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)
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.
Arms & interventions
- DrugOpevesostat
Oral Tablet
- DrugOlaparib
Oral Tablet
- DrugDocetaxel
IV Infusion
- DrugCabazitaxel
IV Infusion
- DrugFludrocortisone acetate
Oral Tablet
- DrugDexamethasone
Oral Tablet
- DrugPrednisone
Oral Tablet
Outcome measures
Primary
Number of participants who experience one or more dose-limiting toxicities (DLTs)
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.
Time frame: Up to approximately 28 days
Number of participants who experience one or more adverse events (AEs)
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.
Time frame: Up to approximately 46 months
Number of participants who discontinue study intervention due to an AE
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.
Time frame: Up to approximately 46 months
Prostate-specific antigen (PSA) response rate
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.
Time frame: Up to approximately 46 months
Secondary
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
Study locations (7)
UCSD Moores Cancer Center ( Site 0039)
La Jolla, California, 92037
UCLA Hematology/Oncology - Santa Monica ( Site 0044)
Los Angeles, California, 90404
University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)
Miami, Florida, 33136
University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049)
Baltimore, Maryland, 21201
Rutgers Cancer Institute of New Jersey ( Site 0033)
New Brunswick, New Jersey, 08903-2681
University Hospitals Cleveland Medical Center ( Site 0043)
Cleveland, Ohio, 44106
MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)
Milwaukee, Wisconsin, 53226