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

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ClinicalTrials.gov Identifier: NCT01149083
Recruitment Status : Active, not recruiting
First Posted : June 23, 2010
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies how well veliparib with or without carboplatin works in treating patients with 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, 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.

Condition or disease Intervention/treatment Phase
Locally Advanced Breast Carcinoma Metastatic Breast Carcinoma Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7 Unresectable Breast Carcinoma Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Veliparib Phase 2

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 s a dose-escalation study of veliparib. 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 treatment, patients are followed up every 3-6 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 71 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : June 30, 2010
Estimated Primary Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: Arm I (veliparib)
Patients receive veliparib PO BID on days 1-21.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888

Experimental: Arm II (veliparib, carboplatin)
Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in Arm I.
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

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888




Primary Outcome Measures :
  1. Response rate [ Time Frame: Up to 4 years ]
    Measured by Response Evaluation Criteria in Solid Tumors version 1.1.


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 4 years ]
    Compared between arms using the log-rank test. Analyzed using Kaplan-Meier plots and multivariate Cox regression.

  2. Toxicity [ Time Frame: Up to 4 years ]
    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and 5.0. Assessed and summarized with descriptive statistics.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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). 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01149083


Locations
Show Show 23 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Joanne Mortimer City of Hope Comprehensive Cancer Center
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01149083    
Other Study ID Numbers: NCI-2011-01379
NCI-2011-01379 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHII-96
CHNMC-PHII-96
CDR0000674384
8264 ( Other Identifier: City of Hope Comprehensive Cancer Center )
8264 ( Other Identifier: CTEP )
N01CM00032 ( U.S. NIH Grant/Contract )
N01CM00038 ( U.S. NIH Grant/Contract )
N01CM00039 ( U.S. NIH Grant/Contract )
N01CM00071 ( U.S. NIH Grant/Contract )
N01CM00099 ( U.S. NIH Grant/Contract )
N01CM62201 ( U.S. NIH Grant/Contract )
N01CM62202 ( U.S. NIH Grant/Contract )
N01CM62203 ( U.S. NIH Grant/Contract )
N01CM62209 ( U.S. NIH Grant/Contract )
P30CA033572 ( U.S. NIH Grant/Contract )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: June 23, 2010    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: February 2021
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carboplatin
Veliparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action