Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
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 metastatic hormone-resistant prostate cancer. 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. It is not yet known whether giving abiraterone acetate together with prednisone and veliparib is more effective than abiraterone acetate and prednisone alone in treating prostate cancer.
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: abiraterone acetate
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer|
- Confirmed PSA response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The corresponding binomial confidence intervals will be reported for each arm. A logistic model including treatment group, fusion status, and prior ketoconazole use will be used to determine the interaction between the rates of PSA response between abiraterone and abiraterone + ABT-888 and ETS fusion status.
- Rates of PSA decline [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Will be exhibited using waterfall plots of 12 week PSA decline and maximum PSA decline by treatment arm. Additionally, the rate of PSA decline will be explored using a repeated measures mixed model with the natural log of PSA as the outcome.
- Objective response rates [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Will be reported by treatment with corresponding binomial confidence intervals.
- Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ] [ Designated as safety issue: No ]Kaplan-Meier methods will be used to describe progression free survival by arm.
- Grade 4 or greater toxicity of abiraterone acetate and abiraterone acetate + veliparib [ Time Frame: 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Will be described by type, grade, and frequency for each treatment and arm.
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Arm I (abiraterone acetate and prednisone)
Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: abiraterone acetate
Other Names:Drug: prednisone
Other Names:Other: laboratory biomarker analysis
Experimental: Arm II (abiraterone acetate, prednisone, and veliparib)
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.
Drug: abiraterone acetate
Other Names:Drug: prednisone
Other Names:Drug: veliparib
Other Name: ABT-888Other: laboratory biomarker analysis
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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.
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.
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, and gamma-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.
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Przemyslaw W. Twardowski 626-256-4673 firstname.lastname@example.org|
|Principal Investigator: Przemyslaw W. Twardowski|
|University of Southern California||Recruiting|
|Los Angeles, California, United States, 90033-0804|
|Contact: David I. Quinn 323-865-3956 email@example.com|
|Principal Investigator: David I. Quinn|
|City of Hope Medical Group Inc||Recruiting|
|Pasadena, California, United States, 91105|
|Contact: Stephen C. Koehler 626-396-2900 firstname.lastname@example.org|
|Principal Investigator: Stephen C. Koehler|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Maha H. Hussain 734-936-8906 email@example.com|
|Principal Investigator: Maha H. Hussain|
|Evanston CCOP-NorthShore University HealthSystem||Recruiting|
|Evanston, Illinois, United States, 60201|
|Contact: Daniel H. Shevrin 847-570-2515 DShevrin@northshore.org|
|Principal Investigator: Daniel H. Shevrin|
|United States, Indiana|
|Indiana University Medical Center||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Noah M. Hahn 317-948-1186 firstname.lastname@example.org|
|Principal Investigator: Noah M. Hahn|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287-8936|
|Contact: Emmanuel S. Antonarakis 410-502-7528 email@example.com|
|Principal Investigator: Emmanuel S. Antonarakis|
|United States, Michigan|
|University of Michigan University Hospital||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Felix Y. Feng 734-936-4302 firstname.lastname@example.org|
|Principal Investigator: Felix Y. Feng|
|United States, New Jersey|
|UMDNJ - Robert Wood Johnson University Hospital||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Mark N. Stein 732-235-3336 email@example.com|
|Principal Investigator: Mark N. Stein|
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Young E. Whang 919-843-9983 firstname.lastname@example.org|
|Principal Investigator: Young E. Whang|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Paul G. Corn 713-792-2830 email@example.com|
|Principal Investigator: Paul G. Corn|
|United States, Washington|
|University of Washington Medical Center||Recruiting|
|Seattle, Washington, United States, 98195|
|Contact: Robert B. Montgomery 206-598-0860 firstname.lastname@example.org|
|Principal Investigator: Robert B. Montgomery|
|United States, Wisconsin|
|University of Wisconsin Cancer Center Riverview||Recruiting|
|Wisconsin Rapids, Wisconsin, United States, 54494|
|Contact: Glenn Liu 608-265-8689 email@example.com|
|Principal Investigator: Glenn Liu|
|Principal Investigator:||Maha Hussain||University of Chicago Comprehensive Cancer Center|