NRG-GY005

• Patients 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 should have recurrent platinum-resistant or- refractory disease - defined as disease that has progressed by imaging while receiving platinum or had recurrence within 6 months of the last receipt of platinum-based chemotherapy.
• Phase II study: measurable disease by RECIST 1.1 criteria. If archival tumor sample is not available tumor sample from fresh biopsy is acceptable.
• Phase III study: evaluable disease – defined as RECIST 1.1 measurable disease OR nonmeasurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 > 2x ULN).
• Age ≥ 18 years.
• ECOG performance status 0 or 1 or 2

Ineligibility Criteria

• Patients 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.
• Any other investigational agents within the past 4 weeks.
• Prior use of PARP-inhibitors
• Any concomitant or prior invasive malignancies with the following curatively treated exceptions: Treated limited stage basal cell or squamous cell carcinoma of the skin, Carcinoma in situ of the breast or cervix.
• Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on CT or MRI scans.
• Known HIV-positive individuals are ineligible.

Treatment

PHASE II: Patients are randomized to 1 of 4 treatment arms.

     ARM I (REFERENCE REGIMEN): Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel intravenously (IV) on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity.

     ARM II (CEDIRANIB MALEATE AND OLAPARIB): Patients receive cediranib maleate orally (PO) and olaparib PO as determined from an ongoing Phase I study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     ARM III (CEDIRANIB): Patients receive cediranib maleate PO daily continuously. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     ARM IV (OLAPARIB): Patients receive olaparib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE III: Patients are randomized to 1 of 3 treatment arms.

     ARM I (REFERENCE REGIMEN): Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I.

     ARM II (CEDIRANIB AND OLAPARIB): Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II.

     ARM III (SINGLE AGENT): Patients receive either olaparib maleate PO or cediranib PO, as determined by the Phase II study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.

https://clinicaltrials.gov/ct2/show/NCT02502266

Study status is:
Suspended (Scheduled Interim Monitoring) - The study has stopped early but may start again.