Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer

NCT ID: NCT01251874

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-22

Study Completion Date

2026-11-19

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose of veliparib along with carboplatin on a 14-day and 21-day schedule in patients with Her2 negative metastatic breast cancer that are estrogen receptor (ER)/progesterone receptor(PR) negative or ER and/or PR positive with defects in Fanconi Anemia (FA) pathway repair genes.

II. To determine the safety and tolerability of combining veliparib on a 14-day and 21-day schedule with carboplatin in this patient population.

III. To determine the preliminary efficacy of this combination in this patient population.

SECONDARY OBJECTIVES:

I. To determine the pharmacodynamic endpoints of poly(ADP-ribose) polymerase (PARP) inhibition in the tumor by using, A) 3'-\[F-18\]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) of the target lesions, B) circulating tumor cells to detect the induction of the histone variant gamma H2AX, and C) peripheral blood mononuclear cells to assess poly ADP-Ribose (PAR) levels.

II. To determine biomarkers in the primary tumor that may predict antitumor responses to PARP inhibition such as breast cancer 1/2, early onset (BRCA)1/2 protein, Fanconi anemia, complementation group D2 (FANCD2) nuclear foci formation and expression of micro-ribonucleic acid (RNA) 155 (miR 155).

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive carboplatin intravenously (IV) over 1 hour on day 1 and veliparib orally (PO) twice daily (BID) on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients also undergo collection of blood sample, positron emission tomography (PET)/computed tomography (CT) throughout the study.

After completion of study treatment, patients are followed up for 12 weeks.

Conditions

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Recurrent Breast Carcinoma Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7 Triple-Negative Breast Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (veliparib, F 18 fluorothymidine, carboplatin)

Patients 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood sample

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Fluorothymidine F-18

Intervention Type OTHER

Given FLT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Veliparib

Intervention Type DRUG

Given PO

Interventions

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Biospecimen Collection

Undergo collection of blood sample

Intervention Type PROCEDURE

Carboplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Fluorothymidine F-18

Given FLT

Intervention Type OTHER

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Veliparib

Given PO

Intervention Type DRUG

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography 18F-FLT 3'-Deoxy-3'-(18F) Fluorothymidine 3'-deoxy-3'-[18F]fluorothymidine ALOVUDINE F-18 Fluorothymidine F 18 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT ABT 888 ABT-888 ABT888 PARP-1 inhibitor ABT-888

Eligibility Criteria

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Inclusion Criteria

* 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
* 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; 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
* Patients must be able to swallow pills

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kai C Johnson

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

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Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-02552

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000688990

Identifier Type: -

Identifier Source: secondary_id

OSU 10080

Identifier Type: -

Identifier Source: secondary_id

8609

Identifier Type: OTHER

Identifier Source: secondary_id

8609

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186712

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02552

Identifier Type: -

Identifier Source: org_study_id

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