Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

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.

Exclusion Criteria

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: Opevesostat
    Oral Tablet
    Other names:
    • MK-5684
  • Drug: Fludrocortisone acetate
    Oral Tablet
  • Drug: Dexamethasone
    Oral Tablet
Experimental
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.
  • Drug: Opevesostat
    Oral Tablet
    Other names:
    • MK-5684
  • Drug: Olaparib
    Oral Tablet
    Other names:
    • LYNPARZA®
  • Drug: Fludrocortisone acetate
    Oral Tablet
  • Drug: Dexamethasone
    Oral Tablet
Experimental
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.
  • Drug: Opevesostat
    Oral Tablet
    Other names:
    • MK-5684
  • Drug: Docetaxel
    IV Infusion
    Other names:
    • TAXOTERE®
  • Drug: Fludrocortisone acetate
    Oral Tablet
  • Drug: Dexamethasone
    Oral Tablet
  • Drug: Prednisone
    Oral Tablet
Experimental
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.
  • Drug: Opevesostat
    Oral Tablet
    Other names:
    • MK-5684
  • Drug: Cabazitaxel
    IV Infusion
    Other names:
    • JEVTANA®
  • Drug: Fludrocortisone acetate
    Oral Tablet
  • Drug: Dexamethasone
    Oral Tablet
  • Drug: Prednisone
    Oral Tablet

Recruiting Locations

UCSD Moores Cancer Center ( Site 0039)
La Jolla, California 92037
Contact:
Study Coordinator
858-822-6100

UCLA Hematology/Oncology - Santa Monica ( Site 0044)
Los Angeles, California 90404
Contact:
Study Coordinator
310-825-2631

University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)
Miami, Florida 33136
Contact:
Study Coordinator
305-243-1543

University Hospitals Cleveland Medical Center ( Site 0043)
Cleveland, Ohio 44106
Contact:
Study Coordinator
216-844-3951

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)
Milwaukee, Wisconsin 53226
Contact:
Study Coordinator
414-955-8296

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.