To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer
Condition: BRCA or HRR+ Mutated Ovarian Cancer Patients
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Olaparib
Intervention description: Olaparib Capsule - 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage.
Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily.
Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water.
Intervention MeSH terms: Olaparib
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 181.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      This is a prospective, open-label, single arm, multi-center study to assess the real world
      clinical effectiveness and safety of olaparib maintenance monotherapy as the capsule
      formulation (in line with the EU approved prescribing information) and will be conducted in
      platinum-sensitive relapsed high grade epithelial ovarian cancer patients (including patients
      with primary peritoneal and / or fallopian tube cancer) who carry germline or somatic 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]).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of informed consent prior to any study specific procedures

          2. Age 18 years or over

          3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to
             be deleterious or suspected deleterious (known or predicted to be detrimental/lead to
             loss of function) [Genetic counselling for patients with germline BRCA mutations
             should be performed according to local regulations] Or Tumour BRCAwt status and
             documented qualifying mutation in any of 13 genes involved in the HRR pathway,
             excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1,CDK12, CHEK1, CHEK2, FANCL, PALB2,
             PPP2R2A, RAD51B, RAD51C, RAD51D,and RAD54L), identified by the Lynparza HRR Assay in
             archival tumour tissue (i.e.,BRCA-independent HRRm)

          4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers
             (including primary peritoneal and/or fallopian tube cancer):

             - Platinum sensitive disease is defined as disease progression ≥6 months after
             completion of their last dose of platinum based chemotherapy

          5. Patients should have received at least 2 previous lines of platinum containing therapy
             prior to enrolment:

             - For the last chemotherapy course immediately prior to enrolment on the study,
             patients must be, in the opinion of the investigator, in response (partial or complete
             radiological response) and no evidence of a rising CA-125, following completion of
             this chemotherapy course.

          6. Patients must have normal organ and bone marrow function measured within 28 days of
             enrolment, as defined below:

               -  Haemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               -  Platelet count ≥ 100 x 109/L

          7. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), Aspartate
             aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase [SGOT]) / Alanine
             aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase [SGPT]) ≤ 2.5 x
             institutional ULN unless liver metastases are present in which case they must be ≤ 5x
             ULN

          8. Creatinine clearance > 50 ml/min (calculated)

          9. Patients must be postmenopausal or have evidence of non-childbearing status for women
             of childbearing potential.

        Postmenopausal is defined as any of the following:

          -  Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments

          -  For women under 50 years old, luteinizing hormone (LH) and follicle stimulating
             hormone (FSH) levels in the post-menopausal range

          -  Radiation-induced oophorectomy, with interval of 1 year or more since last menses

          -  Chemotherapy-induced menopause, with interval of 1 year or more since last menses

          -  Surgical sterilisation (bilateral oophorectomy or hysterectomy).

        Exclusion Criteria:

          1. Patients previously diagnosed with gBRCAm disease

          2. Participation in another clinical study with an investigational product during the
             most recent chemotherapy course

          3. Patients with a known hypersensitivity to olaparib or any of the excipients of the
             product

          4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
             reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery
             within 3 weeks of starting study treatment and patients must have recovered from any
             effects of any major surgery

          5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2
             caused by previous cancer therapy, excluding alopecia

          6. Patients with myelodysplastic syndrome/acute myeloid leukaemia

          7. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring
             treatment or active Hepatitis B or C

          8. Patients with symptomatic uncontrolled brain metastases. The patient can receive a
             stable dose of corticosteroids before and during the study as long as these were
             started at least 4 weeks prior to treatment. Patients with spinal cord compression
             unless considered to have received definitive treatment for this and evidence of
             clinically stable disease (SD) for 28 days

          9. Patients considered to be at a high medical risk due to a serious, uncontrolled
             medical disorder, systemic disease or active, uncontrolled infection

         10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.