This randomized phase II trial studies abiraterone acetate and prednisone together with veliparib to see how well it works compared to abiraterone acetate and prednisone alone in treating patients with castration-resistant prostate cancer that has spread from the primary site to other places in the body. Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abiraterone acetate together with prednisone and veliparib may work better than abiraterone acetate and prednisone alone in treating patients with castration-resistant prostate cancer.
PRIMARY OBJECTIVES: I. To evaluate the role of v-ets erythroblastosis virus E26 oncogene (ETS) gene fusion as a predictive biomarker for response to hormone therapy (abiraterone \[abiraterone acetate\]) alone or hormone therapy plus poly adenosine diphosphate-ribose polymerase 1 (PARP-1) targeted therapy (ABT-888 \[veliparib\]) in patients with metastatic castration resistant prostate cancer. II. To evaluate whether the addition of PARP-1 targeted therapy is superior to hormone therapy alone based on ETS gene fusion status. SECONDARY OBJECTIVES: I. Rate of prostate-specific antigen (PSA) declines. II. Objective response rate. III. Progression-free survival. IV. Evaluate the qualitative and quantitative toxicity of abiraterone acetate with and without ABT-888. TERTIARY OBJECTIVES: I. To determine the concordance in fusion status among prostate cancer samples from the primary site, biopsied metastasis, and circulating tumor cells (CTCs). II. To assess if ETS fusion status in the CTCs, at baseline, 12 weeks, and disease progression (or when off study) is associated with response to therapy. III. To evaluate if the number of CTCs, as well as the expression levels of androgen receptor, RAD51 recombinase (RAD51), and gamma-H2A histone family, member X (H2aX) foci in the CTCs at baseline, at 12 weeks, and at disease progression in all patients is associated with response to therapy. IV. To determine the role of phosphatase and tensin homolog (PTEN) loss as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888. V. To determine the role of PARP1 activity as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888. VI. To perform next-generation sequencing for discovery of novel gene fusions in prostate cancers negative for ETS fusions. VII. To perform germline single nucleotide polymorphism (SNP) analysis of genes involved in hormone synthesis, transport, binding, metabolism, and degradation for discovery of novel SNPs predictive of response to abiraterone, alone or in combination with ABT-888. VIII. To determine if ETS fusion ribonucleic acid (RNA) levels in blood are predictive of response to abiraterone, alone or in combination with ABT-888. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive abiraterone acetate orally (PO) once daily (QD) and prednisone PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
159
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
...and 4 more locations
Confirmed Prostate-specific Antigen (PSA) Response Rate
50% or greater decline in PSA from baseline.
Time frame: Up to 3 years
Rates of PSA Decline
Change in PSA from baseline to 12 weeks
Time frame: 12 weeks
Objective Response Rates in Patients With Measurable Disease.
Overall response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 3 years
Progression-free Survival (PFS)
Time from randomization to disease progression or death.
Time frame: Up to 42 months
Grade 4 or 5 Adverse Events
Grade 4 or greater toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 at least possibly related to treatment.
Time frame: 30 days after completion of study treatment
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