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Inclusion Criteria: Prior to paclitaxel and cediranib

1. Histologically confirmed, progressive, platinum-resistant or refractory, high-grade ovarian, fallopian tube or primary peritoneal cancer for which weekly paclitaxel would be a potential treatment option
2. Aged 16 years or over
3. At risk of bowel obstruction: features compatible with this include increasing abdominal pain and swelling, borborygmi, change in bowel habit, extensive serosal disease or dilated or tethered bowel on radiological investigation. One or more of these should be present in eligible patients. Previous bowel obstruction is permitted providing patients can take oral medication and there is no concern about absorption of oral medication. Recto sigmoid involvement is permitted
4. Adequate haematological function: Hb ≥ 100 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
5. Adequate renal function defined as GFR ≥50ml/min and Creatinine clearance ≥50 mL/min using modified Wright or Cockcroft-Gault formula
6. Adequate liver function: bilirubin ≤ 1.5 x ULN, transaminases ≤ 3 x ULN
7. Any number of previous anti-cancer treatments permitted including weekly paclitaxel in the first-line setting
8. Controlled hypertension permitted. Patients must have a blood pressure (BP) of ≤ Systolic BP (SBP):150/ Diastolic BP (DBP) 90 mmHg, with or without anti-hypertensive medication. BP measurements must be taken in the clinic setting by a medical professional within 2 weeks prior to starting study. A maximum of 3 anti-hypertensive medications are permitted and it is strongly recommended that patients who are on 3 anti-hypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on study
9. ECOG performance status 0-2 and life expectancy of over 12 weeks.
10. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
11. Measurable disease by RECIST v1.1
12. Previous bevacizumab is permitted but patients cannot have been treated with VEGF RTKi previously
13. Written informed consent
14. Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib.

Inclusion Criteria: Prior to switching to olaparib and cediranib

1. Radiological evidence of PD that is measurable per RECIST v1.1
2. Meet inclusion criteria listed previously as points: 4-6, 8-10, 14
3. No contra-indications to receive cediranib or olaparib.

Exclusion Criteria: Prior to paclitaxel and cediranib

1. Patients with a known hypersensitivity to olaparib, cediranib or paclitaxel or any of the excipients of the products
2. Concurrent medical illness that would impact on compliance with the protocol including myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with features suggestive of MDS/AML
3. Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required. Central nervous system metastases:

   1. Symptomatic uncontrolled brain metastases requiring corticosteroid treatment
   2. History of spinal cord compression unless after definitive treatment the patient has clinically stable disease (SD) for at least 28 days prior to starting IMPs. In the absence of these features and in an asymptomatic patient a scan to confirm the absence of brain metastases is not required
4. Known positivity for Hep B, Hep C or HIV
5. Resting ECG with QTc \> 470msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
6. Concomitant use of known strong CYP3A4/5 inhibitors such as such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. Concomitant use of inducers or inhibitors (e.g., phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) is also excluded. The required washout period prior to starting olaparib is 2 weeks
7. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, 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 enzalutamide or phenobarbital and 3 weeks for other agents.
8. Another cancer, which has been active within the previous 5 years, except for 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.
9. Pregnant or lactating. Pregnancy status in women of child bearing potential will be confirmed via a serum or urine pregnancy test prior to randomisation, monthly during the treatment period, and at the end of treatment assessment. In addition, women of child bearing potential MUST be willing to ensure they use effective contraception for four weeks before entering the trial, throughout the treatment period and for six months following the end of treatment. Acceptable methods of contraception are:

   i. true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) ii. a combination of male condom plus one of:
   * vasectomised sexual partner, with participant assurance that partner received post-vasectomy confirmation of azoospermia
   * Tubal occlusion
   * Intrauterine device provided coils are copper-banded
   * Etonogestrel implants (eg, Implanon®, Norplant®)
   * Normal and low dose combined oral pills
   * Hormonal shot or injection (eg, Depo-Provera)
   * Intrauterine system device (eg, levonorgestrel-releasing intrauterine system -Mirena®)
   * Norelgestromin/ethinyl estradiol transdermal system
   * Intravaginal device (eg, ethinyl estradiol and etonogestrel)
   * Cerazette (desogestrel). Cerazette is currently the only highly efficacious progesterone based pill.
10. Patients who are planning to receive maintenance bevacizumab
11. Radiotherapy, surgery or tumour embolization within 28 days before the first dose of cediranib
12. Additional concurrent anti-cancer therapy
13. Malabsorption e.g. uncontrolled diarrhoea or poorly controlled stoma
14. Previous or concurrent leukoencephalopathy, recent (within the past 6 months) arterial thromboembolic event (MI/CVA within previous 6 months), previous or concurrent fistula, previous or concurrent GI perforation, concurrent intra-abdominal abscess, previous VEGF RTKi or clinically relevant proteinuria
15. Inability to comply with the protocol
16. Major surgery within two weeks of starting study treatment and patients must have recovered from any effects of any major surgery
17. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, unstable angina, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, resting ECG with clinically significant abnormal findings, NYHA grade III/IV cardiac failure, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. Left ventricular ejection fraction (LVEF) \< lower limit of normal (LLN) per institutional guidelines, or \<55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors:

    1. Prior treatment with anthracyclines- except liposomal doxorubicin, which is permitted
    2. Prior treatment with trastuzumab
    3. Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT
    4. History of myocardial infarction within 6-12 months prior to start of IMPs
    5. Prior history of other significant impaired cardiac function
18. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
19. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
20. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
21. Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation.

Exclusion Criteria: Prior to switching to olaparib and cediranib

1\. Meet exclusion criteria listed previously as points: 1-7, 9-11, 13-18, 20-21.

• Manchester, United Kingdom