Actively Recruiting
MK-5684-004 A Randomized Study Comparing Opevesostat Plus Hormone Replacement Therapy to Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer After Prior Hormonal Therapy
Led by Merck Sharp & Dohme LLC · Updated on 2026-06-03
1314
Participants Needed
327
Research Sites
133 weeks
Total Duration
On this page
Sponsors
M
Merck Sharp & Dohme LLC
Lead Sponsor
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Orion Corporation, Orion Pharma
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the effectiveness and safety of opevesostat combined with hormone replacement therapy HRT compared to alternative treatments, abiraterone acetate or enzalutamide, in adults with metastatic castration-resistant prostate cancer mCRPC who have previously been treated with one next-generation hormonal agent NHA. The study aims to determine if opevesostat improves the time participants live without their cancer worsening on scans, considering both those with and without certain androgen receptor mutations. Overall survival was also added as a secondary outcome to be assessed over a longer period. Participants are randomly assigned to one of two treatment groups. One group receives oral opevesostat twice daily along with daily dexamethasone and fludrocortisone acetate, continuing until their disease progresses. Hydrocortisone is available as a rescue medication if needed. The other group receives either abiraterone acetate plus prednisone or enzalutamide daily, also until disease progression. The study is open-label, meaning both researchers and participants know which treatment is given. During the study, participants will have regular assessments including imaging scans to monitor cancer progression, blood tests, and questionnaires evaluating quality of life and symptoms. Researchers will track the time until cancer worsens on imaging, overall survival, response rates, pain progression, and side effects. These evaluations may continue for up to approximately 82 months. Safety monitoring and treatment adherence will be followed throughout the study period.
CONDITIONS
Brief Title
A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed adenocarcinoma of the prostate without small cell histology
- Prostate cancer progression within 6 months before screening while on androgen deprivation therapy or post bilateral orchiectomy
- Evidence of distant metastatic disease shown by bone scan or CT/MRI
- Disease progressed during or after treatment with one next-generation hormonal agent for hormone-sensitive or castration-resistant prostate cancer, with minimum treatment durations
- Prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or deemed ineligible/refused PARPi
- Ongoing androgen deprivation therapy with serum testosterone below 50 ng/dL
- Eastern Clinical Oncology Group (ECOG) performance status of 0 or 1 within 10 days before randomization
- Adequate organ function
- Provided tumor tissue from fresh biopsy not previously irradiated
- Hepatitis B surface antigen positive patients eligible if on antiviral therapy with undetectable viral load
- Hepatitis C patients eligible if viral load undetectable at screening
- Recovered to Grade 1 or baseline from prior adverse events, with exceptions for certain endocrine-related or neuropathy/osteopenia conditions
- Well-controlled HIV infection on antiretroviral therapy
You will not qualify if you...
- Presence of gastrointestinal condition
- Unable to swallow capsules or tablets
- History of pituitary dysfunction
- Poorly controlled diabetes mellitus
- Abnormal serum potassium or sodium levels
- Hypotension or uncontrolled hypertension despite therapy
- Active or unstable cardio/cerebrovascular disease including thromboembolic events
- History or family history of long QTc syndrome
- Recent seizures or conditions predisposing to seizures
- Clinically significant ventricular arrhythmias or heart block without pacemaker
- Prior taxane-based chemotherapy for metastatic castration-resistant prostate cancer
- Incomplete recovery from major surgery or ongoing surgical complications
- Current treatment with CYP450-inducing antiepileptic drugs
- Unstable thyroid hormone therapy within 6 months before study
- Recent radiotherapy or radiation-related toxicities needing corticosteroids
- Recent systemic anticancer therapy including investigational agents
- Recent use of strong CYP3A4 inducers or P-glycoprotein inhibitors
- Recent targeted small molecule or NHA therapy
- Recent live or live-attenuated vaccination
- Recent investigational agent or device use
- Known hypersensitivity to study drugs or excipients
- "Superscan" bone scan preventing evaluation of metastases
- Active progressing additional malignancy needing treatment within 3 years
- Diagnosis of immunodeficiency or recent high-dose immunosuppressive therapy
- Known active central nervous system metastases or carcinomatous meningitis, with exceptions for stable treated brain metastases
- Active autoimmune disease requiring systemic treatment in past 2 years
- Active infection requiring systemic therapy
- Concurrent active Hepatitis B and C infection
Research Team
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