Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer

Inclusion Criteria

• •1. Ability and willingness to provide written informed consent, and to comply with the requirements of the protocol
• •2. Females aged ≥18 years with previous histologically proven diagnosis of high grade serous, high grade endometroid or clear cell ovarian cancer, fallopian tube or primary peritoneal carcinoma
• •3. No evidence of deleterious or suspected deleterious germline mutation in BRCA1 or BRCA2 genes
• •4. Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy
• •5. CT/MRI evidence of measurable disease as per RECIST 1.1 defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) and which is suitable for accurate repeated measurements
• •6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• •7. Life expectancy ≥12 weeks
• •8. Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
• •9. At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol
• •10. Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided
• •11. Patients must have adequate organ and bone marrow function
• •12. Adequately controlled blood pressure
• •13. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
• •14. Able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
• •15. Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of IPs
• •11. Other malignancy within the last 5 years
• •12. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
• •13. Central nervous system metastases
• •14. Patients with any of the following: History of myocardial infarction within 6 months prior to starting treatment; Unstable angina; Resting electrocardiogram (ECG) with clinically significant abnormal findings; New York Heart Association functional classification of III or IV
• •15. 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: Prior treatment with anthracyclines; Prior treatment with trastuzumab; Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT; History of myocardial infarction within 6-12 months prior to start of IPs; Prior history of other significant impaired cardiac function
• •16. History of stroke or transient ischemic attack within 6 months
• •17. Uncontrolled intercurrent illness
• •18. Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
• •19. No prior allogenic bone marrow transplant or double umbilical cord blood transplantation
• •20. Known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection on antiviral treatment
• •21. Concomitant use of known strong or moderate CYP3A inhibitors
• •22. Concomitant use of known strong or moderate CYP3A inducers