Talazoparib Plus Enzalutamide After Progression to Abiraterone in Metastatic Prostate Cancer: (TEAM PC)
NCT Number: NCT06582628
Acronym: TEAM PC
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Metastatic Prostate Cancer
Interventions: DRUG: Enzalutamide capsule|DRUG: Enzalutamide capsule and Talazoparib capsule
Sponsor: Fundacion Oncosur
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 78
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-05
Completion Date: 2027-10-31
Locations: Hospital 12 de Octubre, Madrid, 28041, Spain

Summary:
The purpose of this clinical trial is to determine the anti-tumor activity of talazoparib plus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed on abiraterone.

The main questions it aims to answer are:

* Does talazoparib plus enzalutamide improve efficacy in metastatic castration resistant prostate cancer (mCRPC) compared to enzalutamide alone?
* What is the time to disease progression \[radiographic, Prostate Specific Antigen (PSA), clinical\] in participants treated with talazoparib plus enzalutamide after progression on abiraterone?
* What medical problems do participants have when receiving talazoparib plus enzalutamide?

Researchers will compare the combination of talazoparib and enzalutamide as a first-line treatment for mCRPC to see if the combination improves the PSA response rate and delays progression compared to enzalutamide alone. The safety and tolerability of the combination (talazoparib and enzalutamide) will also be studied

Primary Outcome Measures: PSA response (PSA50), Percentage of participants with a PSA decline greater than or equal to 50 percent from baseline confirmed by a consecutive PSA value (taken at least 3 weeks apart), prior to PSA progression, within the first 16 weeks|Objective response rate (ORR), Defined as the best overall radiographic response (partial or complete) during the first 16 weeks on follow up as per investigator assessment of soft tissue/visceral disease per RECIST 1.1 in subjects who have a measurable tumour and/or Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases, during the first 16 weeks
Secondary Outcome Measures: Radiographic Progression Free Survival (rPFS), Time from randomization to first objective evidence of radiographic progression, based on RECIST 1.1 for soft tissue/visceral disease and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines for bone metastases, or death, whichever occurs first., Through study completion, an average of 2 years|Time to PSA Progression (TTPP), Time from randomization to PSA progression defined as PSA greater than or equal to 25 percent and greater than or equal to 2ng/mL from nadir (or baseline for participants with no PSA decline), confirmed by a second value obtained 3 or more weeks apart as per PCWG3 guidelines., Through study completion, an average of 2 years|Time to unequivocal clinical progression (TTCP), Time from randomization to clinical worsening of prostate cancer related symptoms, as new onset cancer pain requiring chronic administration of opiate analgesia, deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to 3 or higher, time to first skeletal-related event (the time from randomization to first incidence of radiotherapy to the bone or bone surgery, pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain); or initiation of subsequent lines of active treatment including cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications or symptoms related to disease progression., Through study completion, an average of 2 years|Progression Free Survival (PFS), Time from randomization to PSA progression, unequivocal clinical progression or radiographic progression, whichever occurs first., Through study completion, an average of 2 years|Incidence of adverse events (AEs), Total, grouped by grades and AEs category, related and unrelated with the trial treatment. The AEs Defined as incidence of prespecified AEs as per National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, change from baseline in targeted vital signs and change from baseline in targeted clinical laboratory test results., Through study completion, an average of 2 years|Incidence of serious adverse events (SAEs), Number of Serious Adverse Events, related and unrelated. SAEs leading to treatment discontinuation., Through study completion, an average of 2 years|Drug compliance, Percentage of dose taken for each treatment drug, dose reductions, dose discontinuation (temporary or permanent), Through study completion, an average of 2 years
Other Outcome Measures: Assessment of PSA response rate, In participants with and without germline and/or somatic DDR alterations., Through study completion, an average of 2 years|Assessment of ORR, In participants with and without germline and/or somatic DDR alterations, Through study completion, an average of 2 years|Assessment of rPFS, In participants with and without germline and/or somatic DDR alterations, Through study completion, an average of 2 years|Assessment of TTPP, In participants with and without germline and/or somatic DDR alterations., Through study completion, an average of 2 years|Assessment of TTCP, In participants with and without germline and/or somatic DDR alterations., Through study completion, an average of 2 years|Changes in expression levels of AR in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Changes in expression levels of AR in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Changes in expression of AR-related genes in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Changes in expression of AR-related genes in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Changes in open chromatin regions in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Changes in open chromatin regions in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Survival signaling in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Survival signaling in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|DNA-damage in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|DNA-damage in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Deficient/proficient DNA-repair in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Deficient/proficient DNA-repair in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Other biomarkers in tissue, Changes from tissue samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years|Other biomarkers in plasma, Changes from plasma samples, studying the correlation of these changes with clinical activity, Through study completion, an average of 2 years