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)

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)

Overview

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.

Interventions

• Drug Opevesostat
  Oral Tablet
• Drug Olaparib
  Oral Tablet
• Drug Docetaxel
  IV Infusion
• Drug Cabazitaxel
  IV Infusion
• Drug Fludrocortisone acetate
  Oral Tablet
• Drug Dexamethasone
  Oral Tablet
• Drug Prednisone
  Oral Tablet

Primary outcome measures

• Number of participants who experience one or more dose-limiting toxicities (DLTs) [Time frame: Up to approximately 28 days]
• Number of participants who experience one or more adverse events (AEs) [Time frame: Up to approximately 46 months]
• Number of participants who discontinue study intervention due to an AE [Time frame: Up to approximately 46 months]
• Prostate-specific antigen (PSA) response rate [Time frame: Up to approximately 46 months]

Secondary outcome measures (6)

• Objective response rate (ORR) [Time frame: Up to approximately 46 months]
• Radiographic progression-free survival (rPFS) [Time frame: Up to approximately 46 months]
• Overall survival (OS) [Time frame: Up to approximately 46 months]
• Duration of response (DOR) [Time frame: Up to approximately 46 months]
• Time to first subsequent anticancer therapy (TFST) [Time frame: Up to approximately 46 months]
• Time to pain progression (TTPP) [Time frame: Up to approximately 46 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• UCSD Moores Cancer Center ( Site 0039) — La Jolla
• UCLA Hematology/Oncology - Santa Monica ( Site 0044) — Los Angeles
• University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services — Miami
• University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049) — Baltimore
• Rutgers Cancer Institute of New Jersey ( Site 0033) — New Brunswick
• University Hospitals Cleveland Medical Center ( Site 0043) — Cleveland
• MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020) — Milwaukee

Chile · 5 centers

• CIDO SpA-Oncology ( Site 0302) — Temuco
• Clinica Universidad Catolica del Maule-Oncology ( Site 0304) — Talca
• FALP ( Site 0301) — Santiago
• Pontificia Universidad Catolica de Chile ( Site 0303) — Santiago
• Bradfordhill ( Site 0300) — Santiago

Colombia · 5 centers

• FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO AN — Bogotá
• Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402) — Bogotá
• Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400) — Valledupar
• IMAT S.A.S ( Site 0404) — Montería
• Fundación Valle del Lili-Oncology CIC ( Site 0403) — Cali

Germany · 5 centers

• Universitaetsklinikum Heidelberg ( Site 0805) — Heidelberg
• Universitaetsklinikum Tuebingen-Urologie ( Site 0801) — Tübingen
• klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Polikl — Munich
• Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800) — Berlin
• Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804) — Hamburg

Spain · 5 centers

• Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 1603) — L'Hospitalet de Llobregat
• Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1600) — Madrid
• Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1602) — Barcelona
• Hospital General Universitario Gregorio Marañón ( Site 1601) — Madrid
• Hospital Clinico San Carlos-Oncology Department ( Site 1604) — Madrid

Turkey (Türkiye) · 5 centers

• Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1802) — Adana
• Hacettepe Universite Hastaneleri-oncology hospital ( Site 1800) — Ankara
• Ankara Bilkent Şehir Hastanesi ( Site 1801) — Ankara
• Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1804) — Istanbul
• TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1803 — Istanbul

United Kingdom · 5 centers

• Addenbrooke's Hospital ( Site 1902) — Cambridge
• The Beatson West of Scotland Cancer Centre ( Site 1904) — Glasgow
• Royal Preston Hospital-Lancashire Clinical Research Facility ( Site 1900) — Preston
• University College London Hospital ( Site 1905) — London
• Queen Elizabeth Hospital Birmingham ( Site 1903) — Birmingham

France · 4 centers

• Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( S — Bordeaux
• Hopitaux Universitaires de Strasbourg ( Site 0700) — Strasbourg
• Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702) — Paris
• Gustave Roussy ( Site 0701) — Villejuif

Italy · 4 centers

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1102) — Rome
• Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Si — Milan
• Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1101) — Rozzano
• Azienda Ospedaliera Universitaria Integrata Verona - Ospedal-Centro Ricerche Cliniche di V — Verona

Japan · 4 centers

• Toho University Sakura Medical Center ( Site 1201) — Sakura
• Yokohama City University Medical Center ( Site 1203) — Yokohama
• The Jikei University Hospital ( Site 1202) — Mitato
• Kyushu University Hospital ( Site 1204) — Fukuoka

Taiwan · 4 centers

• Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1704) — Kaohsiung Niao Sung Dist
• China Medical University Hospital ( Site 1703) — Taichung
• Taipei Veterans General Hospital ( Site 1701) — Taipei
• Chang Gung Medical Foundation-Linkou Branch-Medical Oncology ( Site 1702) — Taoyuan

Australia · 3 centers

• Macquarie University-MQ Health Clinical Trials Unit ( Site 0108) — Macquarie University
• Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107) — Greenslopes
• Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110) — Melbourne

Canada · 3 centers

• Centre Hospitalier de l'Université de Montréal ( Site 0200) — Montreal
• Jewish General Hospital ( Site 0206) — Montreal
• Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésu — Québec

Finland · 3 centers

• Vaasan Keskussairaala ( Site 0603) — Vaasa
• Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) ( Site 060 — Helsinki
• Docrates Syöpäsairaala ( Site 0602) — Helsinki

Ireland · 3 centers

• St. Vincent's University Hospital ( Site 0901) — Dublin
• Cork University Hospital ( Site 0902) — Cork
• Tallaght University Hospital ( Site 0900) — Dublin

Israel · 3 centers

• Rambam Health Care Campus-Oncology Division ( Site 1002) — Haifa
• Rabin Medical Center ( Site 1001) — Petah Tikva
• Sheba Medical Center ( Site 1000) — Ramat Gan

Poland · 3 centers

• Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1402) — Bydgoszcz
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( — Warsaw
• Uniwersyteckie Centrum Kliniczne ( Site 1405) — Gdansk

South Korea · 3 centers

• Asan Medical Center-Oncology ( Site 1500) — Songpagu
• Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1502) — Seoul
• Samsung Medical Center-Division of Hematology/Oncology ( Site 1501) — Seoul

Denmark · 2 centers

• Herlev and Gentofte Hospital ( Site 0501) — Copenhagen
• Aalborg Universitetshospital, Syd ( Site 0503) — Aalborg

New Zealand · 1 center

• Auckland City Hospital ( Site 1333) — Auckland

Identifiers

NCT: NCT06353386 · 5684-01A · MK-5684-01A · 2023-506288-33-00 · U1111-1292-6912 · jRCT2031240224

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗