A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients

Inclusion Criteria

• Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
• Histologically or cytologically confirmed HER2-negative metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
• Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer; patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy.
• Prior therapy should have included a taxane and/or anthracycline (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting. a. Hormone receptor positive patients must also have hormone resistant disease; either relapsed while on adjuvant endocrine treatment, or within one year of completing adjuvant endocrine treatment, or progression on at least one line of endocrine treatment for advanced cancer.
• ECOG performance status 0-2
• Adequate bone marrow, kidney and liver function

Exclusion Criteria

• Patients with platinum resistant cancer
• Symptomatic uncontrolled brain metastases
• Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval; Stage II ovarian cancer must have a 2-year disease-free interval
• Known hypersensitivity to the components of niraparib
• Invasive cancer other than breast cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
• Pregnant or breast feeding patients
• Immunocompromised patients
• Known active Hepatitis B or C
• Prior treatment with a PARP inhibitor
• Known history of myelodysplastic syndrome (MDS).
• known and persistent (>4 weeks) >/= grade 3 toxicity or fatigue from prior cancer treatment.