GOG-3068: A Phase III Randomized Trial of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Cisplatin Versus no HIPEC at the Time of Optimal Interval Cytoreductive Surgery Followed by Niraparib Maintenance in Patients With Homologous Recombinant Deficient (HRD +) Newly Diagnosed Stage III and IV Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (Heated Ovarian Treatment Trial)
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.
• Patient must have adequate bone marrow and organ function:
• Bone marrow function:
• Hemoglobin ≥ 8.5 g/dL. Absolute neutrophil count (ANC) ≥ 1,500/mm3. Platelets ≥ 100,000/mm3.
• Renal function:
• Creatinine ≤ 1.3mg/dl OR Calculated creatinine clearance (≥ 30 mL/min/1.73 m2) per National Kidney Foundation guidelines and NHANES III
• Hepatic function:
• Bilirubin ≤ 1.5 times ULN. ALT ≤ 3 times the ULN. AST ≤ 3 times the ULN.
• Neurologic function:
• Peripheral neuropathy ≤ CTC AE grade 2.
• Patients must have an ECOG performance status of 0 or 1.
• Patient must be age \> 18.
• Patients must have a life expectancy \> 3 months.
• Patients of childbearing potential must have a negative serum pregnancy test within 28 days prior to iCRS and must be practicing an effective form of contraception (with failure rate \<1% per year) during the study period and for 6 months following the last dose of niraparib. Patients of childbearing potential must consent to pregnancy testing prior to receiving niraparib and monthly thereafter for the duration of the study.
• Patients are considered postmenopausal and not of child-bearing potential if they are free from menses for \>1 year or surgically sterilized.
⁃ Patients must have normal blood pressure (BP) or adequately treated and controlled hypertension based on local standard of care (systolic BP ≤ 140 mmHg and diastolic ≤ 90 mmHg) prior to starting niraparib.
⁃ Patients receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to randomization.
⁃ Patients must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
⁃ Patients with known human immunodeficiency virus (HIV) are allowed if they meet all the following criteria:
∙ Cluster of differentiation 4 ≥350/µL and viral load \<400 copies/mL
‣ No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
‣ No history of HIV associated malignancy for the past 5 years
‣ Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started \>4 weeks prior to study enrollment
⁃ Patient or a legally authorized representative must have signed an approved informed consent and authorization permitting the release of personal health information.