Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer
Condition: Recurrent Platinum Resistant Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Recurrence
Intervention: cediranib and olaparib
Intervention description: Cediranib tablets oral dose 30 mg once daily; Olaparib(Lynparza) tablet 200 mg twice daily
Dose reduction for both products is allowed
Intervention MeSH terms: Olaparib; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: ovarian cancer

Summary:

      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.
    

Eligibility 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 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

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

          2. Previous enrollment in the present study.

          3. Exposure to any IP during the last 4 weeks prior to enrollment.

          4. Previous treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not
             considered as PARPi

          5. 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

          6. Cancer antigen-125 (CA-125) only disease without RECIST 1.1 measurable disease

          7. 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

          8. Clinically significant signs and/or symptoms of bowel obstruction within 3 months
             prior to starting treatment

          9. History of intra-abdominal abscess within 3 months prior to starting treatment

         10. 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

         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