Recruiting
Phase 1/Phase 2
Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A)
Condition(s) studied
Prostatic Neoplasms, Castration-Resistant
Investigational drug(s) / intervention(s)
OpevesostatOlaparibDocetaxelCabazitaxelFludrocortisone acetateDexamethasonePrednisone
Opevesostat: Oral Tablet
Olaparib: Oral Tablet
Docetaxel: IV Infusion
Cabazitaxel: IV Infusion
Fludrocortisone acetate: Oral Tablet
Dexamethasone: Oral Tablet
Prednisone: Oral Tablet
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- Number of participants who experience one or more dose-limiting toxicities (DLTs) — 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) — 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 discontinue study intervention due to an AE — 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 — 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.
Trial sites (77)
| Facility | City | Region | Status |
| UCSD Moores Cancer Center ( Site 0039) |
La Jolla |
California |
Recruiting |
| UCLA Hematology/Oncology - Santa Monica ( Site 0044) |
Los Angeles |
California |
Recruiting |
| University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051) |
Miami |
Florida |
Recruiting |
| University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049) |
Baltimore |
Maryland |
Active Not Recruiting |
| Rutgers Cancer Institute of New Jersey ( Site 0033) |
New Brunswick |
New Jersey |
Active Not Recruiting |
| University Hospitals Cleveland Medical Center ( Site 0043) |
Cleveland |
Ohio |
Recruiting |
| MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020) |
Milwaukee |
Wisconsin |
Recruiting |
| Macquarie University-MQ Health Clinical Trials Unit ( Site 0108) |
Macquarie University |
New South Wales |
Recruiting |
| Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107) |
Greenslopes |
Queensland |
Recruiting |
| Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110) |
Melbourne |
Victoria |
Recruiting |
| Centre Hospitalier de l'Université de Montréal ( Site 0200) |
Montreal |
Quebec |
Recruiting |
| Jewish General Hospital ( Site 0206) |
Montreal |
Quebec |
Recruiting |
| Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0207) |
Québec |
Quebec |
Recruiting |
| CIDO SpA-Oncology ( Site 0302) |
Temuco |
Biobio |
Active Not Recruiting |
| Clinica Universidad Catolica del Maule-Oncology ( Site 0304) |
Talca |
Maule Region |
Recruiting |
| FALP ( Site 0301) |
Santiago |
Region M. de Santiago |
Active Not Recruiting |
| Pontificia Universidad Catolica de Chile ( Site 0303) |
Santiago |
Region M. de Santiago |
Recruiting |
| Bradfordhill ( Site 0300) |
Santiago |
Region M. de Santiago |
Recruiting |
| FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0406) |
Bogotá |
Bogota D.C. |
Recruiting |
| Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402) |
Bogotá |
Bogota D.C. |
Recruiting |
| Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400) |
Valledupar |
Cesar Department |
Recruiting |
| IMAT S.A.S ( Site 0404) |
Montería |
Departamento de Córdoba |
Recruiting |
| Fundación Valle del Lili-Oncology CIC ( Site 0403) |
Cali |
Valle del Cauca Department |
Recruiting |
| Herlev and Gentofte Hospital ( Site 0501) |
Copenhagen |
Capital Region |
Recruiting |
| Aalborg Universitetshospital, Syd ( Site 0503) |
Aalborg |
North Denmark |
Recruiting |
| Vaasan Keskussairaala ( Site 0603) |
Vaasa |
Pohjanmaa |
Recruiting |
| Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) ( Site 0604) |
Helsinki |
Uusimaa |
Recruiting |
| Docrates Syöpäsairaala ( Site 0602) |
Helsinki |
Uusimaa |
Recruiting |
| Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0703) |
Bordeaux |
Aquitaine |
Recruiting |
| Hopitaux Universitaires de Strasbourg ( Site 0700) |
Strasbourg |
Bas-Rhin |
Recruiting |
| Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702) |
Paris |
France |
Recruiting |
| Gustave Roussy ( Site 0701) |
Villejuif |
Île-de-France Region |
Recruiting |
| Universitaetsklinikum Heidelberg ( Site 0805) |
Heidelberg |
Baden-Wurttemberg |
Recruiting |
| Universitaetsklinikum Tuebingen-Urologie ( Site 0801) |
Tübingen |
Baden-Wurttemberg |
Recruiting |
| klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0802) |
Munich |
Bavaria |
Recruiting |
| Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800) |
Berlin |
Germany |
Active Not Recruiting |
| Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804) |
Hamburg |
Germany |
Recruiting |
| St. Vincent's University Hospital ( Site 0901) |
Dublin |
Dublin |
Recruiting |
| Cork University Hospital ( Site 0902) |
Cork |
Ireland |
Recruiting |
| Tallaght University Hospital ( Site 0900) |
Dublin |
Ireland |
Recruiting |
+ 37 more sites — see the full list on the official registry below.