Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
Condition: Platinum Sensitive; BRCA Mutated; Relapsed Ovarian Cancer; Following Complete or Partial Response to Platinum Based Chemotherapy
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hypersensitivity
Intervention: Olaparib 300mg tablets; Placebo to match olaparib 300mg
Intervention description: 300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.; 300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.
Intervention MeSH terms: Olaparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 327.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: BRCA; Ovarian cancer; Chemotherapy; PARP Inhibitor; Platinum sensitive

Summary:

      A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the
      efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer
      (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer)
      or high grade endometrioid cancer with BRCA mutations (documented 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)) who have responded following platinum based
      chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be ≥ 18 years of age.

               -  Female patients with histologically diagnosed relapsed high grade serous ovarian
                  cancer (including primary peritoneal and / or fallopian tube cancer) or high
                  grade endometrioid cancer.

               -  Documented 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).

               -  Patients who have received at least 2 previous lines of platinum containing
                  therapy prior to randomisation

        For the penultimate chemotherapy course prior to enrolment on the study:

        • Patient defined as platinum sensitive after this treatment; defined as disease
        progression greater than 6 months after completion of their last dose of platinum
        chemotherapy

        For the last chemotherapy course immediately prior to randomisation on the study:

          -  Patients must be, in the opinion of the investigator, in response (partial or complete
             radiological response), or may have no evidence of disease (if optimal cytoreductive
             surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125,
             following completion of this chemotherapy course

          -  Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or
             cisplatin) and have received at least 4 cycles of treatment

          -  Patients must be randomized within 8 weeks of their last dose of chemotherapy

          -  Maintenance treatment is allowed at the end of the penultimate platinum regimen,
             including bevacizumab

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

          -  BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g.,
             "Variants of uncertain clinical significance" or "Variant of unknown significance" or
             "Variant, favor polymorphism" or "benign polymorphism" etc.)

          -  Patients who have had drainage of their ascites during the final 2 cycles of their
             last chemotherapy regimen prior to enrolment on the study.