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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Oral Tablet
Oral Tablet
IV Infusion
IV Infusion
Oral Tablet
Oral Tablet
Oral Tablet
UCSD Moores Cancer Center ( Site 0039)
La Jolla, California, United States
RECRUITINGUCLA Hematology/Oncology - Santa Monica ( Site 0044)
Los Angeles, California, United States
RECRUITINGUniversity of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)
Miami, Florida, United States
RECRUITINGUniversity of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049)
Baltimore, Maryland, United States
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
Objective response rate (ORR)
The ORR is defined as the percentage of participants with complete response (CR: disappearance of all target lesions per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); and no evidence of disease (NED) on base scan per Prostate Cancer Working Group (PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). ORR will be assessed by Blinded Independent Central Review (BICR).
Time frame: Up to approximately 46 months
Radiographic progression-free survival (rPFS)
rPFS is defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 is ≥20% increase in the sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria is the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for ≥6 weeks. rPFS will be assessed by BICR.
Time frame: Up to approximately 46 months
Overall survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 46 months
Duration of response (DOR)
DOR is defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a least 5 mm. PD per PCWG is the appearance of \>2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for \>6 weeks. DOR will be assessed by BICR.
Time frame: Up to approximately 46 months
Time to first subsequent anticancer therapy (TFST)
TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.
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Rutgers Cancer Institute of New Jersey ( Site 0033)
New Brunswick, New Jersey, United States
ACTIVE_NOT_RECRUITINGUniversity Hospitals Cleveland Medical Center ( Site 0043)
Cleveland, Ohio, United States
RECRUITINGMEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)
Milwaukee, Wisconsin, United States
RECRUITINGMacquarie University-MQ Health Clinical Trials Unit ( Site 0108)
Macquarie University, New South Wales, Australia
RECRUITINGGallipoli Medical Research Ltd-GMRF CTU ( Site 0107)
Greenslopes, Queensland, Australia
RECRUITINGPeter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110)
Melbourne, Victoria, Australia
RECRUITING...and 67 more locations
Time frame: Up to approximately 46 months
Time to pain progression (TTPP)
TTPP is defined as the time from randomization to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and by opiate analgesic use.
Time frame: Up to approximately 46 months