Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Olaparib; Placebo
Intervention description: Patients will be administred olaparib orally twice daily (b.i.d.) 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.; Patients will be administred matching placebo. Two (2) 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.
Intervention MeSH terms: Olaparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1836.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Breast Cancer; Adjuvant; Olaparib; BRCA 1/2; HER2

Summary:

      Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative
      primary breast cancer who have completed definitive local treatment and neoadjuvant or
      adjuvant chemotherapy
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
             that is one of the following phenotypes:

               1. Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative
                  (not eligible for anti-HER2 therapy)

               2. ER and/or PgR positive, HER2 negative

          -  Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or
             suspected deleterious (known or predicted to be detrimental/lead to loss of function).

          -  Completed adequate breast and axilla surgery.

          -  Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing
             anthracyclines, taxanes or the combination of both. Prior platinum as potentially
             curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant
             treatment for breast cancer is allowed.

          -  ECOG 0-1.

        Exclusion criteria:

          -  Any previous treatment with a PARP inhibitor, including olaparib and/or known
             hypersensitivity to any of the excipients of study treatment.

          -  Patients with second primary malignancy. EXCEPTIONS are:

               1. adequately treated non-melanoma skin cancer, curatively treated in situ cancer of
                  the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1
                  endometrial carcinoma

               2. other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5
                  years prior to randomisation and treated with no evidence of disease recurrence
                  and for whom no more than one line of chemotherapy was applied.

          -  Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.,
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
             period prior to starting study treatment is 2 weeks. Concomitant use of known strong
             (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine,
             carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g.,
             bosentan, efavirenz, modafinil). The required washout period prior to starting study
             treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.

          -  Evidence of metastatic breast cancer