A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer
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
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 is associated with response to therapy.
III. To evaluate the number and ETS fusion status of CTCs at baseline in all patients.
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
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Confirmed PSA response rate
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.
Up to 2 years
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Washington Medical Center||Seattle, Washington 98195-6043|
|City of Hope Medical Center||Duarte, California 91010|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|University of Chicago||Chicago, Illinois 60637|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|M D Anderson Cancer Center||Houston, Texas 77030|
|University of Southern California||Los Angeles, California 90033|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|
|UMDNJ - Robert Wood Johnson University Hospital||New Brunswick, New Jersey 08903|
|University of Wisconsin Cancer Center Riverview||Wisconsin Rapids, Wisconsin 54494|