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
Rochester, Minn., Jacksonville, Fla.
Trial status: Open for Enrollment
Why is this study being done?
I. To evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in BRCA carriers with metastatic breast cancer based on response rate (Response Evaluation Criteria In Solid Tumors [RECIST] criteria).
I. To conduct subset analysis on breast cancer (BRCA)1 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 poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibition by ABT-888 and biomarkers of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cell (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: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-21.
ARM II: Patients receive carboplatin intravenously (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.
After completion of study therapy, patients are followed up every 3-6 months.
Who is eligible to participate?
- Patients must be female, and must have histologically confirmed breast cancer that is metastatic or locally advanced, unresectable and for which standard curative measures do not exist or are no longer effective
- Patient must have a known deleterious BRCA mutation confirmed by report from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (generally Myriad Genetics Laboratory)
- Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; (evaluable disease is allowed only for the Safety Lead-In phase)
- Prior chemotherapy regimens for metastatic disease are completed, at least 3 weeks prior to starting therapy; prior radiation and hormonal treatment must be completed at least 1 week prior to starting therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy > 4 months
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelet count >= 100,000/mcL
- Total bilirubin =< 1.5 times institutional upper limit of normal
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 times institutional upper limit of normal unless there is evidence of liver metastasis, in which case the AST (SGOT)/ALT (SGPT) must be =< 5 times institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- If a woman is of child-bearing potential, a negative serum or urine pregnancy test is required; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; participants should agree to use contraception for at least 3 months after the completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Prior therapy with platinum agents (adjuvant therapy with platinum agents is allowed, if completed >= 12 months prior to relapse), or PARP inhibitors (prior iniparib, since it is no longer considered a PARP inhibitor, is allowed)
- Patients may not be receiving any other investigational agents
- Patients with known central nervous system (CNS) metastases requiring anticonvulsive medications, or steroids or with active symptomatology; patients on anticonvulsant medications prescribed for reasons other than CNS metastases, not on steroids and without active symptomatology are eligible; patients must be off anti-seizure medications and steroids for 3 months or more before enrollment
- 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
- History of allergic reactions attributed to compounds of similar chemical or biological composition to ABT-888 (NSC 737664) or PARP Inhibitors
- Patients with contraindications to platinum agents are excluded
- Prior or current non-breast malignancy within 5 years except non-melanoma skin cancer or resected stage I ovarian cancer
- Patients with any non-malignant intercurrent illness (e.g., cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol
- Pregnant women are excluded from this study; breastfeeding should be discontinued
- Patients unable to swallow the ABT-888 tablets whole are ineligible; (the tablets cannot be crushed or broken)
- Patients with an active severe infection; known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus; HIV patients on combination antiretroviral therapy are ineligible