A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation

This is an open label, single arm, multi-center study to assess the efficacy and safety of the combination of cediranib and olaparib tablets in platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma patients who have received at least 3 prior lines of chemotherapy and who do not carry deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutations.
Cancer (Oncology), Cancer (Oncology) - Gynecology
Min Park, MD
Swedish Cancer Institute
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 radiological evidence of disease recurrence within 6 months of the last receipt of platinum-based chemotherapy. Patients with platinum refractory disease are not eligible
  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 e.g. bevacizumab in first line or recurrent setting
  9. At least three prior lines of chemotherapy for advanced ovarian cancer. Only one prior non-platinum treatment is allowed
  10. Confirmation of the availability tumor sample from the primary or recurrent cancer must be provided
  11. Patients must have adequate organ and 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

Exclusion Criteria:

  1. Exposure to any IP during the last 30 days or 5 half-lives (whichever is longer), prior to enrollment
  2. Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPi
  3. Recent cancer-directed therapies: Radiotherapy (RT) within 4 weeks, chemotherapy or other systemic anti-cancer therapy within 4 weeks, or prior anti-angiogenic treatment (e.g., bevacizumab) within 6 weeks prior to starting treatment
  4. Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease
  5. Major surgical procedure within 2 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
  6. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
  7. History of intra-abdominal abscess within 3 months prior to starting treatment
  8. 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
  9. Other malignancy within the last 5 years
  10. Persisting ≥Grade 2 CTCAE toxicity (except alopecia and Grade 2 peripheral neuropathy) from previous anti-cancer treatment(s)
  11. Central nervous system metastases
  12. 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
  13. 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
  14. History of stroke or transient ischemic attack within 6 months
  15. Uncontrolled intercurrent illness
  16. Patients with myelodysplastic syndrome (MDS)/ treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
  17. Concomitant use of known strong and moderated CYP3A4 inhibitors and inducers
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