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
18 Years
N/A
Female
BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
Trial Information
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
PRIMARY OBJECTIVES:
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).
SECONDARY OBJECTIVES:
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
carboplatin.
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.
Inclusion Criteria:
- Histologically confirmed breast cancer
- Metastatic or locally advanced disease
- Disease not amenable to surgery
- Standard curative measures do not exist or are no longer effective
- Patient must have a known deleterious BRCA mutation confirmed by report from a CLIA
certified laboratory
- Measurable disease by RECIST criteria
- At least 3 weeks since prior chemotherapy
- Hormone receptor status known
- ECOG performance status 0-2
- Life expectancy > 4 months
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if there is evidence of liver metastasis)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Negative pregnancy test
- Fertile patients must agree to use effective contraception before, during, and for 3
months after completion of study therapy
- Ability to understand and the willingness to sign a written informed consent document
- No prior therapy with platinum agents or PARP inhibitors
- Prior adjuvant platinum agents within the past 12 months allowed
- No other concurrent investigational agents
- No known CNS metastases with active symptomatology, or requiring anticonvulsant
medications or steroids
- Patients on anticonvulsant medications prescribed for reasons other than CNS
metastases, not on steroids and without active symptomatology allowed
- Patients with active seizure or a history of seizure; patients with CNS metastases
must be stable after therapy for > 3 months and off steroid treatment prior to study
enrollment
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to veliparib or PARP Inhibitors
- No contraindications to platinum agents
- More than 5 years since prior and no concurrent non-breast malignancy except
nonmelanoma skin cancer or resected stage I ovarian cancer
- No intercurrent illness (e.g., cardiovascular, pulmonary, or central nervous system)
that is either poorly controlled with currently available treatment or that, in the
opinion of the investigator, is deemed unwise to enter the patient on the protocol
- Not pregnant or nursing
- Patients unable to swallow the ABT-888 tablets whole are ineligible; (the tablets
cannot be crushed or broken)
- No active severe infection, including known infection with HIV or hepatitis B or C
virus
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate as measured by RECIST version 1.1
Outcome Time Frame:
Up to 4 years
Safety Issue:
No
Principal Investigator
Jeffrey Weitzel
Investigator Role:
Principal Investigator
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2011-01379
NCT ID:
NCT01149083
Start Date:
June 2010
Completion Date:
Related Keywords:
- brca1 Mutation Carrier
- brca2 Mutation Carrier
- Recurrent Breast Cancer
- Stage IIIB Breast Cancer
- Stage IIIC Breast Cancer
- Stage IV Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| 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 |
