OPINION - A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed non-Germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy

For inclusion in the study patients should fulfill all of the following criteria:
1. Provision of informed consent prior to any study specific procedures
2. Patients must be *18 years of age
3. Female patients with histologically diagnosed relapsed HGSOC (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid ovarian cancer
4. Documented gBRCA1/2 mutation status
Evidence that the patients do not have a gBRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). gBRCA1 and/or gBRCA2 variants that are classified as *Variants of uncertain clinical significance* or *Variant of unknown significance (VUS)* are eligible, as well as *Variant, favor polymorphism* or *benign polymorphism*. ;Evidence of the absence of a somatic BRCA mutation is not required. Patients with a tumour BRCA test result only must undergo a gBRCA test to determine whether the BRCA aberration is germline or somatic in origin. If this analysis identifies the aberration as germline the patient is not eligible ;5. Patients must have completed at least 2 previous courses of platinum containing therapy:
(a) For the penultimate chemotherapy course prior to enrolment on the study:;* Treatment must have contained a platinum agent (e.g. carboplatin, cisplatin or oxaliplatin per standard clinical practice; there are no other specific requirements);* Patient was platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy;* Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab;(b) 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), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, as defined below, following completion of this chemotherapy course;* Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin, cisplatin or oxaliplatin) and have received at least 4 cycles of treatment;* Patients must not have received bevacizumab during this course of treatment;* Patients must not have received any investigational agent during this course of treatment;* Patients must initiate treatment within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion);6. Pre-treatment CA-125 measurements must meet criterion specified below:;* If the first value is within upper limit of normal (ULN) the patient is eligible to be enrolled and a second sample is not required;* If the first value is greater than ULN a second assessment must be performed at least 7 days after the 1st. If the second assessment is * 15% more than the first, the patient is not eligible;7. Patients must have normal organ and bone marrow function measured within 28 days of starting study treatment, as defined below. In the event of minor deviations from these values which would lead to screen failure, repeat testing within the 28-day screening period (limited to the tests listed below) is allowed before the patient is declared a screen failure.
* Haemoglobin *10.0 g/dL with no blood transfusion in the past 28 days
* Absolute neutrophil count (ANC) *1.5 X 109/L
* Platelet count *100 X 109/L
* Total bilirubin (TBL) *1.5 X 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 *5 X ULN
* Patients must have creatinine clearance, estimated (below), or based on a 24 hour urine test, using the Cockcroft-Gault equation of *51 mL/min:
Estimated creatinine clearance (females) <= (140-age [years]) x weight (kg) x 0.85
serum creatinine (mg/dL) x 72

8. ECOG performance status 0-1
9. Patients must have a life expectancy *16 weeks
10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
Postmenopausal is defined as any of the following:
* Amenorrhoeic 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 >1 year interval since last menses
* Surgical sterilisation (bilateral oophorectomy or hysterectomy).
11. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
12. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment
OR
No evidence of disease following a complete response to chemotherapy (with or without cytoreductive surgery)
13. An appropriately prepared tumour sample from the cancer, of sufficient quantity and quality (as specified in the Central Laboratory Services Manual) must be available for future central testing of tumour genetic status. If a recent biopsied sample is provided, the biopsied tumour should not be assessed as target lesions as part of the RECIST assessments if there are other lesions available, and the biopsy should be taken after the baseline scan has been performed. Archival tissue samples may be from the primary tumour or metastatic tumour deposits. Archival bone metastases are not acceptable. Provision of blocks is usually preferred. Any exceptions to these conditions should be discussed with the Sponsor before enrollment of the patient.

Patients should not enter the study if any of the following exclusion criteria are fulfilled.
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site*
2. Previous enrolment in the present study*
3. Participation in another clinical study with an investigational product (IP) during the most recent chemotherapy course*
4. Patients receiving any systemic hormonal therapy, chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to start of study treatment
5. Any previous treatment with PARP inhibitor, including olaparib*
6. Patients with a germline BRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function).
7. Other malignancy unless curatively treated with no evidence of disease for > 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma
8. 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 olaparib is 2 weeks*.
9. Concomitant use of known strong (e.g., phenobarbital, 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 olaparib is 5 weeks for phenobarbital and 3 weeks for other agents*
10. Persistent toxicities (* Grade 2 Common Terminology Criteria for Adverse Event (CTCAE) adverse event) caused by previous cancer therapy, excluding alopecia
11. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML*
12. 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*
13. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
14. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication*
16. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding women*
17. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C*
18. Patients with a known hypersensitivity to olaparib or any of the excipients of the product*
19. Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids*
20. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)*
21. Patients having gBRCA testing should not have had whole blood transfusions in the last 30 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)
22. Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely or unable to comply with study procedures, restrictions and requirements.