Abstract
Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609).
Keywords:
BRCA1; BRCA2; DNA damage; PARP; PARP inhibitor; PARP trapping; breast cancer; synthetic lethality; veliparib.
Publication types
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Clinical Trial, Phase II
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Randomized Controlled Trial
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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BRCA1 Protein / genetics*
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BRCA2 Protein / genetics*
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Benzimidazoles / administration & dosage
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Benzimidazoles / pharmacokinetics
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics*
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Breast Neoplasms / pathology
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Carboplatin / administration & dosage
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Carboplatin / pharmacokinetics
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Clinical Protocols*
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Dacarbazine / administration & dosage
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Dacarbazine / analogs & derivatives
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Dacarbazine / pharmacokinetics
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Drug Monitoring
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Female
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Humans
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Models, Statistical
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Paclitaxel / administration & dosage
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Paclitaxel / pharmacokinetics
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Research Design
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Sample Size
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Temozolomide
Substances
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BRCA1 Protein
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BRCA2 Protein
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Benzimidazoles
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veliparib
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Dacarbazine
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Carboplatin
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Paclitaxel
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Temozolomide
Associated data
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ClinicalTrials.gov/NCT01506609