Study Evaluating the Efficacy of Maintenance Olaparib and Cediranib or Olaparib Alone in Ovarian Cancer Patients.

Exclusion Criteria34

• Non-epithelial ovarian cancer, carcinosarcoma, clear cell carcinoma and mucinous carcinomas.
• Arterial thrombotic event (including transient ischaemic attack, cerebrovascular accident, and peripheral arterial embolus) within the last 12 months.
• Patients unable to swallow orally administered medication and patients with gastrointestinal impairment that could affect ability to take, or absorption of oral medicines including sub-acute or complete bowel obstruction.
• Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment.
• History of intra-abdominal abscess within 3 months prior to starting treatment.
• History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula.
• Symptomatic or clinically significant inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
• Patients with an ileostomy will be excluded.
• Evidence of severe or uncontrolled cardiac disease.
• a. Myocardial infarct or unstable angina within the last 6 months
• b. New York Health Association (NYHA) equal to or greater than grade 2 congestive heart failure
• c. Cardiac ventricular arrhythmias requiring medication
• d. History of 2nd or 3rd degree atrioventricular conduction defects
• Resting ECG with QTcF greater than 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Evidence of active bleeding or bleeding diathesis.
• Significant haemorrhage of greater than 30ml in a single episode within the last 3 months or any haemoptysis (greater than 5ml fresh blood in last 4 weeks).
• Malignancy treated within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage 1, grade 1 endometrial carcinoma.
• Previous treatment with VEGFR tyrosine kinase inhibitors or PARP inhibitors are not permitted.
• Patients with a known hypersensitivity to excipients of cediranib or olaparib
• Persisting equal to or greater than grade 2 CTCAE toxicity (except alopecia and neuropathy) from previous anti-cancer treatment.
• Major surgery within 14 days before anticipated start of treatment and patients must have recovered from any effects of major surgery.
• Inability to attend or comply with treatment or follow-up scheduling.
• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicated the use of an investigation drug or puts the patients at high risk for treatment-related complications.
• Pregnant or breast-feeding women are excluded. Women of childbearing potential will be excluded unless effective methods of contraception are used from signing of the informed consent, throughout the period of taking study treatment and for at least 6 weeks after last dose of trial drug(s).
• Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
• Concomitant use of known CYP3A4 inhibitors (such as ketoconazole, itraconazole, protease inhibitors boosted with ritonavir or cobicastat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir, telithromycin and clarithromycin or moderate CYP3A inhibitors (e.g. Ciprofloxacin, erthromycicn, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• 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.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia.
• Other psychological, psychiatric, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
• Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
• Immunocompromised patients e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
• Patients with symptomatic uncontrolled brain or meningeal metastases. A scan to confirm the absence of brain metastases is not required. 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 for 28 days.
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).