MITO 35a: Olaparib Maintenance Therapy in Newly Diagnosed BRCA Wild-type Advanced Ovarian, Fallopian Tube and Primitive Peritoneal Cancer

Exclusion Criteria

• •1. Patients have received Bevacizumab in concomitance with first line platinum-based therapy.
• •2. Clear cell, mucinous and mixed mullerian tumors/carcinosarcoma, non-epithelial tumors or ovarian tumors with low malignant potential (ie. borderline tumors) are not allowed.
• •3. Received chemotherapy within 14 days to first dose to study drug and / or persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 grade 2) caused by previous cancer therapy, excluding alopecia, peripheral neuropathy and related effects of prior chemotherapy that are unlikely to be exacerbated by treatment with study drug.
• •4. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
• •5. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).
• •6. Breast feeding women.
• •7. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• •8. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection \[Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, New York Heart Association (NYHA) grade II or greater congestive heart failure, uncontrolled hypertension, severe peripheral vascular disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric illness \]
• •9. Patients with active second malignancy.
• •10. 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.
• •11. Any prior treatment for ovarian cancer, other than first line platinum-based therapy, including any maintenance treatment between completion of the platinum regimen and initiation of study drug in this study.
• •12. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• •13. Concurrent treatment with other investigational agents.
• •14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• •15. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, eg. Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
• •16. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• •17. Patients with symptomatic uncontrolled brain metastases. A TC/RMN scan of brain is required at baseline. 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.
• •18. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• •19. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \< 470 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• •20. Evidence of any other medical conditions, physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications;
• •21. 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.
• •22. Concomitant use of known strong (e.g. 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.
• •23. Patients with a known hypersensitivity to olaparib or any of the excipients of the product;
• •24. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and in the opinion of the investigator, would make the