Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.
Condition: Newly Diagnosed; Advanced Ovarian Cancer; FIGO Stage III-IV; BRCA Mutation; Complete Response; Partial Response; First Line Platinum Chemotherapy
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Olaparib 300mg tablets
Intervention description: Olaparib/placebo tablets p.o 300mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. 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: 450.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: BRCA; Ovarian Cancer; Chemotherapy; PARP inhibitor; First Line; FIGO Stage III; FIGO Stage IV

Summary:

      Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line
      Platinum Based Chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patients with newly diagnosed, histologically confirmed, high risk advanced
             (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid
             ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have
             completed first line platinum based chemotherapy (intravenous or intraperitoneal).

          -  Stage III patients must have had one attempt at optimal debulking surgery (upfront or
             interval debulking). Stage IV patients must have had either a biopsy and/or upfront or
             interval debulking surgery.

          -  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 completed first line platinum (e.g. carboplatin or cisplatin),
             containing therapy (intravenous or intraperitoneal) prior to randomisation:

          -  Patients must have, in the opinion of the investigator, clinical complete response or
             partial response and have no clinical evidence of disease progression on the post
             treatment scan or rising CA-125 level, following completion of this chemotherapy
             course. Patients with stable disease on the post-treatment scan at completion of first
             line platinum-containing therapy are not eligible for the study.

          -  Patients must be randomized within 8 weeks of their last dose of chemotherapy

        Exclusion Criteria:

          -  BRCA1 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 with early stage disease (FIGO Stage I, IIA, IIB or IIC)

          -  Stable disease or progressive disease on the post-treatment scan or clinical evidence
             of progression at the end of the patient's first line chemotherapy treatment.

          -  Patients where more than one debulking surgery has been performed before randomisation
             to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable
             and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and
             interval debulking surgery are eligible).

          -  Patients who have previously been diagnosed and treated for earlier stage ovarian,
             fallopian tube or primary peritoneal cancer.

          -  Patients who have previously received chemotherapy for any abdominal or pelvic tumour,
             including treatment for prior diagnosis at an earlier stage for their ovarian,
             fallopian tube or primary peritoneal cancer. (Patients who have received prior
             adjuvant chemotherapy for localised breast cancer may be eligible, provided that it
             was completed more than three years prior to registration, and that the patient
             remains free of recurrent or metastatic disease).

          -  Patients with synchronous primary endometrial cancer unless both of the following
             criteria are met: 1) stage <2 2) less than 60 years old at the time of diagnosis of
             endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid
             adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with
             Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell
             adenocarcinoma or carcinosarcoma of the endometrium are not eligible.