A Randomized Phase II/III Study of the Combination of Cediranib and Olaparib Compared to Cediranib or Olaparib Alone, or Standard of Care Chemotherapy in Women with Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal
- Conditions
- Neoplasms
- Registration Number
- KCT0004526
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 350
3.1.1Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either serous or endometrioid cancer based on local histopathological findings. Both endometrioid and serous histology should be high-grade for eligibility of non-mutation carriers.
Patients with clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory.
3.1.2Patients should have recurrent platinum-resistant or- refractory disease
3.1.4 evaluable disease
3.1.5Prior therapy:
3.1.5.1No more than 3 prior treatment regimens
3.1.5.2Patients may not have had a prior anti-angiogenic agent in the recurrent setting.
3.1.5.3Patients may not have previously received a PARP-inhibitor.
3.1.6Patient must have provided study specific informed consent prior to study entry.
3.1.7ECOG performance status 0 or 1 or 2.
3.1.8Patients must have adequate organ and marrow function as defined below
•Absolute neutrophil count > 1,500/mcL
•Platelets > 100,000/mcL
•Hemoglobin > 10 g/dL
•Total bilirubin < 1.5 times the upper limit of normal (ULN) institutional limits
•AST (SGOT)/ALT (SGPT) < 3 × institutional ULN. If intrahepatic liver metastases are present, AST and ALT must be = 5 times institutional ULN.
•Creatinine < 1.5 X the institutional ULN
•Urine protein: creatinine ratio (UPC) of =1 OR less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have a 24-hour urine collection demonstrating protein of = 500mg over 24 hours.
3.1.9Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to Grade 1 as per CTCAE .
Patients with long-standing stable grade 2 neuropathy may be considered after discussion with the Study Chair.
3.1.10Adequately controlled blood pressure (SBP =140; DBP = 90mmHg) on maximum of three antihypertensive medications.
3.1.11Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and TSH within normal limits.
3.1.12Able to swallow and retain oral medications and without GI illnesses that would preclude absorption of cediranib or olaparib.
3.1.13Age = 18 years
3.1.14 women of child-bearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to use two reliable forms of contraception
3.2.1Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of starting treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not have had hormonal therapy within 2 weeks prior to entering the study.
3.2.2Any other investigational agents within the past 4 weeks.
3.2.3Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib.
3.2.4Prior use of PARP-inhibitors.
3.2.5CA-125 only disease without RECIST 1.1 measurable or otherwise evaluable disease.
3.2.6Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib.
3.2.7Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
3.2.8History of intra-abdominal abscess within the past 3 months.
3.2.9History of gastrointestinal perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula. (12/05/2016)
3.2.10Dependency on IV hydration or TPN.
3.2.11Any concomitant or prior invasive malignancies with the following curatively treated exceptions:
3.2.11.1Treated limited stage basal cell or squamous cell carcinoma of the skin.
3.2.11.2Carcinoma in situ of the breast or cervix.
3.2.11.3Primary endometrial cancer meeting the following conditions: Stage not greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous/serous, clear cell, or other FIGO grade 3 lesions. (12/05/2016)
3.2.11.4Prior cancer treated with a curative intent with no evidence of recurrent disease 5 years following diagnosis and judged by the investigator to be at low risk of recurrence.
3.2.12Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on CT or MRI scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events. Patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study drug.
3.2.13Patients with any of the following:
3.2.13.1History of myocardial infarction within six months
3.2.13.2Unstable angina
3.2.13.3Resting ECG with clinically significant abnormal findings.
3.2.13.4New York Heart Association functional classification of III or IV
.
3.2.14If cardiac function assessment is clinically indicated or performed: LVEF less than normal per institutional guidelines, or <55%, if threshold for normal not otherwise specified by institutional guidelines.
3.2.15History of stroke or transient ischemic attack within six months
3.2.16Clinical significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
3.2.17Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method overall survival
- Secondary Outcome Measures
Name Time Method Progression-free survival;Quality of Life;Adverse Events