Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy given per standard institutional guidelines +/- bevacizumab on Day 1 every 21 days for 3-4 cycles. Registered patients who progress during neoadjuvant chemotherapy will not be eligible for iCRS and will be removed from the study.
Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will be performed in the usual fashion in both arms. Patients will be randomized at the time of iCRS (iCRS must achieve no gross residual disease or no disease \>1.0 cm in largest diameter) to receive HIPEC or no HIPEC. Patients randomized to HIPEC Arm will receive a single dose of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery patients will receive standard post-operative platinum-based combination chemotherapy. Patients randomized to surgery only (No HIPEC Arm) will receive postoperative standard chemotherapy after recovery from surgery.
Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy per standard institutional guidelines +/- bevacizumab for a maximum total of 6 cycles of chemotherapy (neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing +/- bevacizumab until progression or 36 months (if no evidence of disease).
Patients must have a pathologic diagnosis of high grade serous or endometroid epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, FIGO stage III or IV documented on CT scan/MRI, must be recommended and agree to undergo platinum-based neoadjuvant chemotherapy with or without physician choice bevacizumab (3-4 cycles allowed, with bevacizumab held for at least 28 days preoperatively) and are considered candidates for (and planned to have) interval cytoreductive surgery (iCRS) followed by chemotherapy and niraparib maintenance as determined by the enrolling investigator. Patients may continue bevacizumab after a minimum of 28 days post iCRS and during niraparib maintenance per local standard.
Patients with stage IV disease must have complete response of extra-abdominal disease on preoperative imaging (e.g. pleural effusion, mediastinal, inguinal, supraclavicular lymphadenopathy, or other extra-abdominal metastases) or be deemed resectable with iCRS.
Patients must have HRD/LOH positive tumors. Patients with germline or somatic BRCA or other similar mutations (RAD51C, RAD51D, BRIP1, BARD) are not required to have HRD/LOH testing. Patients without BRCA or germline mutations must have HRD/LOH testing using Myriad myChoice®/Foundation Medicine/Caris Life Sciences platforms. HRD test results must be available prior to registration to meet entry criteria.
Patients must have R0 (no gross/visible residual disease) or R1 (gross/visible residual disease ≤ 1.0 cm in the longest diameter) following iCRS and prior to randomization.
Patients with low-grade serous, clear cell, mucinous, non-epithelial ovarian cancers and borderline tumors.
Patients who have received prior treatment for ovarian cancer other than the first 3-4 cycles of platinum based neoadjuvant chemotherapy. Prior neoadjuvant treatment with bevacizumab is allowed; bevacizumab must be held for 28 days prior to surgery.
Patients whose tumors are HRD/LOH negative.
Patients not eligible for iCRS based on evidence of progression of disease during neoadjuvant chemotherapy (documented on CT scan/MRI required within 35 days of iCRS).
Parallel
Cisplatin
DrugCisplatin 100mg/m2 IP over 90 minutes at 42 degrees Celcius
No treatment
Other interventionNo treatment with Cisplatin
Progression-free survival
Progression free survival in patients who receive a single treatment of intraoperative HIPEC with cisplatin vs. those who do not receive intraoperative HIPEC with cisplatin.
Overall Survival
Overall survival stratified by: 1. Stage at diagnosis (stage III vs. stage IV) 2. Germline or somatic mutation (yes vs. no) 3. Physician choice bevacizumab (yes vs. no) 4. Residual disease (no gross/visible residual disease vs. gross/visible residual disease less than or equal to 1 cm in longest diameter
Frequency and severity of adverse events
The frequency and severity of adverse events as defined by CTCAE version 5.0
Progression Free Survival
Progression Free Survival stratified by: 1. Stage at diagnosis (stage III vs. stage IV) 2. Germline or somatic mutation (yes vs. no) 3. Physician choice bevacizumab (yes vs. no) 4. Residual disease (no gross/visible residual disease vs. gross/visible residual disease less than or equal to 1 cm in longest diameter
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GOG Foundation
Lead sponsor
GlaxoSmithKline
Collaborator
