MK-5684-01A Substudy: A Phase 1/2 Umbrella Substudy of MK-5684-U01 Master Protocol to Evaluate the Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 157
- 主要终点
- Number of participants who discontinue study intervention due to an AE
研究概览
简要总结
Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01).
The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.
This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.
- •Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.
- •Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.
- •Current evidence of metastatic disease.
- •Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.
- •Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization.
- •Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to <Grade 1 or baseline.
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
- •Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •History of pituitary dysfunction.
- •Poorly controlled diabetes mellitus.
- •Active or unstable cardio/cerebro-vascular disease, including thromboembolic events and history of stroke or transient ischemic attack within 6 months before the first dose of study intervention, history of myocardial infarction within 6 months before the first dose of study intervention, New York Heart Association Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina
- •History or family history of long corrected QT interval (QTc) syndrome.
- •Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.
- •History or current condition of adrenal insufficiency.
- •History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.
- •Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.
- •Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
- •Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids.
- •Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed.
- •Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Active autoimmune disease that has required systemic treatment in the past 2 years.
- •Active infection requiring systemic therapy.
- •Concurrent active HBV or HCV infections.
研究组 & 干预措施
Arm A1: Opevesostat
Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.
干预措施: Opevesostat (Drug)
Arm A1: Opevesostat
Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.
干预措施: Fludrocortisone acetate (Drug)
Arm A1: Opevesostat
Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.
干预措施: Dexamethasone (Drug)
Arm A3: Docetaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Dexamethasone (Drug)
Arm A3: Docetaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Prednisone (Drug)
Arm A4: Cabazitaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Cabazitaxel (Drug)
Arm A3: Docetaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Opevesostat (Drug)
Arm A4: Cabazitaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Opevesostat (Drug)
Arm A2: Olaparib + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.
干预措施: Fludrocortisone acetate (Drug)
Arm A2: Olaparib + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.
干预措施: Dexamethasone (Drug)
Arm A3: Docetaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Fludrocortisone acetate (Drug)
Arm A3: Docetaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Docetaxel (Drug)
Arm A4: Cabazitaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Fludrocortisone acetate (Drug)
Arm A2: Olaparib + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.
干预措施: Opevesostat (Drug)
Arm A2: Olaparib + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.
干预措施: Olaparib (Drug)
Arm A4: Cabazitaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Prednisone (Drug)
Arm A4: Cabazitaxel + Opevesostat
Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of participants who discontinue study intervention due to an AE
时间窗: Up to approximately 46 months
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 one or more dose-limiting toxicities (DLTs)
时间窗: Up to approximately 28 days
The following events, if considered drug related by the investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not laboratory value); Grade 4 hematologic toxicity lasting \>7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia associated with clinically significant bleeding); Any nonhematologic adverse event (AE) \>Grade 3 in severity should be considered a DLT (with exceptions); Any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); Febrile neutropenia Grade 3 or Grade 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 28 days due to study intervention-related toxicity; Missing \>25% of study intervention doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity.
Number of participants who experience one or more adverse events (AEs)
时间窗: Up to approximately 46 months
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.
Prostate-specific antigen (PSA) response rate
时间窗: Up to approximately 46 months
The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level will be confirmed by an additional PSA evaluation performed ≥3 weeks from the original response per Prostate Cancer Working Group (PCWG) criteria.
次要结局
- Duration of response (DOR)(Up to approximately 46 months)
- Objective response rate (ORR)(Up to approximately 46 months)
- Radiographic progression-free survival (rPFS)(Up to approximately 46 months)
- Overall survival (OS)(Up to approximately 46 months)
- Time to first subsequent anticancer therapy (TFST)(Up to approximately 46 months)
- Time to pain progression (TTPP)(Up to approximately 46 months)