Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
|ClinicalTrials.gov Identifier: NCT01576172|
Recruitment Status : Active, not recruiting
First Posted : April 12, 2012
Last Update Posted : April 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma PSA Progression Recurrent Prostate Carcinoma Stage IV Prostate Cancer AJCC v7||Drug: Abiraterone Acetate Other: Laboratory Biomarker Analysis Drug: Prednisone Drug: Veliparib||Phase 2|
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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 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 (Clinical Trial)|
|Estimated Enrollment :||148 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 30, 2012|
|Estimated Primary Completion Date :||December 31, 2018|
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: 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: Laboratory Biomarker Analysis
- Confirmed PSA response rate [ Time Frame: Up to 2 years ]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 ]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 ]Will be reported by treatment with corresponding binomial confidence intervals.
- Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ]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 5.0 [ Time Frame: 30 days after completion of study treatment ]Will be described by type, grade, and frequency for each treatment and arm.
- Circulating T cells (CTC) enumeration [ Time Frame: Baseline ]CTCs at baseline will be described by treatment arm and strata.
- ETS fusion status [ Time Frame: Baseline ]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 ]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 ]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.
- Single nucleotide polymorphism (SNP) identification [ Time Frame: Baseline ]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 messenger ribonucleic acid (mRNA) levels [ Time Frame: Baseline to up to 2 years ]Logistic and Cox regression models may be used to explore baseline ribonucleic acid (RNA) levels or early changes in RNA levels to predict response and PFS respectively.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01576172
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|NorthShore University HealthSystem-Evanston Hospital|
|Evanston, Illinois, United States, 60201|
|United States, Indiana|
|Indiana University/Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Washington|
|University of Washington Medical Center|
|Seattle, Washington, United States, 98195|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Maha Hussain||University of Chicago Comprehensive Cancer Center|