Prostatic Neoplasms, Castration-Resistant
Conditions
Brief 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.
Interventions
DRUGOpevesostat
Oral Tablet
DRUGOlaparib
Oral Tablet
DRUGDocetaxel
IV Infusion
DRUGCabazitaxel
IV Infusion
Oral Tablet
DRUGDexamethasone
Oral Tablet
DRUGPrednisone
Oral Tablet
Sponsors
Merck Sharp & Dohme LLC
Orion Corporation, Orion Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who experience one or more dose-limiting toxicities (DLTs) | Up to approximately 28 days | 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. |
| Number of participants who experience one or more adverse events (AEs) | Up to approximately 46 months | 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. |
| Number of participants who discontinue study intervention due to an AE | Up to approximately 46 months | 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. |
| Prostate-specific antigen (PSA) response rate | Up to approximately 46 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 46 months | 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). |
| Radiographic progression-free survival (rPFS) | Up to approximately 46 months | 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. |
| Overall survival (OS) | Up to approximately 46 months | OS is defined as the time from randomization to death due to any cause. |
| Duration of response (DOR) | Up to approximately 46 months | 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 to first subsequent anticancer therapy (TFST) | Up to approximately 46 months | TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first. |
| Time to pain progression (TTPP) | Up to approximately 46 months | 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. |
Countries
Australia, Canada, Chile, Colombia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, New Zealand, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed