Phase II Trial of Single Agent ABT-888 With Post-Progression Therapy of ABT-888 in Combination With Carboplatin in Patients With Stage IV BRCA-Associated Breast Cancer
I. To evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in BRCA
carriers with metastatic breast cancer based on response rate (RECIST criteria).
I. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. II. To
evaluate progression-free survival of patients on single-agent ABT-888. III. To further
describe the safety and tolerability of ABT-888 (NSC 737664) as a single agent and in
combination with carboplatin for BRCA-associated breast cancer.
IV. To evaluate the pharmacokinetics of ABT-888 (NSC 737664) alone and in combination with
V. To assess the relationship between the level of PARP inhibition by ABT-888 and biomarkers
of DNA damage in PBMC's and in tumor VI. To explore the relationship between biomarkers of
drug effect and progression-free survival.
VII. To evaluate the efficacy and safety of the combination of carboplatin and ABT-888 in
patients who have failed single agent ABT-888.
VIII. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0-1 vs 2), and hormone status (estrogen receptor [ER]- and/or progesterone receptor
[PR]-positive vs ER- and/or PR-negative). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral veliparib twice daily on days 1-21.
ARM II: Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in arm I.
In both arms, treatment repeats every 21 days in the absence of disease progression or
unacceptable toxicity. Patients undergo blood and hair follicle sample collection for
pharmacokinetics and other laboratory studies.
After completion of study therapy, patients are followed up every 3-6 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate as measured by RECIST version 1.1
Up to 4 years
Beckman Research Institute
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Mayo Clinic||Rochester, Minnesota 55905|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Weill Medical College of Cornell University||New York, New York 10021|
|University of Colorado||Denver, Colorado 80217|
|City of Hope Medical Center||Duarte, California 91010|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|M D Anderson Cancer Center||Houston, Texas 77030|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Magee-Womens Hospital - University of Pittsburgh Medical Center||Pittsburgh, Pennsylvania 15213|