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 graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ 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.
- CTC enumeration [ Time Frame: Baseline ] [ Designated as safety issue: No ]CTCs at baseline will be described by treatment arm and strata.
- ETS fusion status [ Time Frame: Baseline ] [ Designated as safety issue: No ]Concordance of the ETS fusion status between samples (primary, metastatic, and CTCs) from each patient will be described and tested between the three populations using a generalized kappa. The three pairwise comparisons will also be investigated and McNemar's test and kappa statistic for each will be reported.
- PTEN expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]Logistic models with response as the outcome and loss of PTEN in the specimen will be used to determine if PTEN loss predict response to Abiraterone +/- ABT-888.
- PARP activity [ Time Frame: Baseline ] [ Designated as safety issue: No ]Logistic models with response as the outcome and expression levels of PAR in the specimen will be used to determine if PARP activity predict response to Abiraterone +/- ABT-888.
- SNP identification [ Time Frame: Baseline ] [ Designated as safety issue: No ]Standard quality control statistical analyses (i.e. Hardy-Weinberg Equilibrium testing) will be performed to analyze SNP assay results. Univariable analyses will be performed to identify candidate SNPs associated with favorable abiraterone outcomes.
- Change in ERG mRNA levels [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]Logistic and Cox regression models may be used to explore baseline RNA levels or early changes in RNA levels to predict response and PFS respectively.
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||June 2015 (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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|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/Norris Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|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: Walter M. Stadler 773-702-4150 email@example.com|
|Principal Investigator: Walter M. Stadler|
|NorthShore University HealthSystem-Evanston Hospital||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: Costantine Albany 317-948-8310 firstname.lastname@example.org|
|Principal Investigator: Costantine Albany|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21231|
|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: Maha H. Hussain 734-936-8906 firstname.lastname@example.org|
|Principal Investigator: Maha H. Hussain|
|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|