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)
Recruiting · NCT06353386 · Interventional (participants receive a specific treatment) · Lead sponsor: Merck Sharp & Dohme LLC
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Age range
18 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
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.
Where it is running
60 locations listed across 6 US states.
- UCSD Moores Cancer Center ( Site 0039) - La Jolla, California, United States
- UCLA Hematology/Oncology - Santa Monica ( Site 0044) - Los Angeles, California, United States
- University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051) - Miami, Florida, United States
- University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049) - Baltimore, Maryland, United States
- Rutgers Cancer Institute of New Jersey ( Site 0033) - New Brunswick, New Jersey, United States
- University Hospitals Cleveland Medical Center ( Site 0043) - Cleveland, Ohio, United States
- MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020) - Milwaukee, Wisconsin, United States
- Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1802) - Adana, Turkey (Türkiye)
- Hacettepe Universite Hastaneleri-oncology hospital ( Site 1800) - Ankara, Turkey (Türkiye)
- Ankara Bilkent Şehir Hastanesi ( Site 1801) - Ankara, Turkey (Türkiye)
- Auckland City Hospital ( Site 1333) - Auckland, New Zealand
- Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1602) - Barcelona, Spain
- Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800) - Berlin, Germany
- Queen Elizabeth Hospital Birmingham ( Site 1903) - Birmingham, United Kingdom
- Cork University Hospital ( Site 0902) - Cork, Ireland
- Tallaght University Hospital ( Site 0900) - Dublin, Ireland
- Kyushu University Hospital ( Site 1204) - Fukuoka, Japan
- Rambam Health Care Campus-Oncology Division ( Site 1002) - Haifa, Israel
- Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804) - Hamburg, Germany
- Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1804) - Istanbul, Turkey (Türkiye)
- TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1803) - Istanbul, Turkey (Türkiye)
- Hospital General Universitario Gregorio Marañón ( Site 1601) - Madrid, Spain
- Hospital Clinico San Carlos-Oncology Department ( Site 1604) - Madrid, Spain
- Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702) - Paris, France
- Rabin Medical Center ( Site 1001) - Petah Tikva, Israel
- Sheba Medical Center ( Site 1000) - Ramat Gan, Israel
- Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1502) - Seoul, South Korea
- Samsung Medical Center-Division of Hematology/Oncology ( Site 1501) - Seoul, South Korea
- China Medical University Hospital ( Site 1703) - Taichung, Taiwan
- Taipei Veterans General Hospital ( Site 1701) - Taipei, Taiwan
- Chang Gung Medical Foundation-Linkou Branch-Medical Oncology ( Site 1702) - Taoyuan, Taiwan
- Azienda Ospedaliera Universitaria Integrata Verona - Ospedal-Centro Ricerche Cliniche di Verona ( Site 1100) - Verona, Italy
- Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0703) - Bordeaux, Aquitaine, France
- Universitaetsklinikum Heidelberg ( Site 0805) - Heidelberg, Baden-Wurttemberg, Germany
- Universitaetsklinikum Tuebingen-Urologie ( Site 0801) - Tübingen, Baden-Wurttemberg, Germany
- Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 1603) - L'Hospitalet de Llobregat, Barcelona, Spain
- Hopitaux Universitaires de Strasbourg ( Site 0700) - Strasbourg, Bas-Rhin, France
- klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0802) - Munich, Bavaria, Germany
- CIDO SpA-Oncology ( Site 0302) - Temuco, Biobio, Chile
- FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0406) - Bogotá, Bogota D.C., Colombia
- Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402) - Bogotá, Bogota D.C., Colombia
- Addenbrooke's Hospital ( Site 1902) - Cambridge, Cambridgeshire, United Kingdom
- Herlev and Gentofte Hospital ( Site 0501) - Copenhagen, Capital Region, Denmark
- Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400) - Valledupar, Cesar Department, Colombia
- Toho University Sakura Medical Center ( Site 1201) - Sakura, Chiba, Japan
- IMAT S.A.S ( Site 0404) - Montería, Departamento de Córdoba, Colombia
- St. Vincent's University Hospital ( Site 0901) - Dublin, Dublin, Ireland
- The Beatson West of Scotland Cancer Centre ( Site 1904) - Glasgow, Glasgow City, United Kingdom
- Yokohama City University Medical Center ( Site 1203) - Yokohama, Kanagawa, Japan
- Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1704) - Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1402) - Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
- Royal Preston Hospital-Lancashire Clinical Research Facility ( Site 1900) - Preston, Lancashire, United Kingdom
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1102) - Rome, Lazio, Italy
- Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1103) - Milan, Lombardy, Italy
- University College London Hospital ( Site 1905) - London, London, City of, United Kingdom
- Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1600) - Madrid, Madrid, Comunidad de, Spain
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 1400) - Warsaw, Masovian Voivodeship, Poland
- Clinica Universidad Catolica del Maule-Oncology ( Site 0304) - Talca, Maule Region, Chile
- Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1101) - Rozzano, Milano, Italy
- Macquarie University-MQ Health Clinical Trials Unit ( Site 0108) - Macquarie University, New South Wales, Australia
Showing 60 of 77 listed sites. See the official record for the complete list.
Read the full protocol, contacts and eligibility on ClinicalTrials.gov →