Veliparib With or Without Carboplatin in Treating Patients With Stage III or IV Breast Cancer

NCT ID: NCT01149083

Last Updated: 2025-08-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2024-09-30

Brief Summary

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This phase II trial studies how well veliparib with or without carboplatin works in treating patients with stage III or 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.

Detailed Description

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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 is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 phases.

SAFETY LEAD-IN PHASE: Patients receive veliparib orally (PO) twice daily (BID) on days 1-21 of each cycle and carboplatin intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and may optionally undergo biopsies throughout the study. Patients undergo blood sample collection during screening and on study.

PHASE II: Patients receive veliparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients are taken off treatment for 1 week and may then continue to recieve veliparib along with carboplatin IV over 30 minutes on day 1 of each cycle. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and may optionally undergo biopsies throughout the study. Patients undergo blood sample collection during screening and on study.

\* As of the November 9, 2023 amendment, the pharmaceutical collaborator has discontinued the ABT-888 development program with the National Cancer Institute Cancer Therapy Evaluation Program (CTEP). Clinical supply will no longer be available after December 31, 2024. Patients will discontinue treatment by December 31, 2024, or earlier.

After completion of study treatment, patients are followed up every 6 months.

Conditions

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Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 Locally Advanced Breast Carcinoma Metastatic Breast Carcinoma Unresectable Breast Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase II (veliparib, carboplatin)

Patients receive veliparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients are taken off treatment for 1 week and may then continue to recieve veliparib along with carboplatin IV over 30 minutes on day 1 of each cycle. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and may optionally undergo biopsies throughout the study. Patients undergo blood sample collection during screening and on study.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Veliparib

Intervention Type DRUG

Given PO

Safety Lead-In Phase (veliparib, carboplatin)

Patients receive veliparib PO BID twice daily on days 1-21 of each cycle and carboplatin IV over 30 minutes on day 1 of each cycle. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and may optionally undergo biopsies throughout the study. Patients undergo blood sample collection during screening and on study.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Veliparib

Intervention Type DRUG

Given PO

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Carboplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Veliparib

Given PO

Intervention Type DRUG

Other Intervention Names

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BIOPSY_TYPE Bx 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 tomography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI ABT 888 ABT-888 ABT888 PARP-1 inhibitor ABT-888

Eligibility Criteria

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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
* Patients 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
* Female, age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ABT-888 in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy of 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

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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Joanne Mortimer

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center at Washington University

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

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

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

UPMC-Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Egger SJ, Chan MMK, Luo Q, Wilcken N. Platinum-containing regimens for triple-negative metastatic breast cancer. Cochrane Database Syst Rev. 2020 Oct 21;10(10):CD013750. doi: 10.1002/14651858.CD013750.

Reference Type DERIVED
PMID: 33084020 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2011-01379

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHII-96

Identifier Type: -

Identifier Source: secondary_id

CHNMC-PHII-96

Identifier Type: -

Identifier Source: secondary_id

CDR0000674384

Identifier Type: -

Identifier Source: secondary_id

8264

Identifier Type: OTHER

Identifier Source: secondary_id

8264

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00038

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00039

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00099

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62202

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62203

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62209

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01379

Identifier Type: -

Identifier Source: org_study_id

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