This phase II trial studies the effect of talazoparib with androgen deprivation therapy and abiraterone in treating castration sensitive prostate cancer patients. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Androgen can cause the growth of prostate tumor cells. Degarelix, leuprolide acetate, bicalutamide, goserelin acetate, and abiraterone lowers the amount of androgen made by the body. This may help stop the growth of tumor cells that need androgen to grow. Giving talazoparib with androgen deprivation therapy and abiraterone may improve cancer control for patients with castration sensitive prostate cancer.
All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. (Note: Gleason score not required if biopsy of metastasis was used to make the histologic diagnosis)
All patients must have metastatic disease: either soft tissue and/or bony metastases prior to initiation of androgen. Measurable disease is not required
Baseline imaging must have been performed within 42 days before or 14 days after initiating luteinizing hormone releasing hormones (LHRH) therapy. All disease must be assessed and documented on the Baseline Tumor Assessment Form
Patients may have started on LHRH therapy for metastatic prostate cancer provided this was initiated no longer than 60 days prior to registration
Patients must not have received prior and/or must not have any plans for receiving concomitant therapy with ketoconazole, aminoglutethimide, or enzalutamide (MDV3100). Concurrent megestrol for hot flashes is allowed
Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer
Prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting may be allowed at the discretion of the principal investigator. At least 2 years must have elapsed since completion of cytotoxic chemotherapy in the neoadjuvant and/or adjuvant setting
Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. But, if brain imaging studies are performed, they must be negative for disease
Single group
Abiraterone Acetate
DrugGiven PO
Bicalutamide
DrugGiven PO
Degarelix
DrugGiven SC
Goserelin Acetate
DrugGiven SC
Leuprolide Acetate
DrugGiven IM
Prednisone
DrugGiven PO
Questionnaire Administration
Other interventionAncillary studies
Talazoparib
DrugGiven PO
Prostate specific antigen (PSA) nadir < 0.2
Will be estimated with 95% Clopper-Pearson interval.
Objective response rate
Will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for patients with measurable disease only, and summarized by % of patients achieving complete response, partial response, stable disease, or progressive disease as best response.
PSA responses
Will be described by waterfall plots as recommended by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as well as identifying the % of patients achieving a 50% and 90% reduction in PSA.
Radiographic progression-free survival (PFS)
Will be evaluated for all patients, using RECIST for soft tissue and including the PCWG3 criteria for bone scan assessment of progression of disease. PFS will be carried out by Kaplan-Meier curve and log-rank test will be used to detect difference between groups.
Patient reported outcomes
Will be collected using Functional Assessment of Cancer Therapy- Prostate and evaluated for changes from baseline, endpoint will be time to deterioration in quality of life.
Circulating tumor deoxyribonucleic acid (ctDNA)
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
