Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
Condition: Breast Cancer Metastatic; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation
MeSH terms: Breast Neoplasms
Intervention: Olaparib; Physician's choice chemotherapy
Intervention description: Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.; Investigators will declare one of the following regimens:
Capecitabine 2500 mg/m2 po daily (divided in 2 doses) x 14 days, repeat every 21 days
Vinorelbine 30 mg/m2 IV Day 1 and Day 8, repeat every 21 days
Eribulin 1.4 mg/m2 IV Day 1 and Day 8, repeat every 21 days
Intervention MeSH terms: Olaparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Breast Cancer; Metastatic; Olaparib; BRCA; PARP inhibitor; HER2; chemotherapy

Summary:

      This open label, randomised, controlled, multi-centre phase III study will assess the
      efficacy and safety of single agent olaparib vs standard of care based on physician's choice
      of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2
      mutations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected
             deleterious.

          -  Histologically or cytologically confirmed breast cancer with evidence of metastatic
             disease.

          -  Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic
             setting.

          -  Prior platinum allowed as long as no breast cancer progression occurred on treatment
             or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study
             entry elapsed.

          -  ER/PR breast cancer positive patients must have received and progressed on at least
             one endocrine therapy (adjuvant or metastatic), or have disease that the treating
             physician believes to be inappropriate for endocrine therapy.

          -  ECOG performance status 0-1.

          -  Adequate bone marrow, kidney and liver function.

        Exclusion Criteria:

          -  Prior treatment with PARP inhibitor.

          -  Patients with HER2 positive disease.

          -  More than 2 prior lines of chemotherapy for metastatic breast cancer.

          -  Untreated and/or uncontrolled brain metastases.

          -  Prior malignancy unless curatively treated and disease-free for > 5 years prior to
             study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the
             cervix, DCIS or stage I grade 1 endometrial cancer allowed.

          -  Known HIV (Human Immunodeficiency Virus) infection.

          -  Pregnant or breast-feeding women.