Olaparib in Patients With Recurrent Ovarian Cancer Wild Type for Germline and Somatic BRCA 1 and 2 Genes: The MITO 31 Translational Study

Exclusion Criteria

• •1. History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:
• •* stage ≤ IA
• •* no more than superficial myometrial invasion
• •* no lymph vascular invasion
• •* not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma)
• •2. Other malignancy within the last 5 years, except for adequately treated non melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinomna in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for \> 5years
• •3. Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• •4. Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to randomization
• •5. Patients receiving any systemic radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• •6. 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
• •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 (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
• •8. Persistent toxicities \[\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)\] caused by previous cancer therapy, excluding alopecia
• •9. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML
• •10. Patients with symptomatic uncontrolled brain 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
• •11. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• •12. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• •13. Patients considered at 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, 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 disorder that prohibits obtaining informed consent
• •14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• •15. Breast-feeding women
• •16. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
• •17. Patients with a known hypersensitivity to olaparib or any of the excipients of the product
• •18. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
• •19. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• •20. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)
• •21. Any previous treatment with PARP inhibitor, including olaparib
• •22. Involvement in the planning and/ or conduct of the study
• •23. Previous enrolment in the present study