Multi-maintenance Olaparib After Disease Recurrence in Participants With Platinum Sensitive BRCAm High Grade Serous Ovarian Cancer

Inclusion Criteria:

1. Progressive, measureable high grade serous or endometrioid ovarian cancer, fallopian tube or primary peritoneal cancer

   * Participants who have not been treated with PARP inhibitor previously will be treated with two maintenance courses of olaparib.
   * Participants, who have received one course of maintenance olaparib before entry to the trial, will only receive one further course of treatment.
2. Aged 18 or over
3. Measureable disease by RECIST 1.1
4. ECOG performance status 0-2 and life expectancy of over 12 weeks
5. Adequate haematological function: Hb ≥ 10.0 g/l, Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l; coagulation: INR \<1.4 (unless therapeutically anti-coagulated) and/or APPT ratio \<1.4
6. Adequate liver function: bilirubin ≤1.5 x ULN, Transaminases (ALT and AST) ≤2.5x ULN unless liver metastases are present in which case they must be ≤ 5x ULN
7. Adequate renal function defined as GFR ≥ 51ml/min
8. Written, informed consent that includes genetic research on tissue derived from biopsies.
9. Pathogenic germline BRCA-1 or -2 gene mutation
10. Ability to swallow oral medication (tablets).

Exclusion Criteria:

1. Concurrent medical illness that would impact on compliance with the protocol including MDS/ AML
2. Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required.
3. Known positivity for Hep B, Hep C or HIV.
4. Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
5. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
6. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
7. Another cancer, which has been active within the previous 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and no evidence of recurrence of other malignancy.
8. Female participants who are able to become pregnant (or are already pregnant or lactating) unless the following apply: Those who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for one month afterwards are considered eligible. Alternatively if the participant can abstain from sexual intercourse for the same interval, then they are eligible to participate.
9. Participants who are planning to receive maintenance bevacizumab.
10. Participants will be excluded if the side effects of previous treatments have not resolved to grade I or less, with the exception of alopecia or grade 2 neurotoxicity that is considered related to cytotoxic chemotherapy.
11. Radiotherapy, surgery or tumour embolization within 28 days before the cycle 1 day 1 of the platinum-containing chemotherapy.
12. Additional concurrent anti-cancer therapy.
13. Causes of malabsorption e.g. uncontrolled diarrhoea or poorly controlled stoma is not permitted.
14. Participants who have contra-indications to VEGF inhibitors will not be eligible to receive cediranib (second treatment). These contra-indications include concurrent or past history of malignant fistula, uncontrolled hypertension, recent arterial thrombosis (cerebrovascular accident or myocardial infarction) within the past 6 months, participants who are at risk of bowel perforation, proteinuria greater than 2g/24 hours or a past history of VEGF inhibitor-associated reversible posterior leukoencephalopathy.
15. Any participant that is participating in another interventional clinical trial within 30 days or 5-lives prior to signing of consent. Participation in an observational trial would be acceptable.