A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
Condition: Neoplasms, Breast; Carcinoma of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Ovarian Neoplasms
MeSH terms: Carcinoma; Neoplasms; Ovarian Neoplasms; Breast Neoplasms
Intervention: niraparib; Physician's choice
Intervention description: 300 mg (3x100 mg capsules) once daily until progression or unacceptable toxicity develops; Choice of 4 standard of care metastatic breast cancer chemotherapies, until progression or unacceptable toxicity develops
Intervention MeSH terms: Niraparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations.
Masking: None (Open Label)
Enrollment: 216.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; BRCA1 Gene Mutation; BRCA2 Gene Mutation; PARP Inhibitor; BRCA

Summary:

      The purpose of this study is to compare progression-free survival (PFS) in patients with
      advanced/metastatic breast cancer who have a BRCA mutation when treated with niraparib as
      compared to those treated with physician's choice
    

Eligibility criteria:

        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. Histologically or cytologically confirmed HER2-negative 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.

          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; 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.

          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 breast 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.