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

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

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.

Study Overview

• Status: Completed
• Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Unresectable Breast Carcinoma; Metastatic Breast Carcinoma; Locally Advanced Breast Carcinoma
• Intervention / Treatment: Drug: Carboplatin; Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Biopsy; Drug: Veliparib

Detailed 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 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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Washington University
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; JM8; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Veliparib; Given PO; Other Names: ABT-888; PARP-1 inhibitor ABT-888; ABT 888; ABT888
Experimental: 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.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; JM8; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Veliparib; Given PO; Other Names: ABT-888; PARP-1 inhibitor ABT-888; ABT 888; ABT888

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival will be summarized as time from first protocol treatment until progression or death from any cause, using the product-limit Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From start of treatment to time of progression or death from any cause, whichever occurs first, assessed up to at least 1 year
Number of Subject With Overall Response	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm; Partial Response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Overall Response (OR) = CR + PR	Up to 8 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival will be summarized as time from first protocol treatment until death from any cause, using the product-limit Kaplan-Meier estimator.	From start of treatment to time of death from any cause, assessed up to at least 3 years
Maximum Tolerated Dose (MTD)	The maximum tolerated dose of veliparib in combination with AUC 5 of Carboplatin is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.	21 days from start of treatment, up to 2 years
Number of Participants With at Least One Dose Limiting Toxicity (DLT) - Phase I	Dose-limiting toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Pre-specified DLT criteria included the following adverse events (AE), judged to be at least possibly related to study therapy: any grade III non-hematological toxicity not reversible to grade II or less within 96 hours, or any grade IV toxicity (excluding alopecia or controllable nausea and vomiting). Additionally, patients unable to take 80% of the planned ABT-888 due to toxicity/tolerability will be considered to have had a DLT.	During the first cycle of treatment, up to 21 days

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joanne Mortimer, City of Hope Comprehensive Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2010
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimated): June 23, 2010

Study Record Updates

• Last Update Posted (Actual): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Carcinoma; Breast Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carboplatin; Veliparib
• Other Study ID Numbers: NCI-2011-01379 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); P30CA033572 (U.S. NIH Grant/Contract); N01CM62202 (U.S. NIH Grant/Contract); N01CM62203 (U.S. NIH Grant/Contract); U10CA180821 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); N01CM00039 (U.S. NIH Grant/Contract); N01CM00071 (U.S. NIH Grant/Contract); N01CM00099 (U.S. NIH Grant/Contract); N01CM00038 (U.S. NIH Grant/Contract); N01CM00032 (U.S. NIH Grant/Contract); PHII-96; CHNMC-PHII-96; CDR0000674384; 8264 (Other Identifier: CTEP)