Breast Cancer Clinical Trial
Veliparib With or Without Carboplatin in Treating Patients With Stage IV Breast Cancer
Summary
This phase II trial studies how well veliparib with or without carboplatin works in treating patients with stage IV breast cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether veliparib is more effective with or without carboplatin in treating breast cancer.
Full Description
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of single agent veliparib (ABT-888) (NSC 737664) in breast cancer (BRCA) carriers with metastatic breast cancer based on response rate (Response Evaluation Criteria In Solid Tumors [RECIST] criteria).
SECONDARY OBJECTIVES:
I. To conduct subset analysis on BRCA1 versus (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: This s a dose-escalation study of veliparib. 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 treatment, patients are followed up every 3-6 months.
Eligibility Criteria
Inclusion Criteria:
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). It is expected that BRCA testing will be covered as medically necessary care by the patient's insurance carrier
Measurable disease by 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 greater than four months
Absolute neutrophil count (ANC) >= 1,500/mcL
Platelets >= 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; (The effects of ABT-888 [NSC 737664] on the developing human fetus are unknown; for this reason and because PARP Inhibitor agents are known to be teratogenic, 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
Exclusion Criteria:
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 because ABT-888 (NSC 737664) has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ABT-888 (NSC 737664), 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-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ABT-888 (NSC 737664); in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
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There are 20 Locations for this study
Duarte California, 91010, United States
Los Angeles California, 90033, United States
Sacramento California, 95817, United States
Aurora Colorado, 80045, United States
Jacksonville Florida, 32224, United States
Chicago Illinois, 60637, United States
Baltimore Maryland, 21287, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Boston Massachusetts, 02215, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
Saint Louis Missouri, 63110, United States
Bronx New York, 10461, United States
Bronx New York, 10467, United States
New York New York, 10016, United States
New York New York, 10065, United States
New York New York, 10065, United States
Hershey Pennsylvania, 17033, United States
Pittsburgh Pennsylvania, 15213, United States
Pittsburgh Pennsylvania, 15232, United States
Houston Texas, 77030, United States
Toronto Ontario, M5G 2, Canada
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