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.
PRIMARY OBJECTIVES: I. Increase the efficacy of first-line therapy for men with metastatic castration-sensitive prostate cancer by adding the PARP inhibitor talazoparib to standard therapy with androgen deprivation therapy (ADT) + abiraterone acetate (abiraterone). II. Study the efficacy of abiraterone and talazoparib in an ethnically diverse population. III. Evaluate whether androgen receptor genetic variation may identify a subpopulation of patients who benefit, even in the absence of homologous repair deficiency mutations. OUTLINE: Patients receive talazoparib orally (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD on days 1-28. Patients also receive androgen deprivation therapy consisting of degarelix subcutaneously (SC) on day 1; leuprolide acetate intramuscularly (IM) on day 1 and bicalutamide PO QD on days 1-28 of cycle 1 and then leuprolide acetate IM on day 1 of subsequent cycles; leuprolide acetate IM on day 1 and bicalutamide PO QD on days 1-28 of cycle 1 and then leuprolide acetate IM on day 1 of cycles 2, 5, 8, and 11; or goserelin acetate SC monthly or every 3 months. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Given PO
Given PO
Given SC
Given SC
Given IM
Given PO
Ancillary studies
Given PO
City of Hope Medical Center
Duarte, California, United States
RECRUITINGProstate specific antigen (PSA) nadir < 0.2
Will be estimated with 95% Clopper-Pearson interval.
Time frame: At 12 months
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.
Time frame: Up to 2 years
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.
Time frame: Up to 2 years
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.
Time frame: Up to 2 years
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.
Time frame: Up to 2 years
Androgen receptor (AR) genetic variations
The effect of AR genetic variations on PSA nadir \<0.2 at 12 months, ORR, PSA response or PFS. AR CAG and GGC repeats will be analyzed as a continuous variable as well dichotomized as high versus low. PSA nadir results will be compared between CAG/GGC repeat groups.
Time frame: Up to 2 years
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