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

This is a phase III, randomized, open label, multicenter, controlled trial of niraparib
versus physician's choice in previously-treated, HER2 negative, germline BRCA
mutation-positive breast cancer patients. Niraparib is an orally active parp inhibitor.
Niraparib (in a 2:1 ratio) will be administered once daily continuously during a 21-day
cycle. Physician's choice will be administered on a 21-day cycle. Health-related quality of
life will be measured. The Safety and tolerability will be assessed by clinical review of
adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory
values.

Inclusion Criteria:

1. Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA
screening criteria will be screened for BRCA mutation.

2. Metastatic or locally advanced disease that is not amenable to resection or radiation
with curative intent.

3. 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 that included a taxane and/or anthracycline, if not contraindicated.

4. 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
(progression during at least one prior hormonal therapy) for which chemotherapy is
indicated.

5. ECOG performance status 0-2

6. Adequate bone marrow, kidney and liver function

Exclusion Criteria:

1. Patients with platinum resistant cancer

2. Symptomatic uncontrolled brain metastases

3. 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

4. Known hypersensitivity to the components of niraparib

5. Invasive cancer other than ovarian cancer within 2 years (except basal or squamous
cell carcinoma of the skin that has been definitely treated)

6. Pregnant or breast feeding patients

7. Immunocompromised patients

8. Known active Hepatitis B or C

9. Prior treatment with a PARP inhibitor

10. Known history of myelodysplastic syndrome (MDS).

11. known and persistent (>4 weeks) >/= grade 3 toxicity or fatigue from prior cancer
treatment.