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)
MK-5684-004: A Phase 3, Randomized, Open-label Study of Opevesostat Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment With One Next-generation Hormonal Agent (NHA) (OMAHA-004)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests opevesostat plus daily steroid medicines against abiraterone acetate or enzalutamide. It is for people whose prostate cancer has spread and worsened despite treatment to lower testosterone and one newer hormone drug. Researchers will compare safety and how long people live.
The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypothesis is that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to overall survival (OS), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have prostate cancer confirmed by a tissue or cell test, with no small cell cancer. Scans must show that the cancer has spread to distant parts of the body.
- Cancer worsened within 6 months before screening while on treatment to lower testosterone, or after surgery to remove both testicles.
- Cancer worsened during or after one newer hormone drug taken for at least 8 weeks, or 14 weeks if cancer in the bones worsened.
- Have already taken a PARP inhibitor, a type of cancer drug, or could not take it or chose not to take it.
- Be on treatment to lower testosterone, with a testosterone level below 50 ng/dL.
- Be fully active or able to do light work, and have organs that work well enough for the study.
- Provide a fresh tumor sample from soft tissue. The area must not have had radiation unless the tumor there is growing.
- Have recovered from most side effects of past cancer treatment. Some ongoing side effects are allowed.
Who can't join
- Have a stomach or bowel condition, cannot swallow pills, have a history of pituitary gland problems, have poorly controlled diabetes, or have major blood salt problems.
- Have low or uncontrolled high blood pressure, certain heart or blood vessel problems, certain abnormal heart rhythms, or a personal or family history of long QT syndrome, a heart rhythm condition.
- Had a seizure within 6 months before consent, or a condition that raises seizure risk within 12 months before joining.
- Have had taxane chemotherapy for prostate cancer that has spread and resists testosterone-lowering treatment, or have not recovered enough from major surgery.
- Have recently had certain cancer treatments, radiation, study drugs or devices, or a live vaccine. Some other medicines and unstable thyroid hormone doses also rule people out.
- Are allergic to any listed study medicine or its ingredients, or have a bone scan that would make new areas of cancer too hard to see.
- Have another cancer that is growing or needed treatment in the past 3 years, or active cancer in the brain, spinal cord, or their lining. Some treated, stable brain tumors are allowed.
- Have certain immune system problems, take medicines that suppress immunity, have an autoimmune disease needing whole-body treatment in the past 2 years, have an infection needing whole-body treatment, or have active hepatitis B and C together.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology * Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening * Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI) * Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer \[mHSPC\] or non-metastatic hormone-sensitive prostate cancer \[nmHSPC\]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer \[mCRPC\] or non-metastatic castration-resistant prostate cancer \[nmCRPC\]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel * Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment * Has ongoing androgen deprivation therapy (ADT) with serum testosterone \<50 ng/dL (\<1.7 nM) * Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 10 days before randomization * Has adequate organ function * Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed * 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 before randomization * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy or ≤Grade 2 osteopenia/osteoporosis are eligible * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has presence of gastrointestinal condition * Is unable to swallow capsules/tablets * Has history of pituitary dysfunction * Has poorly controlled diabetes mellitus * Has clinically significant abnormal serum potassium or sodium level * Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) \<110 mmHg, or uncontrolled hypertension: systolic BP ≥160mmHg or diastolic blood BP ≥90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy * Has a history of active or unstable cardio/cerebrovascular disease, including thromboembolic events * History or family history of long QTc syndrome * Has a history of seizure(s) within 6 months before providing documented informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment * Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place * Has received a taxane-based chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) * Has not adequately recovered from major surgery or have ongoing surgical complications * Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures * Participants on an unstable dose of thyroid hormone therapy, as judged by the investigator, within 6 months before the start of the study intervention * Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids * Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention * Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention * Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat * Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention * Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed * Active infection requiring systemic therapy * Has concurrent active Hepatitis B virus and Hepatitis C virus infection
Study sites (63)
AZ
- The University of Arizona Cancer Center - North Campus ( Site 0073) · Tucson, AZ 85719Study Coordinator · Study contact · 520-626-1068More trials in Tucson
CA
- CHAO Family Comprehensive Cancer Center and Ambulatory Care ( Site 0120) · Irvine, CA 92612Study Coordinator · Study contact · 714-456-7890More trials in Irvine
- UCLA Hematology/Oncology - Santa Monica ( Site 0044) · Los Angeles, CA 90404Study Coordinator · Study contact · 310-210-9001More trials in Los Angeles
- University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040) · Orange, CA 92868Study Coordinator · Study contact · 714-456-7890More trials in Orange
- Stanford Cancer Center ( Site 0036) · Palo Alto, CA 94304Study Coordinator · Study contact · 650-725-2078More trials in Palo Alto
- Emad Ibrahim,MD,INC. ( Site 0012) · Redlands, CA 92373More trials in Redlands
- Kaiser Permanente Riverside Medical Center ( Site 0099) · Riverside, CA 92505Study Coordinator · Study contact · 951-353-3323More trials in Riverside
- University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114) · Sacramento, CA 95817Study Coordinator · Study contact · 916-734-3772More trials in Sacramento
- San Francisco VA Health Care System ( Site 0093) · San Francisco, CA 94121Study Coordinator · Study contact · 415-221-4810 x23022More trials in San Francisco
- Kaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101) · Vallejo, CA 94589More trials in Vallejo
CO
- University of Colorado Anschutz Medical Campus ( Site 0046) · Aurora, CO 80045Study Coordinator · Study contact · 302-290-3598More trials in Aurora
- UCHealth Highlands Ranch Hospital ( Site 0111) · Highlands Ranch, CO 80129Study Coordinator · Study contact · 720-516-1000More trials in Highlands Ranch
- Colorado Clinical Research ( Site 0067) · Lakewood, CO 80228Study Coordinator · Study contact · 303-885-9828More trials in Lakewood
- University of Colorado Health - Lone Tree Medical Center ( Site 0112) · Lone Tree, CO 80124Study Coordinator · Study contact · 720-470-9107More trials in Lone Tree
CT
- Yale-New Haven Hospital-Yale Cancer Center ( Site 0064) · New Haven, CT 06510Study Coordinator · Study contact · 203-737-8076More trials in New Haven
DC
- MedStar Washington Hospital Center ( Site 0103) · Washington D.C., DC 20010Study Coordinator · Study contact · 202-877-6583More trials in Washington D.C.
FL
- Florida Cancer Specialists - South ( Site 7003) · Fort Myers, FL 33901More trials in Fort Myers
- Mount Sinai Braman Comprehensive Cancer Center ( Site 0107) · Miami Beach, FL 33140Study Coordinator · Study contact · 305-535-3300More trials in Miami Beach
- Memorial Hospital West-Memorial Cancer Institute ( Site 0109) · Pembroke Pines, FL 33028Study Coordinator · Study contact · 954-265-4325More trials in Pembroke Pines
GA
- Northside Hospital-Northside Hospital Oncology Network ( Site 0100) · Atlanta, GA 30342Study Coordinator · Study contact · 770-590-8311More trials in Atlanta
IL
- Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0074) · Elmhurst, IL 60126More trials in Elmhurst
- Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0075) · Naperville, IL 60540More trials in Naperville
- Illinois Cancer Care ( Site 0104) · Peoria, IL 61615Study Coordinator · Study contact · 309-240-6388More trials in Peoria
IN
- Urology of Indiana - Carmel ( Site 0055) · Carmel, IN 46032Study Coordinator · Study contact · 317-564-5158More trials in Carmel
KY
- University of Kentucky Chandler Medical Center ( Site 0048) · Lexington, KY 40536More trials in Lexington
MD
- Baltimore Veterans Affairs Medical Center ( Site 0069) · Baltimore, MD 21201Study Coordinator · Study contact · 1-410-7074-011More trials in Baltimore
- Greenebaum Comprehensive Cancer Center ( Site 0049) · Baltimore, MD 21201Study Coordinator · Study contact · 410-707-4011More trials in Baltimore
- Chesapeake Urology ( Site 0009) · Towson, MD 21204Study Coordinator · Study contact · 410-825-5454More trials in Towson
MI
- Henry Ford Hospital ( Site 0015) · Detroit, MI 48202Study Coordinator · Study contact · 313-916-1784More trials in Detroit
- Cancer and Hematology Centers of Western Michigan ( Site 0005) · Grand Rapids, MI 49503Study Coordinator · Study contact · 616-399-6500More trials in Grand Rapids
MN
- Avera Cancer Institute - Marshall ( Site 0122) · Marshall, MN 56258Study Coordinator · Study contact · 605-601-1830More trials in Marshall
- HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0072) · Saint Louis Park, MN 55426Study Coordinator · Study contact · 952-977-5555More trials in Saint Louis Park
- HealthPartners Cancer Research Center-HealthPartners Cancer Center at Regions Hospital ( Site 0092) · Saint Paul, MN 55101Study Coordinator · Study contact · 651-254-1517More trials in Saint Paul
MT
- St. Vincent Frontier Cancer Center-Research ( Site 0037) · Billings, MT 59102Study Coordinator · Study contact · 406-238-6685More trials in Billings
NE
- Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0026) · Omaha, NE 68130Study Coordinator · Study contact · 402-334-4773More trials in Omaha
NJ
- Rutgers Cancer Institute of New Jersey ( Site 0033) · New Brunswick, NJ 08903Study Coordinator · Study contact · 732-235-2465More trials in New Brunswick
NV
- OptumCare Cancer Care-Research Department ( Site 0078) · Las Vegas, NV 89102Study Coordinator · Study contact · 702-724-8787More trials in Las Vegas
- Comprehensive Cancer Centers of Nevada ( Site 0010) · Las Vegas, NV 89148Study Coordinator · Study contact · 702-952-3449More trials in Las Vegas
NY
- Associated Medical Professionals - Urology ( Site 0081) · Syracuse, NY 13210Study Coordinator · Study contact · 315-478-4185More trials in Syracuse
OH
- University Hospitals Cleveland Medical Center ( Site 0043) · Cleveland, OH 44106Study Coordinator · Study contact · 216-844-3951More trials in Cleveland
- Central Ohio Urology Group - Gahanna ( Site 0098) · Gahanna, OH 43230More trials in Gahanna
- Genesis Healthcare System ( Site 0102) · Zanesville, OH 43701More trials in Zanesville
PA
- MidLantic urology ( Site 0022) · Bala-Cynwyd, PA 19004Study Coordinator · Study contact · 610-667-3020More trials in Bala-Cynwyd
- Fox Chase Cancer Center ( Site 0076) · Philadelphia, PA 19111Study Coordinator · Study contact · 267-512-1098More trials in Philadelphia
SC
- Ralph H. Johnson VA Health Care System (RHJVAHCS)-Urology ( Site 0083) · Charleston, SC 29401Study Coordinator · Study contact · 843-792-7888More trials in Charleston
SD
- Avera Cancer Institute - Aberdeen ( Site 0123) · Aberdeen, SD 57401Study Coordinator · Study contact · 605-601-1830More trials in Aberdeen
- Avera Cancer Institute - Mitchell ( Site 0121) · Mitchell, SD 57301Study Coordinator · Study contact · 605-601-1830More trials in Mitchell
- Avera Cancer Institute - Pierre ( Site 0118) · Pierre, SD 57501Study Coordinator · Study contact · 605-224-3370More trials in Pierre
- Avera Cancer Institute- Research ( Site 0094) · Sioux Falls, SD 57105Study Coordinator · Study contact · 605-322-6900More trials in Sioux Falls
- Avera Cancer Institute - Yankton ( Site 0117) · Yankton, SD 57078Study Coordinator · Study contact · 605-655-1800More trials in Yankton
TN
- The West Clinic, PLLC dba West Cancer Center ( Site 0063) · Germantown, TN 38138Study Coordinator · Study contact · 901-683-0055More trials in Germantown
TX
- Texas Oncology - Central/South Texas ( Site 8003) · Austin, TX 78731Study Coordinator · Study contact · 512-427-9400More trials in Austin
- Cancer Clinics of North Texas ( Site 0077) · Dallas, TX 75243More trials in Dallas
- Texas Oncology - DFW ( Site 8001) · Dallas, TX 75246Study Coordinator · Study contact · 214-370-1000More trials in Dallas
- Texas Oncology - Gulf Coast ( Site 8002) · Houston, TX 77024Study Coordinator · Study contact · 713-467-1722More trials in Houston
VA
- University of Virginia Health System ( Site 0054) · Charlottesville, VA 22908Study Coordinator · Study contact · 434-327-3029More trials in Charlottesville
- Inova Schar Cancer Institute ( Site 0017) · Fairfax, VA 22031Study Coordinator · Study contact · 571-472-1180More trials in Fairfax
- Virginia Cancer Specialists (VCS) ( Site 8004) · Fairfax, VA 22031Study Coordinator · Study contact · 844-482-4812More trials in Fairfax
- VCU Health Adult Outpatient Pavillion ( Site 0061) · Richmond, VA 23219Study Coordinator · Study contact · 804-628-6430More trials in Richmond
- Blue Ridge Cancer Care ( Site 0004) · Roanoke, VA 24014Study Coordinator · Study contact · 540-982-0237More trials in Roanoke
WA
- Spokane Urology ( Site 0035) · Spokane, WA 99202Study Coordinator · Study contact · 509-747-3147More trials in Spokane
- Northwest Cancer Specialists (Compass Oncology) ( Site 8008) · Vancouver, WA 98684More trials in Vancouver
WI
- Medical College of Wisconsin ( Site 0020) · Milwaukee, WI 53226Study Coordinator · Study contact · 414-805-6700More trials in Milwaukee