Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer
A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer
7 other identifiers
interventional
44
1 country
3
Brief Summary
This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin and to see how well they work in treating patients with human epidermal growth factor 2 (HER2)-negative breast cancer that has spread to other parts of the body. Carboplatin kills cancer cells by damaging the deoxyribonucleic acid (DNA) that lets the cancer cell survive and reproduce. The body has proteins that try to repair the damaged DNA. Veliparib may prevent these proteins from repairing the DNA so that carboplatin may be able to kill more tumor cells. Giving veliparib with carboplatin may kill more tumor cells than carboplatin alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2010
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 22, 2010
CompletedFirst Submitted
Initial submission to the registry
December 1, 2010
CompletedFirst Posted
Study publicly available on registry
December 2, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
November 19, 2026
ExpectedNovember 21, 2025
November 1, 2025
13.9 years
December 1, 2010
November 20, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events to measure the safety and tolerability of this treatment combination
Number and severity of toxicity incidents will be tabulated. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
Up to 12 weeks post-treatment
Secondary Outcomes (1)
Clinical response (complete and partial response as well as stable and progressive disease)
Up to 12 weeks post-treatment
Other Outcomes (3)
PARP-1 activity
Up to 5 years
Thymidine kinase uptake on 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) scans
Up to 18 weeks (after course 3)
Circulating tumor cell markers
Up to 5 years
Study Arms (1)
Treatment (veliparib, F 18 fluorothymidine, carboplatin)
EXPERIMENTALPatients receive carboplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.
Interventions
Undergo collection of blood sample
Given IV
Undergo PET/CT
Given FLT
Undergo PET/CT
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically proven metastatic or locally advanced inoperable breast cancer that fulfills one of the following two criteria:
- Triple-negative breast cancer
- ER and/or PR positive, HER2 negative if their tumors have been shown to be deficient for the FA pathway, based on FA triple stain immunofluorescence (FATSI) screening
- HER negative with a known germline BRCA1/2 mutation
- Patients with ER- and/or PR-positive breast cancer will be consented to have their existing, or to be obtained, paraffin-embedded tumor tissue screened for FA deficiency
- No more than 3 prior chemotherapy regimens for metastatic disease will be allowed; any number of prior hormone therapies will be allowed; however, at least 4 weeks should have elapsed since prior chemotherapy (6 weeks for mitomycin C and nitrosoureas and 2 weeks for hormone therapy) or radiation therapy (2 weeks for limited field palliative radiation to the bone)
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Patients with treated brain metastases and life expectancy of greater than 3 months
- Patients with known Gilbert syndrome with abnormal unconjugated bilirubin will be eligible
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic acid transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X 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
- No prior therapy with veliparib for metastatic disease will be allowed
- +3 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- Known human immunodeficiency virus (HIV)-infected patients on protease inhibitors are ineligible; HIV-infected patients with adequate cluster of differentiation (CD)4 counts (\> 500) and not on protease inhibitors are eligible
- Patients with active seizure or a history of seizures are not eligible
- Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases must be stable after therapy for \> 3 months and off steroid treatment prior to study enrollment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kai C Johnson
Ohio State University Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 1, 2010
First Posted
December 2, 2010
Study Start
November 22, 2010
Primary Completion
September 30, 2024
Study Completion (Estimated)
November 19, 2026
Last Updated
November 21, 2025
Record last verified: 2025-11