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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)

NCT06353386 · Merck Sharp & Dohme LLC
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Official title
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)
About this study
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 criteria
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
Enrollment target: 220 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-05-20
Estimated completion: 2029-01-15
Last updated: 2026-05-26
Interventions
Drug: OpevesostatDrug: OlaparibDrug: DocetaxelDrug: CabazitaxelDrug: Fludrocortisone acetateDrug: DexamethasoneDrug: Prednisone
Primary outcomes
  • Number of participants who experience one or more dose-limiting toxicities (DLTs) (Up to approximately 28 days)
  • Number of participants who experience one or more adverse events (AEs) (Up to approximately 46 months)
  • Number of participants who discontinue study intervention due to an AE (Up to approximately 46 months)
Sponsor
Merck Sharp & Dohme LLC · industry
With: Orion Corporation, Orion Pharma
Contacts & investigators
ContactToll Free Number · contact · Trialsites@msd.com · 1-888-577-8839
InvestigatorMedical Director · study_director, Merck Sharp & Dohme LLC
All locations (77)
UCSD Moores Cancer Center ( Site 0039)Recruiting
La Jolla, California, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0044)Recruiting
Los Angeles, California, United States
University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)Recruiting
Miami, Florida, United States
University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049)Active Not Recruiting
Baltimore, Maryland, United States
Rutgers Cancer Institute of New Jersey ( Site 0033)Active Not Recruiting
New Brunswick, New Jersey, United States
University Hospitals Cleveland Medical Center ( Site 0043)Recruiting
Cleveland, Ohio, United States
MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)Recruiting
Milwaukee, Wisconsin, United States
Macquarie University-MQ Health Clinical Trials Unit ( Site 0108)Recruiting
Macquarie University, New South Wales, Australia
Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107)Recruiting
Greenslopes, Queensland, Australia
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110)Recruiting
Melbourne, Victoria, Australia
Centre Hospitalier de l'Université de Montréal ( Site 0200)Recruiting
Montreal, Quebec, Canada
Jewish General Hospital ( Site 0206)Recruiting
Montreal, Quebec, Canada
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0207)Recruiting
Québec, Quebec, Canada
CIDO SpA-Oncology ( Site 0302)Active Not Recruiting
Temuco, Biobio, Chile
Clinica Universidad Catolica del Maule-Oncology ( Site 0304)Recruiting
Talca, Maule Region, Chile
FALP ( Site 0301)Active Not Recruiting
Santiago, Region M. de Santiago, Chile
Pontificia Universidad Catolica de Chile ( Site 0303)Recruiting
Santiago, Region M. de Santiago, Chile
Bradfordhill ( Site 0300)Recruiting
Santiago, Region M. de Santiago, Chile
FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0406)Recruiting
Bogotá, Bogota D.C., Colombia
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402)Recruiting
Bogotá, Bogota D.C., Colombia
Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400)Recruiting
Valledupar, Cesar Department, Colombia
IMAT S.A.S ( Site 0404)Recruiting
Montería, Departamento de Córdoba, Colombia
Fundación Valle del Lili-Oncology CIC ( Site 0403)Recruiting
Cali, Valle del Cauca Department, Colombia
Herlev and Gentofte Hospital ( Site 0501)Recruiting
Copenhagen, Capital Region, Denmark
Aalborg Universitetshospital, Syd ( Site 0503)Recruiting
Aalborg, North Denmark, Denmark
Vaasan Keskussairaala ( Site 0603)Recruiting
Vaasa, Pohjanmaa, Finland
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) ( Site 0604)Recruiting
Helsinki, Uusimaa, Finland
Docrates Syöpäsairaala ( Site 0602)Recruiting
Helsinki, Uusimaa, Finland
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0703)Recruiting
Bordeaux, Aquitaine, France
Hopitaux Universitaires de Strasbourg ( Site 0700)Recruiting
Strasbourg, Bas-Rhin, France
Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702)Recruiting
Paris, France
Gustave Roussy ( Site 0701)Recruiting
Villejuif, Île-de-France Region, France
Universitaetsklinikum Heidelberg ( Site 0805)Recruiting
Heidelberg, Baden-Wurttemberg, Germany
Universitaetsklinikum Tuebingen-Urologie ( Site 0801)Recruiting
Tübingen, Baden-Wurttemberg, Germany
klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0802)Recruiting
Munich, Bavaria, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800)Active Not Recruiting
Berlin, Germany
Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804)Recruiting
Hamburg, Germany
St. Vincent's University Hospital ( Site 0901)Recruiting
Dublin, Dublin, Ireland
Cork University Hospital ( Site 0902)Recruiting
Cork, Ireland
Tallaght University Hospital ( Site 0900)Recruiting
Dublin, Ireland
Rambam Health Care Campus-Oncology Division ( Site 1002)Recruiting
Haifa, Israel
Rabin Medical Center ( Site 1001)Recruiting
Petah Tikva, Israel
Sheba Medical Center ( Site 1000)Recruiting
Ramat Gan, Israel
Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1102)Completed
Rome, Lazio, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1103)Recruiting
Milan, Lombardy, Italy
Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1101)Recruiting
Rozzano, Milano, Italy
Azienda Ospedaliera Universitaria Integrata Verona - Ospedal-Centro Ricerche Cliniche di Verona ( Site 1100)Recruiting
Verona, Italy
Toho University Sakura Medical Center ( Site 1201)Recruiting
Sakura, Chiba, Japan
Yokohama City University Medical Center ( Site 1203)Recruiting
Yokohama, Kanagawa, Japan
The Jikei University Hospital ( Site 1202)Completed
Mitato, Tokyo, Japan
Kyushu University Hospital ( Site 1204)Recruiting
Fukuoka, Japan
Auckland City Hospital ( Site 1333)Recruiting
Auckland, New Zealand
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1402)Recruiting
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 1400)Recruiting
Warsaw, Masovian Voivodeship, Poland
Uniwersyteckie Centrum Kliniczne ( Site 1405)Recruiting
Gdansk, Pomeranian Voivodeship, Poland
Asan Medical Center-Oncology ( Site 1500)Recruiting
Songpagu, Seoul, South Korea
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1502)Recruiting
Seoul, South Korea
Samsung Medical Center-Division of Hematology/Oncology ( Site 1501)Recruiting
Seoul, South Korea
Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 1603)Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1600)Recruiting
Madrid, Madrid, Comunidad de, Spain
Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1602)Recruiting
Barcelona, Spain
Hospital General Universitario Gregorio Marañón ( Site 1601)Recruiting
Madrid, Spain
Hospital Clinico San Carlos-Oncology Department ( Site 1604)Recruiting
Madrid, Spain
Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1704)Recruiting
Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
China Medical University Hospital ( Site 1703)Recruiting
Taichung, Taiwan
Taipei Veterans General Hospital ( Site 1701)Recruiting
Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch-Medical Oncology ( Site 1702)Recruiting
Taoyuan, Taiwan
Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1802)Recruiting
Adana, Turkey (Türkiye)
Hacettepe Universite Hastaneleri-oncology hospital ( Site 1800)Recruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Şehir Hastanesi ( Site 1801)Recruiting
Ankara, Turkey (Türkiye)
Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1804)Recruiting
Istanbul, Turkey (Türkiye)
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1803)Recruiting
Istanbul, Turkey (Türkiye)
Addenbrooke's Hospital ( Site 1902)Recruiting
Cambridge, Cambridgeshire, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 1904)Recruiting
Glasgow, Glasgow City, United Kingdom
Royal Preston Hospital-Lancashire Clinical Research Facility ( Site 1900)Recruiting
Preston, Lancashire, United Kingdom
University College London Hospital ( Site 1905)Recruiting
London, London, City of, United Kingdom
Queen Elizabeth Hospital Birmingham ( Site 1903)Recruiting
Birmingham, United Kingdom
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) · TrialPath