Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer
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ClinicalTrials.gov Identifier: NCT01251874 |
Recruitment Status
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Active, not recruiting
First Posted
: December 2, 2010
Last Update Posted
: April 17, 2018
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Tracking Information | ||||
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First Submitted Date ICMJE | December 1, 2010 | |||
First Posted Date ICMJE | December 2, 2010 | |||
Last Update Posted Date | April 17, 2018 | |||
Actual Study Start Date ICMJE | November 16, 2010 | |||
Actual Primary Completion Date | April 12, 2017 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Incidence of adverse events to measure the safety and tolerability of this treatment combination [ Time Frame: Up to 12 weeks post-treatment ] Number and severity of toxicity incidents will be tabulated. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
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Original Primary Outcome Measures ICMJE |
Tolerability as assessed by the number and severity of toxicity incidents evaluated via CTCAE version 4.0 | |||
Change History | Complete list of historical versions of study NCT01251874 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
Clinical response (complete and partial response as well as stable and progressive disease) [ Time Frame: Up to 12 weeks post-treatment ] Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1).
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Original Secondary Outcome Measures ICMJE |
Clinical response (complete and partial response as well as stable and progressive disease) | |||
Current Other Outcome Measures ICMJE |
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Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer | |||
Official Title ICMJE | A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer | |||
Brief Summary | 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 | 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. After completion of study treatment, patients are followed up for 12 weeks. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 1 | |||
Study Design ICMJE | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms | Experimental: 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.
Interventions:
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
44 | |||
Original Estimated Enrollment ICMJE |
42 | |||
Study Completion Date | Not Provided | |||
Actual Primary Completion Date | April 12, 2017 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Senior) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01251874 | |||
Other Study ID Numbers ICMJE | NCI-2011-02552 NCI-2011-02552 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000688990 OSU 10080 8609 ( Other Identifier: Ohio State University Comprehensive Cancer Center ) 8609 ( Other Identifier: CTEP ) P30CA016058 ( U.S. NIH Grant/Contract ) U01CA076576 ( U.S. NIH Grant/Contract ) UM1CA186712 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | National Cancer Institute (NCI) | |||
Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | |||
Verification Date | April 2018 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |