonstrate the clinical benefit of novel agents combined with isatuximab with or without dexamethasone in terms of rate of very good partial response (VGPR) or better. Secondary Objectives: - To assess the overall response rate (ORR) in each treatment arm. - To assess the clinical benefit rate (CBR) in each treatment arm. - To assess the duration of response (DOR) in each treatment arm. - To assess the time to first response (TT1R) in each treatment arm. - To assess the time to best response (TTBR) in each treatment arm. - To assess safety and tolerability in each treatment arm. - To assess progression free survival (PFS) in each treatment arm. - To assess overall survival (OS) in each treatment arm. - To evaluate the potential immunogenicity of isatuximab and novel agents when applicable. - To characterize the PK of isatuximab and novel agents. - To assess disease and treatment related symptoms, cancer and disease specific health-related quality of life, global impact of side effects and confirm/establish clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores. -Substudy 1 (Control Arm): - To assess clinical outcomes assessments (COAs). - To assess the incidence of skeletal related events (SREs). - To assess the time to first occurrence of SRE. - To assess health care resource utilization related with SREs. -Substudy 2: - To assess pain intensity related to skeletal related events (SREs). - To assess the incidence of SREs. - To assess the time to first occurrence of SRE. - To assess health care resource utilization related with SREs. -Substudy 3: - To assess patient-reported visual functioning","other_id":"ACT16482","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion criteria :\r\n\r\n          -  Participant must be 18 years of age inclusive or older\r\n\r\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.\r\n\r\n          -  Participants with relapsed or refractory MM who have received at least 3 prior lines\r\n             of therapy for MM, including PIs and IMiDs or at least 2 prior lines if at least one\r\n             of these lines consisted of 2 or more multiagent regimens (eg, Induction regimen with\r\n             autologous stem cell transplant followed by maintenance).\r\n\r\n          -  RRMM with measurable disease:\r\n\r\n          -  Serum M protein 0.5 g/dL measured using serum protein immunoelectrophoresis and/or\r\n\r\n          -  Urine M protein 200 mg/24 hours measured using urine protein immunoelectrophoresis\r\n             and/or\r\n\r\n          -  Serum free light chain (sFLC) MM without measurable M protein in serum or urine per\r\n             previous criteria (serum Ig free light chain 10 mg/dL and abnormal serum Ig kappa\r\n             lambda free light chain ratio <0.26 or >1.65).\r\n\r\n          -  Men or woman or childbearing potential should agree to use contraception.\r\n\r\n          -  Substudy 01, 02, 03: Anti-CD38 therapy nave or prior exposure to such drugs without\r\n             being refractory but with a wash out of at least 6 months after the last dose.\r\n             \"Refractory\" is defined as progressing within 60 days of last dose of anti-CD38\r\n             targeting therapy.\r\n\r\n        Exclusion criteria:\r\n\r\n          -  Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal\r\n             gammopathy of undetermined significance, or smoldering myeloma.\r\n\r\n          -  Uncontrolled infection within 14 days prior to randomization.\r\n\r\n          -  Clinically significant cardiac (including valvular) or vascular disease within 3\r\n             months prior to randomization, eg, myocardial infarction, unstable angina, coronary\r\n             (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral\r\n             artery revascularization, left ventricular ejection fraction <40%, heart failure New\r\n             York Heart Association Classes III and IV, stroke, transient ischemic attack,\r\n             pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or\r\n             higher by NCI CTCAE Version 5.0).\r\n\r\n          -  Known acquired immunodeficiency syndrome-related illness or known human\r\n             immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis\r\n             A.\r\n\r\n          -  Uncontrolled or active hepatitis B virus (HBV) infection.\r\n\r\n          -  Active hepatitis C virus (HCV) infection.\r\n\r\n          -  Any of the following within 3 months prior to randomization: treatment resistant\r\n             peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory\r\n             bowel disease.\r\n\r\n          -  Second malignancy other than basal cell or squamous cell carcinoma of the skin or in\r\n             situ carcinoma, unless they are successfully treated with curative intent for more\r\n             than 3 years before randomization.\r\n\r\n          -  Any anti-MM drug treatment within 14 days before randomization, including\r\n             dexamethasone.\r\n\r\n          -  Participants with a contraindication to treatment.\r\n\r\n          -  Vaccination with a live vaccine 4 weeks before the start of the study.\r\n\r\n          -  Hemoglobin <8 g/dL.\r\n\r\n          -  Platelets <50  109/L.\r\n\r\n          -  Absolute neutrophil count <1.5  109/L.\r\n\r\n          -  Creatinine clearance <30 mL/min.\r\n\r\n          -  Total bilirubin >1.5  ULN, except for known Gilbert syndrome in which direct\r\n             bilirubin should be 2.5  ULN.\r\n\r\n          -  Aspartate aminotransferase and/or alanine aminotransferase >3  ULN.\r\n\r\n          -  Patients with grade 3 or 4 hypercalcemia\r\n\r\n        Substudy 01:\r\n\r\n        -Malabsorption syndrome or any condition that can significantly impact the absorption of\r\n        pomalidomide.\r\n\r\n        Substudy 02:\r\n\r\n          -  History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or\r\n             carcinoma in situ of the cervix, or other local tumors, even if considered cured by\r\n             local treatment.\r\n\r\n          -  Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the\r\n             first dose of SAR439459.\r\n\r\n          -  Prothrombin time or INR >1.5  upper limit of normal (ULN).\r\n\r\n        Substudy 03:\r\n\r\n          -  Current corneal epithelial disease except mild punctate keratopathy\r\n\r\n          -  Patients who have received prior therapy with belantamab mafodotin\r\n\r\n        The above information is not intended to contain all considerations relevant to a patient's\r\n        potential participation in a clinical trial.\r\n      ","sponsor":"Sanofi","sponsor_type":"Industry","conditions":"Plasma Cell Myeloma Refractory","interventions":[{"intervention_type":"Drug","name":"Drug: Isatuximab SAR650984","description":"Pharmaceutical form:Solution for injection Route of administration: intravenous"},{"intervention_type":"Drug","name":"Drug: Dexamethasone","description":"Pharmaceutical form:Tablet Route of administration: Oral"},{"intervention_type":"Drug","name":"Drug: Pomalidomide","description":"Pharmaceutical form:Capsule Route of administration: Oral"},{"intervention_type":"Drug","name":"Drug: SAR439459","description":"Pharmaceutical form:Solution for injection Route of administration: intravenous"},{"intervention_type":"Drug","name":"Drug: Belantamab mafodotin","description":"Pharmaceutical form:Solution for injection Route of administration: intravenous"}],"outcomes":[{"outcome_type":"primary","measure":"Part 1 (dose finding, experimental substudies): Determination of recommended dose of novel agents in combination with isatiximab","time_frame":"Through the end of cycle 1 (approximately 6 weeks)","description":"Determination or confirmation of the dose will be based on: safety and tolerability in terms of treatment emergent adverse events and serious adverse events (TEAEs/SAEs), dose-limiting toxicity occurrence, and laboratory parameters available information on pharmacokinetic (PK) (if appropriate) and biomarkers. Determination of the dose will be based on: safety and tolerability in terms of treatment-emergent adverse events/serious adverse events (SAEs), dose limiting toxicity occurrence, laboratory parameters, including pharmacokinetic and pharmacodynamic information vital signs, and findings from physical examination."},{"outcome_type":"primary","measure":"VGPR Rate (Rate of Very Good Partial Response Rate or Better) in experimental substudies","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"Part 2: (Arm B) VGPR or better rate is defined as the percentage of participants with a VGPR or better as defined by the 2016 International Myeloma Working Group (IMWG) response criteria, assessed by Investigator based on central laboratory values."},{"outcome_type":"secondary","measure":"Overall Response Rate (ORR) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"ORR, defined as the proportion of participants with stringent complete response (sCR), complete response (CR), VGPR, and partial response (PR), according to the 2016 IMWG criteria assessed by Investigator based on central laboratory values."},{"outcome_type":"secondary","measure":"To assess the clinical benefit rate (CBR) in each treatment arm.","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"CBR, defined as the proportion of participants with sCR, CR, VGPR, PR, or minimal response, according to the 2016 IMWG criteria assessed by Investigator based on central laboratory values."},{"outcome_type":"secondary","measure":"Duration of Response (DOR) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"DOR, defined as the time from the date of the first response that is subsequently confirmed for patients achieving PR or better to the date of first documented progressive disease (PD) or death, whichever happens first."},{"outcome_type":"secondary","measure":"Time to First Response (TT1R) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"TT1R, defined as the time from the date of randomization to the date of first response (PR or better) that is subsequently confirmed."},{"outcome_type":"secondary","measure":"Time to Best Response (TTBR) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"TTBR, defined as the time from the date of randomization to the date of first occurrence of best overall response (PR or better) that is subsequently confirmed."},{"outcome_type":"secondary","measure":"Safety and Tolerability in each treatment arm","time_frame":"Baseline to 30 days after last study treatment administration (up to approximately 28 months after first study treatment)","description":"Safety and tolerability assessed in terms of adverse events/SAEs, including second primary malignancies, laboratory parameters, vital signs, and findings from physical examination."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"PFS is defined as the time from the date of randomization to disease progression based on the Investigator assessment according to 2016 IMWG criteria or death from any cause, whichever happens first."},{"outcome_type":"secondary","measure":"Overall Survival (OS) in each treatment arm","time_frame":"Up to approximately 28 months after the First patient in or scheduled assessment","description":"OS is defined as the time from the date of randomization to death from any cause."},{"outcome_type":"secondary","measure":"Immunogenicity of isatuximab and novel agents","time_frame":"Cycle 1 day 1, Day 2 (only substudy 03), Day8, Day15, day 22/29; from Cycle2 to Cycle4 day 1 and day 15 and from Cycle5 and after day 1 only. The cycle is 28 days.","description":"Incidence of anti-drug antibodies (ADAs) for novel agents (experimental arms) and isatuximab."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) Parameters for Novel agents and isatuximab","time_frame":"Cycle 1 day 1, Day 2 (only substudy 03), Day8, Day15, day 22/29; from Cycle2 to Cycle4 day 1 and day 15 and from Cycle5 and after day 1 only. The cycle is 28 days.","description":"Concentration of novel agents (experimental arms) and isatuximab"},{"outcome_type":"secondary","measure":"Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"The EORTC core quality of life questionnaire (QLQ-C30) will be used to assess cancer-specific health-related quality of life (HRQL), disease and treatment-related symptoms and impact of symptoms."},{"outcome_type":"secondary","measure":"Disease- and treatment-related quality of life will be assessed using the EORTC multiple myeloma module (QLQ-MY20) questionnaire","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"The EORTC quality of life questionnaire will be used to measure myelomaspecific HRQL, disease and treatment -related symptoms and impact of symptoms."},{"outcome_type":"secondary","measure":"Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"A single item from the FACT-G GP5 will be used to assess the global impact of side effects."},{"outcome_type":"secondary","measure":"The intensity of skeletal-related events (SRE)-related bone pain will be assessed using the skeletal-related bone pain numeric rating scale (SRE-BP-NRS)","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"he SRE-BP-NRS) will be used to assess the intensity of SRE-related bone pain (on average and at its worst) for control arm only"},{"outcome_type":"secondary","measure":"Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Severity (PGIS)","time_frame":"n Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"Patient Global Impression of Severity (PGIS) scale will be utilized as anchors to estimate/confirmestablished clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores."},{"outcome_type":"secondary","measure":"Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Change (PGIC) scales","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"Patient Global Impression of Change (PGIC) scale will be utilized as anchors to estimate/confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores."},{"outcome_type":"secondary","measure":"SRE Incidence for control and experimental arms","time_frame":"Continuous throughout study assessment (up to approximately 28 months)","description":"SRE incidence, defined as the proportion of participants who experienced pathological fracture, radiation to bone, spinal cord compression, or surgery to bone as a first bone event."},{"outcome_type":"secondary","measure":"Time to First Occurrence of SRE Assessment","time_frame":"Continuous throughout study assessment (up to approximately 28 months)","description":"Time to first occurrence of SRE is defined as time from the date of randomization to the occurrence of first SRE."},{"outcome_type":"secondary","measure":"Assessment of Health care resource utilization related with SREs","time_frame":"On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.","description":"The Health Care Resource Use-SREs questionnaire (HCRU-SREs) will be used to assess the use of health care resources associated with these events."},{"outcome_type":"secondary","measure":"To assess patient-reported visual functioning-for experimental arm only","time_frame":"On Day1 Cycle 1, End of treatment and at first follow-up visit. The cycle is 28 days.","description":"An NEI VFQ-25 will be used to assess patient-reported visual functioning"}]}
{"nct_id":"NCT04911907","start_date":"2021-01-22","phase":"Phase 2","enrollment":120,"brief_title":"Clinical Study of Utidelone Injection in Patients With Advanced or Metastatic Solid Tumors","official_title":"Open, Two-stage, Multicenter, Monotherapy, Phase II Clinical Study of Utidelone Injection in Patients With Advanced or Metastatic Solid Tumors After Failure or Intolerability to Standard Treatment","primary_completion_date":"2022-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-06-30","last_update":"2021-09-01","description":"This trial is an open, two-stage, multi-center, phase II clinical trial to evaluate the efficacy and safety of Utidelone in advanced solid tumors (excluding breast cancer, lung cancer, and colorectal cancer) that have failed standard of treatment or were unable to perform standard treatment. This trial is divided into 2 stages, screening stage and expansion stage. In the screening stage, 10 patients were enrolled for each tumor type(including Squamous cell carcinoma of head and neck, Esophageal cancer, Stomach cancer, Pancreatic cancer, Cholangiocarcinoma, Ovarian cancer and Other solid tumors). Based on the results of the tumor type screening stage, the sponsor and the main investigator will have a discussion and have the alignment of tumor types to enter the expansion stage. The expansion stage will refine the inclusion / exclusion criteria and may adjust the treatment plan based on the tumor type and the combination drug selection. A total of 30-50 patients (including patients enrolled in the screening stage) were enrolled in each specified tumor type during the expansion stage.","other_id":"BG01-2002","allocation":"Non-Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":75,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Histologically or cytologically documented locally-advanced and/or metastatic solid\r\n             malignancy (including Squamous cell carcinoma of head and neck, Esophageal cancer,\r\n             Stomach cancer, Pancreatic cancer, Cholangiocarcinoma, Ovarian cancer and Other solid\r\n             tumors) that is incurable, and has failed prior standard therapy or for which standard\r\n             therapy is not appropriate.\r\n\r\n          2. Have measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST\r\n             1.1)\r\n\r\n          3. Age 18 -70 years old\r\n\r\n          4. ECOG performance status of 0-1\r\n\r\n          5. Life expectancy 3 months\r\n\r\n          6. Basically normal results from routine blood test within 1 week prior to enrollment\r\n\r\n               1. Absolute neutrophil count (ANC) >= 1.5 x 10^9/L\r\n\r\n               2. Hemoglobin >= 9 g/dL\r\n\r\n               3. Platelets >= 80 x 10^9/L\r\n\r\n          7. Basically normal liver and renal functions within 1 week prior to enrollment\r\n\r\n               1. total bilirubin =< 1.5 x ULN with direct bilirubin within normal range\r\n\r\n               2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN\r\n                  (ALT and AST =< 5 x ULN is acceptable if liver metastases are present)\r\n\r\n               3. Creatinine clearance>=50 ml/min\r\n\r\n          8. Women and men of childbearing potential must agree to take effective contraceptive\r\n             measures during the study and within six months after the last treatment. Female\r\n             patients must have negative urinary pregnancy test within 7 days before the first\r\n             treatment (postmenopausal women must have no menstruation for at least 12 months\r\n             before they are considered unable to conceive)\r\n\r\n          9. Patients who give written informed consent with good compliance.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Received chemotherapy, radiotherapy, biological therapy, endocrine therapy,\r\n             immunotherapy and other anti-tumor treatments within 4 weeks prior to enrollment while\r\n             participating in this trial, except for the following items:\r\n\r\n               1. Nitrosourea or mitomycin C is within 6 weeks before the first dosage of the study\r\n                  drug;\r\n\r\n               2. Oral fluorouracil and small molecule targeted drugs are 2 weeks before the first\r\n                  use of the study drug or 5 half-life periods of the drug (whichever is longer);\r\n\r\n               3. The traditional Chinese medicine with anti-tumor indication is within 2 weeks\r\n                  before the first use of the research medicine.\r\n\r\n          2. Received other unlaunched clinical research drugs or treatment within 4 weeks before\r\n             the first dosage of the research drug.\r\n\r\n          3. Have undergone major organ surgery (excluding needle biopsy) or experienced\r\n             significant trauma within 4 weeks prior to the first dosage of study drug, or require\r\n             elective surgery during the trial period.\r\n\r\n          4. Symptomatic peripheral neuropathy CTCAE 5.0 grade evaluation  grade 2\r\n\r\n          5. With severe allergies to castor oil, or have had serious adverse reactions with\r\n             anti-microtubule drugs in the past\r\n\r\n          6. Patients of pregnancy or breast feeding\r\n\r\n          7. Patients with AEs caused by any previous treatment (including systemic and local\r\n             treatment) that have not yet restored to GRADE 1 (excluding hair loss)\r\n\r\n          8. Patient with known active central nervous system (CNS) metastases and/or carcinomatous\r\n             meningitis.\r\n\r\n          9. Patients with active infections and currently need systemic anti-infective treatment\r\n\r\n         10. Patient with immunodeficiency, including a positive HIV antibody test.\r\n\r\n         11. Patients with history of active hepatitis B (hepatitis B virus titer> ULN), allow\r\n             prophylactic antiviral treatment other than interferon; have a history of hepatitis C\r\n             virus infection (hepatitis C antibody positive).\r\n\r\n         12. Patients with history of serious cardiovascular and cerebrovascular diseases.\r\n\r\n         13. Patients with mental disorders or patients with poor compliance.\r\n\r\n         14. Patients not fitted for this study determined by the investigators.\r\n      ","sponsor":"Beijing Biostar Technologies, Ltd","sponsor_type":"Industry","conditions":"Solid Tumor","interventions":[{"intervention_type":"Drug","name":"Drug: utidelone injection","description":"Utidelone monotherapy 35 mg/m2/day IV transfusing over 90 min. on day 1-day 5 of each 21 day cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Tumor response to utidelone treatment","time_frame":"12 months from first study treatment","description":"Reflected by percentage of tumor size reduction or regression, assessed by imaging techniques and expressed as Objective Response Rate (ORR) ORR is defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) according to RECIST. 1.1."},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR)","time_frame":"12 months from first study treatment"},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"18 months from first study treatment","description":"PFS is defined as the duration of time from first study treatment to disease progression or death from any cause as documented by the investigator"},{"outcome_type":"secondary","measure":"Safety profile associated with utidelone injection","time_frame":"18 months from first study treatment","description":"Observe and record incidence of Treatment-Emergent Adverse Events and severe adverse effects associated with utidelone injection"}]}
{"nct_id":"NCT04594811","start_date":"2021-01-21","phase":"Phase 2","enrollment":145,"brief_title":"NT-I7 in Combination With Nivolumab in Advanced Gastric, Gastro-Esophageal Junction or Esophageal Adenocarcinoma","official_title":"A Multicenter, Open-label, Randomized, Phase 2 Study of NT-I7 in Combination With Nivolumab Versus Nivolumab Monotherapy in Subjects With Advanced or Metastatic Gastric or Gastro-Esophageal Junction or Esophageal Adenocarcinoma Who Progressed on or Intolerant to 2 or More Prior Lines of Systemic Therapy","primary_completion_date":"2023-08-29","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-18","last_update":"2021-07-19","description":"The main purposes of the dose escalation part of this study is to determine the following in participants with gastric or gastro-esophageal junction (GEJ) or esophageal adenocarcinoma (EAC): - Safety and tolerability of NT-I7 in combination with nivolumab - Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) The main purposes of Phase 2 of this study is to make a preliminary assessment of the antitumor activity and long-term survival of NT-I7 in combination with nivolumab in participants with gastric or GEJ or EAC.","other_id":"NIT-109","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Have histologically or cytologically confirmed locally locally advanced or metastatic\r\n             carcinoma of Gastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma\r\n             (EAC) who progressed on or intolerant to 2 or more prior lines of chemotherapy and/or\r\n             targeted therapy in the advanced/metastatic setting. Participants with\r\n             HER2-overexpresing tumor who progressed on trastuzumab-based therapy and at least 1\r\n             other line of therapy are also eligible.\r\n\r\n             Note: GEJ adenocarcinomas are defined as tumors that have their center within 5 cm\r\n             proximal and distal of the anatomical cardia, as described in the Siewert\r\n             classification system (Siewert et al, 2000)\r\n\r\n          2. Have at least one measurable lesion according to RECIST 1.1.\r\n\r\n          3. Participants enrolling in the dose escalation phase must have biopsiable disease.\r\n             Participants must agree to provide a) pre- treatment tumor tissue sample and b)\r\n             on-treatment tumor biopsy.\r\n\r\n          4. Participants enrolled in the Phase 2 must agree to provide tumor tissue sample prior\r\n             to the start of treatment.\r\n\r\n          5. PD-L1 expression status must be determined by the study-designated central lab prior\r\n             to randomization (CPS <5 versus CPS  5) for participants enrolled in Phase 2.\r\n\r\n          6. Female participants are either postmenopausal for at least 1 year, are surgically\r\n             sterile for at least 6 weeks; if a female participant is of childbearing potential,\r\n             she must agree to remain abstinent (refrain from heterosexual intercourse) or to\r\n             follow instructions for one highly effective method of contraception for the duration\r\n             of study treatment and for 5 months after the last dose of study treatment.\r\n\r\n          7. Non-sterile male participants who are sexually active with female partners of\r\n             childbearing potential must agree to remain abstinent (refrain from heterosexual\r\n             intercourse) or to follow instructions for one highly effective method of\r\n             contraception for the duration of study treatment and for 3 months after the last dose\r\n             of study treatment.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Pregnant, or breastfeeding or expecting to conceive or father children within the\r\n             study duration from screening through 5 months (for female participants) or 3 months\r\n             (for male participants) after the last dose of study treatment.\r\n\r\n          2. Receiving any investigational therapy or any approved therapy for investigational use\r\n             within 4 weeks or 5 half-lives, whichever is longer, prior to first dose of study\r\n             treatment.\r\n\r\n          3. Has previously received checkpoint inhibitor (CPI) treatment for gastric cancer or GEJ\r\n             or EAC.\r\n\r\n          4. Has received prior radiotherapy within 2 weeks of start of study treatment.\r\n\r\n          5. Has received treatment with complementary medications (excluding, herbal supplements,\r\n             or traditional Chinese medications) to treat the disease under study within 2 weeks\r\n             prior to the first dose of study treatment.\r\n\r\n          6. Subjects are eligible if CNS metastases are asymptomatic and do not require immediate\r\n             treatment or have been treated and subjects have neurologically returned to baseline\r\n             (except for residual signs or symptoms related to the CNS treatment).\r\n\r\n          7. History of severe hypersensitivity reactions to monoclonal antibodies (mAbs) or\r\n             intravenous immunoglobulin preparation.\r\n\r\n          8. Clinically significant cardiac disease.\r\n\r\n          9. Has a history of allergy or intolerance (unacceptable adverse events [AEs]) to study\r\n             drug components or polysorbate-80-containing infusions.\r\n\r\n             Note: Polysorbate 80 is a buffer used to make NT-I7.\r\n\r\n         10. Has received a live vaccine within 4 weeks prior to the first dose of study drug.\r\n             Seasonal influenza vaccines for injection are generally killed virus vaccines and are\r\n             allowed.\r\n\r\n         11. Has had an allogenic tissue/solid organ transplant or bone marrow transplant.\r\n      ","sponsor":"NeoImmuneTech","sponsor_type":"Industry","conditions":"Gastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC)","interventions":[{"intervention_type":"Drug","name":"Drug: NT-17","description":"Administered by intramuscular (IM) injection."},{"intervention_type":"Drug","name":"Drug: Nivolumab","description":"Administered by intravenous (IV) injection."}],"outcomes":[{"outcome_type":"primary","measure":"Dose escalation: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)","time_frame":"Up to 1 year"},{"outcome_type":"primary","measure":"Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 adverse events","time_frame":"Up to 1 year"},{"outcome_type":"primary","measure":"Dose escalation: Number of participants who experience one or more dose limiting toxicities (DLTs)","time_frame":"Up to 1 year"},{"outcome_type":"primary","measure":"Dose escalation: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade ≥ 3 dose limiting toxicities (DLTs)","time_frame":"Up to 1 year"},{"outcome_type":"primary","measure":"Phase 2: Objective response rate (ORR)","time_frame":"Up to 2 years","description":"ORR is defined as the percentage of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR), per RECIST 1.1."},{"outcome_type":"primary","measure":"Phase 2: Overall survival (OS)","time_frame":"Up to 2 years","description":"OS is defined as the time from first study treatment to death from any cause."},{"outcome_type":"secondary","measure":"Duration of response (DoR)","time_frame":"Up to 3 years","description":"DOR is defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, per RECIST 1.1."},{"outcome_type":"secondary","measure":"Disease control rate (DCR)","time_frame":"Up to 3 years","description":"DCR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), per RECIST 1.1."},{"outcome_type":"secondary","measure":"Progression free survival (PFS)","time_frame":"Up to 3 years","description":"PFS is defined as the time from the first study treatment to the first occurrence of disease progression or death of any cause, whichever occurs first, per RECIST 1.1."},{"outcome_type":"secondary","measure":"Number of participants with anti-drug antibodies (ADA) to NT-17","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"PFS Rate","time_frame":"Baseline to month 6"},{"outcome_type":"secondary","measure":"PFS Rate","time_frame":"Baseline to month 9"}]}
{"nct_id":"NCT04415853","start_date":"2021-01-21","phase":"Phase 3","enrollment":416,"brief_title":"Study of Larotinib in Unresectable Advanced or Recurrent Esophageal Cancer","official_title":"Lerotinib Versus Investigator's Choice Single-agent Chemotherapy in Patients With Locally Advanced/Metastatic Esophageal Squamous Cell Carcinoma and EGFR Overexpression That Progressed After Second-line Therapy:Phase 3 Study","primary_completion_date":"2022-08-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2022-11-30","last_update":"2021-07-08","description":"This is a randomized, controlled, multi-center, open trial, unresectable locally advanced or metastatic esophageal squamous cell carcinoma patients that failed at least second-line treatment and overexpressed EGFR were enrolled and randomly assigned to the experimental group and control group at a 1: 1 ratio.,who received Larotinib and the chemotherapy regimen chosen by the investigator (Irinotecan Hydrochloride Injection or Tegafur Gimeracil Oteracil Potassium Capsule),respecitively. Subjects are administered until disease progression assessed by the RECIST V1.1 standard (unless the investigator evaluates that the subject continues to have clinical benefit from continuing treatment, the subject may be allowed to continue treatment), and begins to receive new anti-tumor treatment, unacceptable toxicity, withdrawal of informed consent, or other conditions that meet the criteria for terminating trial treatment / withdrawal from the trial. The research phase of this study is divided into pre-screening period (~ D-28), screening period (D-28 ~ D-1), treatment period, treatment end visit ( 7 days after the last dose), safety follow-up ( Until 28  7 days after the last dose) and survival follow-up.","other_id":"PCD-DZ650-20-001","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"maximum_age":80,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Age:18-75 years, male or female.\r\n\r\n          2. Histologically or cytologically confirmed squamous cell carcinoma of the esophagus or\r\n             advanced/metastatic disease.\r\n\r\n          3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\r\n\r\n          4. Life expectancy of greater than 3 months.\r\n\r\n          5. Documented objective radiographic or clinical disease progression on two previous\r\n             lines of standard therapy.\r\n\r\n          6. Can provide archival tumor tissue sample for biomarker analysis (such as EGFR\r\n             overexpression/expansion status), biopsies are required if tissue samples cannot be\r\n             provided\r\n\r\n          7. Confirmed by the central laboratory as EGFR high expression.\r\n\r\n          8. Evaluable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.\r\n\r\n          9. Ability to swallow drugs.\r\n\r\n         10. Adequate organ function.\r\n\r\n         11. Voluntarily join the study and sign informed consent ad has good compliance.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Prior therapies with EGFR targeted drugs including EGFR antibodies.\r\n\r\n          2. Previously treated with Irinotecan and Tegafur.\r\n\r\n          3. Anthracycline, nitrosourea, and mitomycin within 6 weeks; traditional Chinese medicine\r\n             for anti-tumor within 2 weeks;immune anti-tumor therapy. within 8 weeks;other\r\n             anti-tumor therapies within 4 weeks before randomization.\r\n\r\n          4. Not recovered from adverse events due to a previously administered agent.\r\n\r\n          5. Have undergone major surgery within 4 weeks prior to randomization (not including\r\n             diagnostic surgery) or expect major surgery during the study period.\r\n\r\n          6. Previously or currently participating in other clinical trials within 4 weeks before\r\n             randomization (subjects who have entered the follow-up period are calculated based on\r\n             the last use of experimental drugs or devices).\r\n\r\n          7. Received a live vaccine within 28 days before randomization or plan to receive live\r\n             vaccine after enrollment.\r\n\r\n          8. Received a strong inducer or inhibitor of CYP3A4 enzyme within 1 week or received\r\n             Solivudine or its structurally similar drugs within 56 days prior to randomization.\r\n\r\n          9. Simultaneously receiving any other anti-tumor treatment.\r\n\r\n         10. Has a known additional malignancy previously within the last 5 years with the\r\n             exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or\r\n             any other tumor that has been cured\r\n\r\n         11. Central nervous system metastasis or uncontrolled central nervous system metastasis\r\n             currently in need of treatment; or confirmed central nervous system metastasis, but\r\n             not stable for more than 4 weeks after anti-tumor therapy; spinal cord compression,\r\n             cancerous meningitis, or meningitis.\r\n\r\n         12. Clinically obvious gastrointestinal abnormalities, which may affect the intake,\r\n             transport or absorption of drugs.\r\n\r\n         13. Having active gastrointestinal ulcer, active gastrointestinal bleeding, and\r\n             perforation;\r\n\r\n         14. Risk of major bleeding or esophageal fistula;\r\n\r\n         15. Previous or present with interstitial lung disease or immunotherapy-associated\r\n             pneumonia; currently suffering from drug-induced pneumonia, radiation pneumonitis\r\n             requiring steroid therapy, or clinically symptomatic active pneumonia, or other\r\n             moderate to severe lungs that seriously affect lung function disease\r\n\r\n         16. Active infection during the screening period (including but not limited to infection\r\n             requiring intravenous drip therapy), or unexplained fever (> 38.5C)within 2 weeks\r\n             prior to randomization.\r\n\r\n         17. Has congenital or acquired immune deficiency (such as HIV infection).\r\n\r\n         18. Known active Hepatitis B or C.\r\n\r\n         19. Has any of the following diseases within the first 12 months of randomization:\r\n             myocardial infarction, coronary artery bypass grafting or peripheral artery bypass\r\n             graft surgery, heart failure (NYHA III to IV), etc and unstable angina with 6 months.\r\n\r\n         20. Has thrombosis or embolism occurred within the first 12 months of randomization, such\r\n             as cerebrovascular accident (including transient ischemic attack), deep vein\r\n             thrombosis, pulmonary embolism with heparin or other similar drugs.\r\n\r\n         21. QTc interval (QTcF) corrected by Fridericia method> 470 ms; history of congenital long\r\n             QT interval syndrome; any history of clinically significant ventricular arrhythmias\r\n             (such as ventricular tachycardia, ventricular fibrillation) Or torsion-type\r\n             ventricular tachycardia); left ventricular ejection fraction (LVEF) <50%.\r\n\r\n         22. Allergies or contraindications to Z650 excipients (mannitol, sodium carboxymethyl\r\n             starch, micronized silica gel, magnesium stearate, silicified microcrystalline\r\n             cellulose), or to Irinotecan or Tegafur or its formulation ingredients.\r\n\r\n         23. Has uncontrolled pleural effusion, pericardial effusion, pelvic effusion, or ascites\r\n             requiring repeated drainage.\r\n\r\n         24. Has a history of organ transplantation or a history of allogeneic bone marrow\r\n             transplantation.\r\n\r\n         25. Pregnant, breastfeeding, or expecting to conceive or father children within the\r\n             projected duration of the study, starting with the screening visit through 6 months\r\n             after the last dose of study medication.\r\n\r\n         26. Has other serious acute or chronic diseases and are not suitable for participating in\r\n             clinical trials judged by investigators.\r\n      ","sponsor":"Sunshine Lake Pharma Co., Ltd.","sponsor_type":"Industry","conditions":"Esophageal Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Lerotinib","description":"Specification: 50 mg/capsule and 150 mg/capsule"},{"intervention_type":"Drug","name":"Drug: Irinotecan/Tegafur","description":"Irinotecan:Specification: 2mL: 40mg;5mL:0.1g Tegafur:20mg/capsule"}],"outcomes":[{"outcome_type":"primary","measure":"Overall survival","time_frame":"up to approximately 22 months","description":"Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data."},{"outcome_type":"secondary","measure":"Progression-free survival","time_frame":"up to approximately 22 months","description":"defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first."},{"outcome_type":"secondary","measure":"Objective response rate","time_frame":"up to approximately 22 months","description":"Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by investigators"},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"up to approximately 22 months","description":"Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response"},{"outcome_type":"secondary","measure":"Changes in health-related quality of life with esophageal cancer symptom scale","time_frame":"up to approximately 22 months","description":"To evaluate changes in health-related quality of life in patients with advanced esophageal cancer according to the Questionnaire"},{"outcome_type":"secondary","measure":"Incidence of Treatment-Emergent Adverse Events","time_frame":"up to approximately 22 months","description":"Assessed by Percentage of Participants With Adverse Events during the treatment assessed by NCI CTCAE 5.0"},{"outcome_type":"secondary","measure":"Apparent Oral Clearance (CL/F) of Lerotinib","time_frame":"up to approximately 22 months","description":"Defined as oral dose clearance"},{"outcome_type":"secondary","measure":"Apparent Volume of Distribution (Vd/F) of Lerotinib","time_frame":"up to approximately 22 months","description":"Apparent volume of distribution after administration."}]}
{"nct_id":"NCT04544189","start_date":"2021-01-20","phase":"Phase 2","enrollment":135,"brief_title":"Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer","official_title":"A Phase II Randomized Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Chinese Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, PIK3CA Mutant Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment, Including a Subset With Pharmacokinetic Analysis","primary_completion_date":"2023-11-13","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-07-30","last_update":"2021-08-11","description":"The primary objective is to evaluate whether treatment with alpelisib in combination with fulvestrant prolongs Progression Free Survival (PFS) compared to treatment with placebo in combination with fulvestrant. The primary scientific question of interest is: what is the treatment effect based on PFS for alpelisib in combination with fulvestrant versus placebo in combination with fulvestrant in Chinese men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation, who received prior treatment with an aromatase inhibitor (AI) either as (neo) adjuvant treatment or as treatment for advanced disease, regardless of study treatment discontinuation or start of new anti-neoplastic therapy.","other_id":"CBYL719C2201","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Quadruple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Key Inclusion Criteria:\r\n\r\n          -  Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by\r\n             a Novartis designated laboratory. One new or recent biopsy (collected at screening if\r\n             feasible) or archival tumor block or slides (3 slides minimum from a surgical\r\n             specimen, or 7 slides minimum from a core needle biopsy) must be provided. It is\r\n             recommended to provide a tumor sample collected after the most recent progression or\r\n             recurrence.\r\n\r\n          -  Chinese man or postmenopausal woman  18 years of age\r\n\r\n          -  Participant has identified PIK3CA mutation (as determined by a Novartis designated\r\n             laboratory)\r\n\r\n          -  Participant has a histologically and/or cytologically confirmed diagnosis of ER+\r\n             and/or PgR+ breast cancer by local laboratory.\r\n\r\n          -  Participant has HER2-negative breast cancer defined as a negative in situ\r\n             hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ\r\n             hybridization (FISH, CISH or SISH) test is required by local laboratory testing\r\n\r\n          -  Participant has either\r\n\r\n          -  Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a\r\n             lesion at a previously irradiated site may only be counted as a target lesion if there\r\n             is clear sign of progression since the irradiation) OR\r\n\r\n          -  If no measurable disease is present, then at least one predominantly lytic bone lesion\r\n             must be present (Participants with no measurable disease and only one predominantly\r\n             lytic bone lesion that has been previously irradiated are eligible if there is\r\n             documented evidence of disease progression of the bone lesion after irradiation).\r\n\r\n          -  Participant has advanced (loco regionally recurrent not amenable to curative therapy\r\n             or metastatic) breast cancer.\r\n\r\n          -  Participants may be:\r\n\r\n          -  relapsed with documented evidence of progression while on (neo) adjuvant endocrine\r\n             therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no\r\n             treatment for metastatic disease\r\n\r\n          -  relapsed with documented evidence of progression more than 12 months from completion\r\n             of (neo)adjuvant endocrine therapy and then subsequently progressed with documented\r\n             evidence of progression while on or after only one line of endocrine therapy for\r\n             metastatic disease\r\n\r\n          -  newly diagnosed advanced breast cancer, then relapsed with documented evidence of\r\n             progression while on or after only one line of endocrine therapy\r\n\r\n          -  Patient has ECOG performance status 0 or 1.\r\n\r\n          -  Patient has adequate bone marrow function.\r\n\r\n        Key Exclusion Criteria\r\n\r\n          -  Participant with symptomatic visceral disease or any disease burden that makes the\r\n             Participant ineligible for endocrine therapy per the investigator's best judgment.\r\n\r\n          -  Participant has received prior treatment with chemotherapy (except for (neo)adjuvant/\r\n             adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor.\r\n\r\n          -  Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the\r\n             excipients of alpelisib or fulvestrant.\r\n\r\n          -  Participant has received radiotherapy  4 weeks or limited field radiation for\r\n             palliation  2 weeks prior to randomization, and who has not recovered to grade 1 or\r\n             better from related side effects of such therapy (with the exception of alopecia)\r\n             and/or from whom  25% of the bone marrow was irradiated.\r\n\r\n          -  Participant has a concurrent malignancy or malignancy within 3 years of randomization,\r\n             with the exception of adequately treated, basal or squamous cell carcinoma,\r\n             non-melanomatous skin cancer or curatively resected cervical cancer.\r\n\r\n          -  Participant with an established diagnosis at screening of diabetes mellitus type I or\r\n             not controlled type II\r\n\r\n          -  Participant has currently documented pneumonitis/interstitial lung disease\r\n\r\n          -  History of acute pancreatitis within 1 year of screening or a past medical history of\r\n             chronic pancreatitis\r\n\r\n          -  Participant with unresolved osteonecrosis of the jaw\r\n\r\n          -  Participant has a history of severe cutaneous reactions like Stevens- Johnson-Syndrome\r\n             (SJS), Erythema Multiforme (EM), or Toxic Epidermal Necrolysis (TEN), or Drug Reaction\r\n             with Eosinophilia and Systemic Symptoms (DRESS).\r\n\r\n        Other protocol-defined inclusion/exclusion criteria may apply.\r\n      ","sponsor":"Novartis Pharmaceuticals","sponsor_type":"Industry","conditions":"Breast Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: Alpelisib","description":"300mg (oral) once daily, in a 28-day cycle"},{"intervention_type":"Drug","name":"Drug: Fulvestrant","description":"Fulvestrant 500 mg (intramuscular, as two 250mg/5 mL injections) on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter"},{"intervention_type":"Drug","name":"Drug: Placebo","description":"300 mg by mouth once daily, in a 28-day cycle"}],"outcomes":[{"outcome_type":"primary","measure":"Progression Free Survival (PFS)","time_frame":"From the date of randomization to the date of the first documented progression or death due to any cause, up to approximately 34 months","description":"PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. The primary analysis for PFS will be performed based on local radiology assessment according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From date of randomization to date of death due to any cause, up to approximately 48 months.","description":"OS is defined as the time from date of randomization to date of death due to any cause. OS will be analyzed in the FAS population according to the randomized treatment arm and strata assigned at randomization."},{"outcome_type":"secondary","measure":"Overall response rate (ORR)","time_frame":"Up to approximately 34 months","description":"Overall response rate (ORR) with confirmed response is defined as the proportion of subjects with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator's assessment according to RECIST 1.1"},{"outcome_type":"secondary","measure":"Clinical benefit rate (CBR) with confirmed response","time_frame":"Up to approximately 34 months","description":"CBR is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (PR) or an overall response of confirmed stable disease (SD), lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per local review according to RECIST 1.1."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK): Trough concentration of alpelisib in plasma","time_frame":"Predose at Cycle (C) 1 Day (D) 15, C2 D1, C4 D1 and C6 D1 (Cycle=28 days)","description":"Pre-dose concentration of alpelisib at steady state on planed days. Measurement of alpelisib will be performed only in subjects randomized to the alpelisib arm."},{"outcome_type":"secondary","measure":"Time to definitive deterioration in Eastern Cooperative Oncology Group (ECOG) performance status (PS)","time_frame":"Up to approximately 30 months.","description":"PS will be assessed using ECOG scale. The scale consists of 4 grades (from 0 to 4) where 0 implies fully active and 4 implies completely disabled. Subjects will be censored if no definitive deterioration in ECOG PS is observed before the analysis cut-off date. The censoring date will be the date of the last PS assessment prior to cut- off. (Approximately up to 30 months)"},{"outcome_type":"secondary","measure":"Number of participants with Adverse Events (AEs)","time_frame":"From date of randomization until the end of the study, up to approximately 48 months","description":"Incidence, type, and severity of AEs per CTCAE version 4.03 criteria including changes in laboratory values, vital signs, liver assessments and cardiac assessments"},{"outcome_type":"secondary","measure":"Number of participants with dose interruptions","time_frame":"Up to approximately 30 months","description":"Tolerability measured by the number of subjects who have interruptions of study treatment"},{"outcome_type":"secondary","measure":"Number of participants with dose reductions","time_frame":"Up to approximately 30 months","description":"Tolerability measured by the number of subjects who have reductions of study treatment."},{"outcome_type":"secondary","measure":"Dose intensity","time_frame":"Up to approximately 30 months","description":"Tolerability measured by the dose intensity of study drug"},{"outcome_type":"secondary","measure":"PFS based on local radiology assessments and using RECIST 1.1 criteria by PIK3CA mutation status measured in baseline ctDNA","time_frame":"Baseline and from randomization up to approximately 34 months","description":"PFS defined as the time from the date of randomization to the date of the first documented progression based on local radiology assessment and according to RECIST 1.1 or death due to any cause. Results will be presented by PIK3CA mutation status measured in baseline ctDNA"},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Maximum observed plasma concentration (Cmax)","time_frame":"Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1","description":"Blood samples are collected at indicated time-points for analysis of Cmax in PK cohort."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Time to reach maximum plasma concentration (Tmax)","time_frame":"Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1","description":"Blood samples are collected at indicated time-points for analysis of Tmax in PK cohort."},{"outcome_type":"secondary","measure":"Pharmacokinetics (PK) of alpelisib when given in combination with fulvestrant (PK cohort): Area under the curve from time 0 to 24h (AUC0-24h)","time_frame":"Cycle (C) 1 Day (D) 1 and 15 pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post-dose; and pre-dose on C2D1, C4D1 and C6D1","description":"Blood samples are collected at indicated time-points for analysis of AUC0-24h in PK cohort"}]}
{"nct_id":"NCT04687241","start_date":"2021-01-18","phase":"Phase 3","enrollment":192,"brief_title":"Almonertinib Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB Non-Small Cell Lung Cancer With EGFR-sensitive Mutations","official_title":"Efficacy and Safety of Almonertinib Versus Placebo as Adjuvant Therapy for Subjects With Resected Stage II-IIIB NSCLC Harboring EGFR-sensitive Mutations: A Randomized, Controlled, Double-blind, Phase 3 and Multicenter Clinical Study","primary_completion_date":"2026-01-18","study_type":"Interventional","rec_status":"Not yet recruiting","completion_date":"2029-01-01","last_update":"2020-12-29","description":"To assess the efficacy and safety of Almonertinib versus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm+) stage II-IIIB non-small cell lung cancer (NSCLC), following complete tumor resection with or without adjuvant chemotherapy.","other_id":"HS-10296-302","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"Triple","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  1. Provision of informed consent before any study-specific procedures, sampling and\r\n             analyses.\r\n\r\n             2. Male or female, age at least 18 years. 3. Histologically confirmed diagnosis of\r\n             primary non-small lung cancer (NSCLC) on predominantly non-squamous histology.\r\n\r\n             4. MRI or CT scan of the brain must be done before surgery to exclude brain\r\n             metastasis.\r\n\r\n             5. Complete surgical resection of the primary NSCLC and lymphadenectomy are mandatory.\r\n             All gross disease must have been removed at the end of surgery. All surgical margins\r\n             of resection must be negative for tumor.\r\n\r\n             6. Patients must be classified post-operatively as Stage IIA, IIB, IIIA or IIIB (only\r\n             T3N2M0) based on pathologic criteria.\r\n\r\n             7. Confirmation by the central laboratory that the tumor harbors one of the 2 common\r\n             EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R),\r\n             either alone or in combination with other EGFR mutations including T790M.\r\n\r\n             8. Complete recovery from surgery and standard post-operative therapy (if applicable)\r\n             at the time of randomization.\r\n\r\n             9. A WHO performance status of 0-1 with no deterioration over the past 2 weeks and a\r\n             minimum life expectancy of 12 weeks.\r\n\r\n             10. Female patients should be using adequate contraceptive measures and should not be\r\n             breastfeeding at the screening period, during the study, and six months after the last\r\n             dosing of study. A pregnancy test should be done before first dosing unless having\r\n             evidence of non-child-bearing potential.\r\n\r\n             11. Male patients should be willing to use barrier contraception (condoms).\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  1. Patients who have had only segmentectomies or wedge resections. 2. Treatment with\r\n             any of the following:\r\n\r\n               1. Any prior anticancer therapy for the current lung cancer (pre-operative\r\n                  (neoadjuvant) platinum-based or other chemotherapy, pre-operative or\r\n                  post-operative or planned radiation therapy, neoadjuvant or adjuvant EGFR-TKI,\r\n                  other targeted therapy and immunotherapy).\r\n\r\n               2. Major surgery (including primary tumor surgery, excluding placement of vascular\r\n                  access) within 3 weeks of the first dose of study drug.\r\n\r\n               3. Patients currently receiving medications or herbal supplements known to be strong\r\n                  inducers and inhibitors of cytochrome P450 (CYP) 3A4.\r\n\r\n               4. Treatment with an investigational drug within five half-lives of the compound or\r\n                  any of its related material.\r\n\r\n                  3. Inadequate bone marrow reserve or organ function. 4. Any of the following\r\n                  cardiac criteria:\r\n\r\n               1. Mean resting corrected QT interval (QTc) > 470 ms obtained from 3\r\n                  electrocardiograms (ECGs), using the screening clinic's ECG machine and\r\n                  Fridericia's formula for QT interval correction (QTcF).\r\n\r\n               2. Any clinically important abnormalities in rhythm, conduction, or morphology of\r\n                  the resting ECG (e.g., PR interval > 250 ms).\r\n\r\n               3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic\r\n                  events, such as heart failure or any concomitant medication known to prolong the\r\n                  QT interval.\r\n\r\n               4. Left ventricular ejection fraction (LVEF)  40%. 5. History of other\r\n                  malignancies, excluding full treated non-melanoma skin cancer, in-situ cancer, or\r\n                  other solid tumors that hadn't recurrent for > 5 years following the end of\r\n                  treatment.\r\n\r\n                  6. Any evidence of severe or uncontrolled systemic diseases (including\r\n                  uncontrolled hypertension and active bleeding diatheses) or active infection\r\n                  (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)).\r\n\r\n                  7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or\r\n                  inability to swallow the study drug that would preclude adequate absorption of\r\n                  Almonertinib.\r\n\r\n                  8. History of interstitial lung disease (ILD), drug-induced ILD, radiation\r\n                  pneumonitis which required steroid treatment, or any evidence of clinically\r\n                  active ILD.\r\n\r\n                  9. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 except\r\n                  alopecia and Grade 2 prior platinum-therapy related neuropathy.\r\n\r\n                  10. History of hypersensitivity to any active or inactive ingredient of\r\n                  Almonertinib or to drugs with a similar chemical structure or class to\r\n                  Almonertinib.\r\n\r\n                  11. Judgment by the investigator that the patient should not participate in the\r\n                  study if the patient is unlikely to comply study procedures, restrictions, and\r\n                  requirements.\r\n\r\n                  12. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's\r\n                  opinion, present a specific risk to the patient's safety.\r\n\r\n                  13. Any disease or condition that, in the opinion of the investigator, would\r\n                  compromise the safety of the patient or interfere with study assessments.\r\n      ","sponsor":"Jiangsu Hansoh Pharmaceutical Co., Ltd.","sponsor_type":"Industry","conditions":"Non-small Cell Lung Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: Almonertinib","description":"The initial dose of Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions."},{"intervention_type":"Drug","name":"Drug: Placebo Almonertinib","description":"Placebo Almonertinib"}],"outcomes":[{"outcome_type":"primary","measure":"DFS (Disease free survival) assessed by IRC (Independent Review Committee)","time_frame":"From the time of randomization to recurrence of tumor or death, approximately 4 years.","description":"DFS is defined as the time from randomization to the recurrence of tumor as assessed by IRC or death from any cause on study. The patients will receive long-term follow-up including chest and abdominal CT every 12 weeks during Year 1, then every 24 weeks during Years 2 to 5, and every 48 weeks during Year 6 and onwards; MRI/CT of brain, and bone scan performed every 48 weeks."},{"outcome_type":"secondary","measure":"DFS (Disease free survival) assessed by INVs (Investigators)","time_frame":"From the time of randomization to recurrence of tumor or death, approximately 4 years.","description":"The patients will receive long-term follow-up including chest and abdominal CT every 12 weeks during Year 1, then every 24 weeks during Years 2 to 5, and every 48 weeks during Year 6 and onwards; MRI/CT of brain, and bone scan performed every 48 weeks. DFS is defined as the time from randomization to the recurrence of tumor as assessed by INVs or death from any cause on study."},{"outcome_type":"secondary","measure":"DFS rate at 2, 3 and 5 years assessed by IRC","time_frame":"From the time of randomization to recurrence of tumor or death, approximately 6 years.","description":"Defined as the proportion of patients alive and disease free at 2, 3 and 5 years, respectively, estimated from Kaplan Meier plots of the primary endpoint of DFS at the time of the primary analysis."},{"outcome_type":"secondary","measure":"OS (Overall survival)","time_frame":"The time from randomization to death due to any cause, approximately 8 years.","description":"OS is defined as the time from randomization to death due to any cause. The survival will be followed up with telephone every 24 weeks after discontinuation of the randomized treatment."},{"outcome_type":"secondary","measure":"OS rate at 5 years","time_frame":"The time from randomization to death due to any cause, approximately 8 years.","description":"OS rate at 5 years is defined as the proportion of patients alive at 5 years."},{"outcome_type":"secondary","measure":"Incidence and severity of adverse events (AEs)","time_frame":"From the screening period to 28 days after treatment completion, approximately 4 years.","description":"AEs are graded according to CTCAE v5.0 and recorded in the case report form."},{"outcome_type":"secondary","measure":"Plasma concentrations of Almonertinib and HAS-719 metabolite.","time_frame":"From Cycle 3 (Each cycle =3 weeks) to Cycle 4, approximately 3 weeks.","description":"Defined as the pharmacokinetics exposure parameters derived from plasma concentrations of Almonertinib and its metabolite, HAS-719."}]}
{"nct_id":"NCT04665921","start_date":"2021-01-18","phase":"Phase 1","enrollment":225,"brief_title":"A Study of SGN-STNV in Advanced Solid Tumors","official_title":"A Phase 1 Study of SGN-STNV in Advanced Solid Tumors","primary_completion_date":"2022-12-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2023-12-31","last_update":"2021-09-21","description":"This trial will look at a drug called SGN-STNV to find out whether it is safe for patients with solid tumors. It will study SGN-STNV to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study how well SGN-STNV works to treat solid tumors. The study will have two parts. Part A of the study will find out how much SGN-STNV should be given to patients. Part B will use the dose found in Part A to find out how safe SGN-STNV is and if it works to treat certain types of solid tumors.","other_id":"SGNSTNV-001","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          -  Disease indication\r\n\r\n               -  Must have disease that is relapsed or refractory or be intolerant to\r\n                  standard-of-care therapies and should have no appropriate standard-of-care\r\n                  therapeutic option.\r\n\r\n                    -  Non-small cell lung cancer (NSCLC)\r\n\r\n                    -  HER2 negative breast cancer\r\n\r\n                    -  Ovarian cancer\r\n\r\n                    -  Cervical cancer\r\n\r\n                    -  Endometrial cancer\r\n\r\n                    -  Esophageal cancer\r\n\r\n                    -  Gastric cancer and GEJ carcinoma\r\n\r\n                    -  Colorectal cancer\r\n\r\n                    -  Exocrine pancreatic adenocarcinoma\r\n\r\n                    -  Appendiceal adenocarcinoma and pseudomyxoma peritonei of unknown origin\r\n\r\n          -  Participants enrolled in the following study parts should have a tumor site accessible\r\n             for biopsy and agree to biopsy as follows:\r\n\r\n               -  Disease-specific expansion cohorts, participant 13 onwards: pretreatment biopsy\r\n\r\n               -  Biology expansion cohort: pretreatment biopsy and additional on-treatment biopsy\r\n                  during Cycle 1\r\n\r\n          -  Measurable disease per the Response Evaluation Criteria in Solid Tumors Version 1.1\r\n             (RECIST v1.1) at baseline\r\n\r\n          -  An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\r\n\r\n          -  Adequate renal, hepatic, and hematologic function\r\n\r\n        Exclusion Criteria\r\n\r\n          -  History of another malignancy within 3 years before the first dose of study drug, or\r\n             any evidence of residual disease from a previously diagnosed malignancy.\r\n\r\n          -  Known active central nervous system metastases\r\n\r\n          -  Carcinomatous meningitis\r\n\r\n          -  Previous receipt of monomethylauristatin E (MMAE)-containing drugs\r\n\r\n          -  Pre-existing neuropathy  Grade 2 per the National Cancer Institute's Common\r\n             Terminology Criteria for Adverse Events (NCI CTCAE) v5.0\r\n\r\n          -  Any uncontrolled  Grade 3 (per the NCI CTCAE, Version 5.0) viral, bacterial, or\r\n             fungal infection within 2 weeks prior to the first dose of SGN-STNV\r\n\r\n        There are additional inclusion and exclusion criteria. The study center will determine if\r\n        criteria for participation are met.\r\n      ","sponsor":"Seagen Inc.","sponsor_type":"Industry","conditions":"Pseudomyxoma Peritonei|Appendiceal Adenocarcinoma|Exocrine Pancreatic Adenocarcinoma|Colorectal Neoplasms|Stomach Neoplasms|Gastroesophageal Junction Carcinoma|Esophageal Neoplasms|Endometrial Neoplasms|Uterine Cervical Neoplasms|Ovarian Neoplasms|HER2 Negative Breast Neoplasms|Carcinoma, Non-Small Cell Lung","interventions":[{"intervention_type":"Drug","name":"Drug: SGN-STNV","description":"Given into the vein (IV; intravenously)"}],"outcomes":[{"outcome_type":"primary","measure":"Incidence of adverse events (AEs)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"To be summarized using descriptive statistics"},{"outcome_type":"primary","measure":"Incidence of laboratory abnormalities","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"To be summarized using descriptive statistics"},{"outcome_type":"primary","measure":"Incidence of dose limiting toxicities","time_frame":"Up to 28 days","description":"To be summarized using descriptive statistics"},{"outcome_type":"secondary","measure":"Objective response rate (ORR) as assessed by the investigator per RECIST v1.1","time_frame":"Up to approximately 3 years","description":"ORR is defined as the proportion of subjects achieving a partial response (PR) or complete response (CR)."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS)","time_frame":"Up to approximately 3 years","description":"PFS is defined as the time from the start of any study treatment to first documentation of disease progression or to death due to any cause, whichever comes first."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to approximately 3 years","description":"OS is defined as the time from the start of any study treatment to the date of death due to any cause."},{"outcome_type":"secondary","measure":"Duration of objective response (DOR)","time_frame":"Up to approximately 3 years","description":"DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression or to death due to any cause, whichever comes first."},{"outcome_type":"secondary","measure":"Area under the concentration-time curve (AUC)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"Pharmacokinetic (PK) endpoint"},{"outcome_type":"secondary","measure":"Time to maximum concentration (Tmax)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"PK endpoint"},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"PK endpoint"},{"outcome_type":"secondary","measure":"Trough concentration (Ctrough)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"PK endpoint"},{"outcome_type":"secondary","measure":"Incidence of antidrug antibodies (ADA)","time_frame":"Through 30-37 days following last dose of SGN-STNV; up to approximately 3 years","description":"Immunogenicity endpoint"}]}
{"nct_id":"NCT04631601","start_date":"2021-01-15","phase":"Phase 1/Phase 2","enrollment":159,"brief_title":"Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)","official_title":"A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)","primary_completion_date":"2022-11-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-05-30","last_update":"2021-09-22","description":"This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).","other_id":"20190505","allocation":"Randomized","intervention_model":"Sequential Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"Male","minimum_age":18,"maximum_age":99,"population":"","criteria":"\n        All parts\r\n\r\n        Inclusion Criteria:\r\n\r\n          -   18 years of age (or legal adult age within country)\r\n\r\n          -  Subject has provided informed consent prior to initiation of any study-specific\r\n             activities/procedures\r\n\r\n          -  Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of\r\n             the prostate\r\n\r\n          -  Subjects should have undergone bilateral orchiectomy or should be on continuous\r\n             androgen deprivation therapy with a gonadotropin releasing hormone agonist or\r\n             antagonist (testosterone  50 ng/dL (or 1.7 nmol/L))\r\n\r\n        Exclusion Criteria:\r\n\r\n          -  Central nervous system (CNS) metastases or leptomeningeal disease\r\n\r\n          -  History or presence of clinically relevant CNS pathology\r\n\r\n          -  Confirmed history or current autoimmune disease or other diseases requiring permanent\r\n             immunosuppressive therapy\r\n\r\n          -  Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia\r\n             requiring medication, and/or symptomatic congestive heart failure (New York Heart\r\n             Association > class II) within 12 months\r\n\r\n          -  Prior treatment with a taxane for mCRPC\r\n\r\n          -  Major surgery and/or Radiation within 4 weeks\r\n\r\n          -  History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\r\n             infection unless agreed upon with medical monitor and meeting the following criteria:\r\n\r\n               -  Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR)\r\n                  within 72 hours of first dose of AMG 160 (or AMG 404 in Part 3)\r\n\r\n               -  No acute symptoms of COVID-19 disease within 10 days prior to first dose of AMG\r\n                  160 (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic\r\n                  subjects)\r\n\r\n        Prior/Concurrent Clinical Study Experience\r\n\r\n          -  Currently receiving treatment in another investigational device or drug study, or less\r\n             than 4 weeks since ending treatment on another investigational device or drug\r\n             study(ies). Other investigational procedures while participating in this study are\r\n             excluded with the exception of investigational scans.\r\n\r\n        Subprotocol A only:\r\n\r\n        Inclusion criteria\r\n\r\n         Subjects planning to receive enzalutamide for the first time for mCRPC\r\n\r\n        Exclusion criteria\r\n\r\n          -  Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers\r\n\r\n          -  Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19\r\n\r\n        Subprotocol B only:\r\n\r\n        Inclusion criteria\r\n\r\n          -  Subjects planning to receive abiraterone for the first time for mCRPC Exclusion\r\n             criteria\r\n\r\n          -  Baseline moderate and severe hepatic impairment (Child-Pugh Class B and C)\r\n\r\n          -  Presence of uncontrolled hypertension, hypokalemia, or fluid retention\r\n\r\n          -  History or presence of adrenocortical insufficiency\r\n\r\n          -  Use of concomitant medications that are sensitive substrates for CYP2D6 with a narrow\r\n             therapeutic index\r\n\r\n          -  Use of strong CYP3A4 inducers\r\n\r\n        Subprotocol C only:\r\n\r\n        Inclusion criteria\r\n\r\n          -  Subjects who are refractory to a novel antiandrogen therapy. Subjects must be\r\n             ineligible for or refuse taxane therapy.\r\n\r\n          -  Evidence of progressive disease, defined as 1 or more PCWG3 criteria: PSA level >/=1\r\n             ng/mL that has increased on at least 2 successive occasions at least 1 week apart,\r\n             nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications,\r\n             and/or appearance of 2 or more new lesions in bone scan Exclusion criteria\r\n\r\n          -  History or evidence of interstitial lung disease or active, non-infectious pneumonitis\r\n\r\n          -  Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a grade 3 or higher\r\n             immune-related adverse event prior to first day of dose\r\n\r\n        Subprotocol D only:\r\n\r\n        Inclusion criteria\r\n\r\n          -  Subjects may have had novel hormonal therapies (NHT; eg, abiraterone, enzalutamide,\r\n             apalutamide, or darolutamide) for prostate cancer, but no more than 1 NHT for\r\n             metastatic prostate cancer\r\n\r\n          -  Ineligible for or refuse taxane therapy\r\n      ","sponsor":"Amgen","sponsor_type":"Industry","conditions":"Metastatic Castration-resistant Prostate Cancer","interventions":[{"intervention_type":"Drug","name":"Drug: AMG 160","description":"AMG 160 will be administered as an intravenous (IV) infusion."},{"intervention_type":"Drug","name":"Drug: Enzalutamide","description":"Enzalutamide will be administered orally."},{"intervention_type":"Drug","name":"Drug: Abiraterone","description":"Abiraterone will be administered orally."},{"intervention_type":"Drug","name":"Drug: AMG 404","description":"AMG 404 will be administered as an intravenous (IV) infusion."}],"outcomes":[{"outcome_type":"primary","measure":"Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs)","time_frame":"Up to 3 years","description":"The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of AMG 160. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of AMG 160 with an evaluable DLT endpoint.\r\nThe DLT endpoint is evaluable if either:\r\n1) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1."},{"outcome_type":"primary","measure":"Number of participants who experience one or more treatment-emergent adverse events (TEAEs)","time_frame":"Up to 3 years"},{"outcome_type":"primary","measure":"Number of participants who experience one or more treatment-related adverse events","time_frame":"Up to 3 years"},{"outcome_type":"primary","measure":"Number of participants who experience a clinically significant change in vital signs","time_frame":"Up to 3 years"},{"outcome_type":"primary","measure":"Number of participants who experience a clinically significant change in clinical laboratory tests","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Number of participants who experience circulating tumor cell (CTC) response","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Number of participants who experience prostate-specific antigen (PSA) response rate","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Duration of response","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Progression-free survival","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Time to progression","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Time to subsequent therapy","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Maximum plasma concentration (Cmax)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Minimum plasma concentration (Cmin)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Area under the concentration-time curve (AUC)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Accumulation ratio based on area under the concentration-time curve (AUC)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Half-life (t1/2)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT)","time_frame":"Baseline up to 3 years"},{"outcome_type":"secondary","measure":"Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT)","time_frame":"Baseline to 3 years"},{"outcome_type":"secondary","measure":"Time to symptomatic skeletal events","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Concentration of alkaline phosphatase","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Concentration of lactate dehydrogenase (LDH)","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Concentration of hemoglobin","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Neutrophil-to-lymphocyte ratio","time_frame":"Up to 3 years"},{"outcome_type":"secondary","measure":"Concentration of N-telopeptide in the urine","time_frame":"Up to 3 years"}]}
{"nct_id":"NCT04527991","start_date":"2021-01-13","phase":"Phase 3","enrollment":600,"brief_title":"Study of Sacituzumab Govitecan-hziy (IMMU-132) Versus Treatment of Physician's Choice in Participants With Metastatic or Locally Advanced Unresectable Urothelial Cancer","official_title":"A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04)","primary_completion_date":"2023-06-30","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2024-01-31","last_update":"2021-09-10","description":"The primary objective of this study is to assess overall survival (OS) with sacituzumab govitecan-hziy in comparison with treatment of physician's choice (TPC) in participants with metastatic or locally advanced unresectable urothelial cancer (UC).","other_id":"IMMU-132-13","allocation":"Randomized","intervention_model":"Parallel Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria:\r\n\r\n          1. Individuals with histologically documented metastatic or locally advanced unresectable\r\n             UC defined as\r\n\r\n               -  Tumor (T) 4b, any node (N) or\r\n\r\n               -  Any T, N 2-3 Tumors of upper and lower urinary tract are permitted. Mixed\r\n                  histologic types are allowed if urothelial is the predominant histology.\r\n\r\n          2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.\r\n\r\n          3. Individuals with progression or recurrence following receipt of platinum-containing\r\n             regimen and anti programmed cell death protein 1/programmed death-ligand 1\r\n             (PD-1/PD-L1) therapy for metastatic or locally advanced unresectable disease will be\r\n             enrolled.\r\n\r\n               -  a. Individuals with recurrence or progression 12 months following completion of\r\n                  cisplatin-containing chemotherapy given in the neo-adjuvant/adjuvant setting may\r\n                  utilize that line of therapy to be eligible for the study. The 12-month period is\r\n                  counted from completion of surgical intervention or platinum therapy,\r\n                  respectively. These individuals must receive anti PD-1/PD-L1 therapy in the\r\n                  metastatic or locally advanced unresectable setting to be eligible.\r\n\r\n               -  b. Individuals who received either carboplatin or anti PD-1/PD-L1 therapy in the\r\n                  neo- adjuvant/adjuvant setting will not be able to count that line of therapy\r\n                  towards eligibility for the study.\r\n\r\n               -  c. Cisplatin ineligible individuals who meet one of the below criteria and who\r\n                  were treated with carboplatin in the metastatic or locally advanced unresectable\r\n                  settings may count that line of therapy towards eligibility. They must then have\r\n                  received anti PD-1/PD-L1 therapy in metastatic or locally advanced unresectable\r\n                  setting to be eligible for the study.\r\n\r\n                    -  Cisplatin ineligibility is defined as meeting one of the following criteria:\r\n\r\n                         -  1. Creatinine Clearance < 60 mL/min\r\n\r\n                         -  2. Grade  2 Audiometric Hearing Loss\r\n\r\n                         -  3. Grade  2 Peripheral Neuropathy\r\n\r\n                         -  4. New York Heart Association (NYHA) Class III heart failure\r\n\r\n                         -  5. ECOG PS  2\r\n\r\n               -  d. Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may be\r\n                  counted towards eligibility for the study\r\n\r\n               -  e. Individuals who received only concurrent chemoradiation for bladder\r\n                  preservation without further systemic therapy are not eligible to enroll in the\r\n                  study. The substitution of carboplatin for cisplatin does not constitute a new\r\n                  regimen provided no new chemotherapeutic agents were added to the regimen and no\r\n                  progression was noted prior to the change in platinum.\r\n\r\n          4. Individuals with previously treated brain metastases may participate in the study\r\n             provided they have stable CNS disease for at least 4 weeks prior to the first dose of\r\n             study drug and stabilization of all neurologic symptoms, have no evidence of new or\r\n             enlarging brain metastases, and are not using steroids >20 mg of prednisone (or\r\n             equivalent) daily for brain metastases for at least 7 days prior to first dose of the\r\n             study drug.\r\n\r\n          5. Adequate hematologic counts without transfusion or growth factor support within 1 week\r\n             of study drug initiation (hemoglobin  9 g/dL, absolute neutrophil count (ANC)\r\n             1,500/mm^3, and platelets 100,000/L).\r\n\r\n          6. Adequate hepatic function (bilirubin 1.5x institutional upper limit of normal (IULN),\r\n             aspartate aminotransferase (AST) and alanine aminotransferase (ALT)  2.5 x IULN or\r\n\r\n              5 x IULN if known liver metastases and serum albumin >3 g/dL).\r\n\r\n             Docetaxel will only be option in TPC arm for Individuals with a total bilirubin 1 x\r\n             IULN, and an AST and/or ALT 1.5x IULN if alkaline phosphatase is also >2.5 x IULN.\r\n\r\n          7. Creatinine clearance 30 mL/min as assessed by the Cockcroft-Gault equation or other\r\n             validated instruments (e.g. Modification of Diet in Renal Disease (MDRD) equation).\r\n\r\n          8. Females of childbearing potential must have a negative urine or serum pregnancy test\r\n             within 72 hours prior to receiving the first dose of study drug. If the urine test is\r\n             positive or cannot be confirmed as negative, a serum pregnancy test will be required.\r\n\r\n          9. Females of childbearing potential must be willing to use 2 methods of birth control or\r\n             be surgically sterile or abstain from heterosexual activity for the course of the\r\n             study through 6 months after the last dose of study drug. Individuals of childbearing\r\n             potential are those who have not been surgically sterilized or have not been free from\r\n             menses for >2 years.\r\n\r\n         10. Male individuals must agree to use an adequate method of contraception starting with\r\n             the first dose of study therapy through 3 months after the last dose of study therapy.\r\n\r\n        Exclusion Criteria:\r\n\r\n          1. Females who are pregnant or lactating.\r\n\r\n          2. Have had a prior anti-cancer monoclonal antibody (mAb)/ antibody-drug conjugate (ADC)\r\n             within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted\r\n             small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Individuals\r\n             participating in observational studies are eligible.\r\n\r\n          3. Have received prior chemotherapy for UC with all available SOC therapies in the\r\n             control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is\r\n             not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions\r\n             where vinflunine is an approved therapy).\r\n\r\n          4. Have not recovered (i.e.,  Grade 1) from AEs due to previously administered\r\n             chemotherapeutic agent.\r\n\r\n               -  Note: Individuals with  Grade 2 neuropathy or any grade of alopecia are an\r\n                  exception to this criterion and will qualify for the study.\r\n\r\n               -  Note: If Individuals received major surgery, they must have recovered adequately\r\n                  from the toxicity and/or complications from the intervention prior to starting\r\n                  study therapy.\r\n\r\n          5. Have previously received topoisomerase 1 inhibitors.\r\n\r\n          6. Have an active second malignancy.\r\n\r\n              Note: Individuals with a history of malignancy that have been completely treated and\r\n             with no evidence of active cancer for 3 years prior to enrollment, or individuals with\r\n             surgically cured tumors with low risk of recurrence are allowed to enroll in the study\r\n             after discussion with the medical monitor.\r\n\r\n          7. Have active cardiac disease, defined as:\r\n\r\n               -  Myocardial infarction or unstable angina pectoris within 6 months of C1D1.\r\n\r\n               -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or\r\n                  ventricular fibrillation), high-grade atrioventricular block, or other cardiac\r\n                  arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation\r\n                  that is well controlled with antiarrhythmic medication); history of QT interval\r\n                  prolongation.\r\n\r\n               -  NYHA Class III or greater congestive heart failure or left ventricular ejection\r\n                  fraction of <40%.\r\n\r\n          8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)\r\n             or gastrointestinal (GI) perforation within 6 months of enrollment.\r\n\r\n          9. Have an active serious infection requiring anti-infective therapy (Contact medical\r\n             monitor for clarification).\r\n\r\n         10. Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral\r\n             load and on medications that may interfere with SN-38 metabolism.\r\n\r\n         11. Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In individuals with a\r\n             history of HBV or HCV, individuals with a detectable viral load will be excluded.\r\n\r\n         12. Have other concurrent medical or psychiatric conditions that, in the investigator's\r\n             opinion, may be likely to confound study interpretation or prevent completion of study\r\n             procedures and follow-up examinations.\r\n\r\n         13. Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab\r\n             govitecan-hziy or unable or unwilling to receive the doses specified in the protocol.\r\n\r\n         14. Have inability to complete all specified study procedures for any reason.\r\n      ","sponsor":"Gilead Sciences","sponsor_type":"Industry","conditions":"Locally Advanced or Metastatic Unresectable Urothelial Cancer","interventions":[{"intervention_type":"Biological","name":"Biological: Sacituzumab Govitecan-hziy","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Paclitaxel","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Docetaxel","description":"Administered intravenously"},{"intervention_type":"Drug","name":"Drug: Vinflunine","description":"Administered intravenously"}],"outcomes":[{"outcome_type":"primary","measure":"Overall Survival (OS)","time_frame":"Up to 3.5 years","description":"OS is defined as time from the date of randomization to the date of death, regardless of cause."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) by Investigator Assessment","time_frame":"Up to 3.5 years","description":"PFS is defined as the time from the date of randomization to the date of the first objectively documented disease progression, per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria, as determined by investigator assessment, or death regardless of cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR)","time_frame":"Up to 3.5 years","description":"PFS is defined as the time from the date of randomization to the date of the first objectively documented disease progression, per RECIST v1.1 criteria as determined by BICR, or death regardless of cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by Investigator Assessment","time_frame":"Up to 3.5 years","description":"ORR is defined as the proportion of participants who achieved a complete response or partial response as best overall response (BOR). BOR is determined per RECIST 1.1 as determined by investigator assessment."},{"outcome_type":"secondary","measure":"Objective Response Rate (ORR) by BICR","time_frame":"Up to 3.5 years","description":"ORR is defined as the proportion of participants who achieved a complete response or partial response as best overall response (BOR). BOR is determined per RECIST 1.1 as determined by BICR."},{"outcome_type":"secondary","measure":"Clinical Benefit Rate (CBR) by Investigator Assessment","time_frame":"Up to 3.5 years","description":"CBR is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease for greater than or equal to 6 months to therapeutic intervention in a clinical study. CBR will be determined per RECIST v1.1 by investigator assessment."},{"outcome_type":"secondary","measure":"Clinical Benefit Rate (CBR) by BICR","time_frame":"Up to 3.5 years","description":"CBR is defined as the percentage of participants with advanced or metastatic cancer who have achieved complete response, partial response and stable disease for greater than or equal to 6 months to therapeutic intervention in a clinical study. CBR will be determined per RECIST v1.1 by BICR."},{"outcome_type":"secondary","measure":"Duration of Objective Tumor Response (DOR) by Investigator Assessment","time_frame":"Up to 3.5 years","description":"DOR is defined as the time from the date when the criteria is first met for a complete response or partial response to the first date that disease progression is documented per RECIST 1.1 as determined by investigator assessment, or date of death, whichever occurs first."},{"outcome_type":"secondary","measure":"Duration of Objective Tumor Response (DOR) by BICR","time_frame":"Up to 3.5 years","description":"DOR is defined as the time from the date when the criteria is first met for a complete response or partial response to the first date that disease progression is documented per RECIST 1.1 as determined by BICR, or date of death, whichever occurs first."},{"outcome_type":"secondary","measure":"Percentage of Participants Experiencing any Treatment Emergent Adverse Events","time_frame":"Up to 3.5 years"},{"outcome_type":"secondary","measure":"Percentage of Participants Experiencing any Serious Treatment Emergent Adverse Events","time_frame":"Up to 3.5 years"},{"outcome_type":"secondary","measure":"Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities","time_frame":"Up to 3.5 years"},{"outcome_type":"secondary","measure":"European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score","time_frame":"Up to 3.5 years","description":"The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant)."},{"outcome_type":"secondary","measure":"European Quality of Life 5-Dimensions 5 Levels Instrument (EuroQOL EQ-5D-5L) Score","time_frame":"Up to 3.5 years","description":"The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive part and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state.\r\nThe EQ-VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating \"the worst health you can imagine\" and 100 indicating \"the best health you can imagine.\" Higher scores of EQ VAS indicate better health."}]}
{"nct_id":"NCT04579380","start_date":"2021-01-11","phase":"Phase 2","enrollment":270,"brief_title":"Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations","official_title":"A Phase 2 Basket Study of Tucatinib in Combination With Trastuzumab in Subjects With Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations","primary_completion_date":"2023-01-31","study_type":"Interventional","rec_status":"Recruiting","completion_date":"2025-05-31","last_update":"2021-09-21","description":"This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant. The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.","other_id":"SGNTUC-019","allocation":"N/A","intervention_model":"Single Group Assignment","primary_purpose":"Treatment","masking_description":"None (Open Label)","sampling_method":"","gender":"All","minimum_age":18,"population":"","criteria":"\n        Inclusion Criteria\r\n\r\n          -  Histologically or cytologically confirmed diagnosis of locally-advanced unresectable\r\n             or metastatic solid tumor, including primary brain tumors\r\n\r\n          -  Participants with non-squamous NSCLC must have progressed during or after standard\r\n             treatment or for which no standard treatment is available\r\n\r\n          -  Participants with other disease types must have progressed during or after 1 prior\r\n             line of systemic therapy for locally-advanced unresectable or metastatic disease\r\n\r\n          -  Disease progression during or after, or intolerance of, the most recent line of\r\n             systemic therapy\r\n\r\n          -  Disease demonstrating HER2 alterations (overexpression/amplification or HER2\r\n             activating mutations), as determined by local or central testing processed in a\r\n             Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for\r\n             Standardization (ISO) accredited laboratory, according to one of the following:\r\n\r\n               -  HER2 overexpression/amplification from fresh or archival tumor tissue or blood\r\n\r\n               -  Known activating HER2 mutations detected in fresh or archival tumor tissue or\r\n                  blood\r\n\r\n          -  Have measurable disease per RECIST v1.1 criteria according to investigator assessment\r\n\r\n          -  Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\r\n\r\n        Exclusion Criteria\r\n\r\n          -  Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma,\r\n             or CRC whose disease shows HER2 amplification/overexpression.\r\n\r\n          -  Previous treatment with HER2-directed therapy; participants with uterine serous\r\n             carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without\r\n             HER2-overexpression/amplification may have received prior trastuzumab\r\n\r\n          -  Known hypersensitivity to any component of the drug formulation of tucatinib or\r\n             trastuzumab (drug substance, excipients, murine proteins), or any component of the\r\n             drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer\r\n\r\n          -  History of exposure to a 360 mg/m doxorubicin-equivalent or >720 mg/m^2\r\n             epirubicin-equivalent cumulative dose of anthracyclines\r\n\r\n          -  Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or\r\n             experimental agent within 3 weeks of first dose of study treatment or are currently\r\n             participating in another interventional clinical trial.\r\n\r\n        There are additional inclusion and exclusion criteria. The study center will determine if\r\n        criteria for participation are met.\r\n      ","sponsor":"Seagen Inc.","sponsor_type":"Industry","conditions":"Breast Neoplasms|Carcinoma, Non-Small-Cell Lung|Urologic Neoplasms|Biliary Tract Neoplasms|Uterine Cervical Neoplasms|Uterine Neoplasms","interventions":[{"intervention_type":"Drug","name":"Drug: tucatinib","description":"300 mg orally twice daily"},{"intervention_type":"Drug","name":"Drug: trastuzumab","description":"Given into the vein (intravenously; IV). 8mg/kg IV on Cycle 1 Day 1, and 6mg/kg every 21 days starting on Cycle 2 Day 1"},{"intervention_type":"Drug","name":"Drug: fulvestrant","description":"Given into the muscle (intramuscular; IM) once every 4 weeks starting from Cycle 1 Day 1, plus one dose on Cycle 1 Day 15. Only administered to participants with hormone-receptor positive breast cancer."}],"outcomes":[{"outcome_type":"primary","measure":"Confirmed objective response rate (cORR) per investigator assessment","time_frame":"From start of treatment up to approximately 2 years","description":"cORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1"},{"outcome_type":"secondary","measure":"Disease control rate (DCR) per investigator assessment","time_frame":"From start of treatment up to approximately 2 years","description":"DCR is defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease according to RECIST v1.1"},{"outcome_type":"secondary","measure":"Duration of response (DOR) per investigator assessment","time_frame":"From start of treatment up to approximately 2 years","description":"DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Progression-free survival (PFS) per investigator assessment","time_frame":"From start of treatment up to approximately 2 years","description":"PFS is defined as the time from the date of treatment initiation to the date of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first."},{"outcome_type":"secondary","measure":"Overall survival (OS)","time_frame":"From start of treatment up to approximately 4 years","description":"OS is defined as the time from treatment initiation to death due to any cause."},{"outcome_type":"secondary","measure":"Incidence of adverse events (AEs)","time_frame":"From start of treatment up to approximately 2 years","description":"Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment."},{"outcome_type":"secondary","measure":"Incidence of laboratory abnormalities","time_frame":"From start of treatment up to approximately 2 years","description":"To be summarized using descriptive statistics."},{"outcome_type":"secondary","measure":"Incidence of dose alterations","time_frame":"From start of treatment up to approximately 2 years"},{"outcome_type":"secondary","measure":"Maximum concentration (Cmax)","time_frame":"Approximately 4 months, during first 6 cycles of treatment","description":"To be summarized using descriptive statistics."},{"outcome_type":"secondary","measure":"Trough concentration (Ctrough)","time_frame":"Approximately 4 months, during first 6 cycles of treatment","description":"To be summarized using descriptive statistics."}]}