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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01149083
First received: June 22, 2010
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

This phase II trial is studying giving veliparib together with carboplatin to see how well they work compared to veliparib alone in treating patients with stage III or 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 or by stopping them from dividing. It is not yet known whether veliparib is more effective with or without carboplatin in treating breast cancer.


Condition Intervention Phase
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Drug: veliparib
Drug: carboplatin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate as measured by RECIST version 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 4 years ] [ Designated as safety issue: No ]
    Compared between arms using the log-rank test. Analyzed using Kaplan-Meier plots and multivariate Cox regression.

  • Toxicity graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Assessed and summarized with descriptive statistics.


Estimated Enrollment: 71
Study Start Date: June 2010
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (veliparib)
Patients receive veliparib PO BID on days 1-21.
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (veliparib, carboplatin)
Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in Arm I.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in 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 breast cancer (BRCA)1 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: 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 therapy, patients are followed up every 3-6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  • Measurable disease by Response Evaluation Criteria In Solid Tumors (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 > 4 months
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 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; 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; 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 patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149083

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Siteman Cancer Center at Washington University
Saint Louis, Missouri, United States, 63110
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467-2490
Montefiore Medical Center-Einstein Campus
Bronx, New York, United States, 10461
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
NYU Cancer Institute
New York, New York, United States, 10016
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, Ontario
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Weitzel Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01149083     History of Changes
Other Study ID Numbers: NCI-2011-01379, NCI-2011-01379, CHNMC-PHII-96, CDR0000674384, PHII-96, 8264, N01CM62201, N01CM00032, N01CM00039, N01CM62209, N01CM00038, N01CM00099, N01CM62203, P30CA033572, N01CM00071
Study First Received: June 22, 2010
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014