Heated Chemotherapy and Niraparib for Ovarian Cancer

Inclusion Criteria: 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. Patients must have an ECOG performance status of 0 or 1. 7. Patient must be age \> 18. 8. Patients must have a life expectancy \> 3 months. 9. 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. 10. 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. 11. Patients receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to randomization. 12. Patients must agree to not donate blood during the study or for 90 days after the last dose of study treatment. 13. Patients with known human immunodeficiency virus (HIV) are allowed if they meet all the following criteria: 1. Cluster of differentiation 4 ≥350/µL and viral load \<400 copies/mL 2. No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment 3. No history of HIV associated malignancy for the past 5 years 4. 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 14. Patient or a legally authorized representative must have signed an approved informed consent and authorization permitting the release of personal health information. Exclusion Criteria 1. Patients with low-grade serous, clear cell, mucinous, non-epithelial ovarian cancers and borderline tumors. 2. 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. 3. Patients whose tumors are HRD/LOH negative. 4. 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). 5. Patients not eligible for iCRS based on medical co-morbidities as per the enrolling investigator. 6. Patients with stage IV disease without complete response of extra-abdominal disease on preoperative findings (e.g., pleural effusion, mediastinal, inguinal, supraclavicular lymphadenopathy, mesemchymal liver metastases or other extra-abdominal metastases) who are not deemed resectable with iCRS. 7. Patients with a history of Myelodysplastic Syndrome or Acute Myeloid Leukemia. 8. Patients who are pregnant or lactating. 9. Patients with a severe infection requiring IV antibiotics within 2 weeks of planned randomization. 10. Patients with other uncontrolled, intercurrent medical conditions. 11. Patient with metastatic disease to the central nervous system. 12. Patient with uncontrolled insulin dependent diabetes or pre-existing renal condition. 13. Patients with pre-existing hearing loss related to prior platinum-based chemotherapy. 14. Patients with Prior Reversible Encephalopathy Syndrome (PRES). 15. Patients with current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). Severe hepatic impairment patients should be excluded. 16. Patients with any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels that is not related to ovarian cancer. 17. Patients with clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, uncontrolled cardiac arrhythmia or unstable angina \<6 months to randomization, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident within 6 months). 18. Patients with an increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to study randomization and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months). 19. Patients with known active hepatitis B (eg, hepatitis B surface antigen reactive) are excluded unless their HBV is stably controlled on nucleos(t)ide analogs (eg entecavir or tenofovir) which will be continued for the duration of the study. 20. Patient has had investigational therapy administered within 4 weeks or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to study randomization. 21. Patient has received a live vaccine within 30 days of study randomization. COVID-19 vaccines that do not contain live viruses are allowed at any time during the study. 22. Patient has a diagnosis, detection, or treatment of another type of invasive cancer ≤ 2 years prior to initiating protocol therapy (except for basal or squamous cell carcinoma of the skin, cervical cancer in situ, and ductal cancer in situ (DCIS) that has been definitively treated). 23. Patients must not have had radiotherapy encompassing \> 20% of the bone marrow within 2 weeks of randomization; or any radiation therapy within 1 week prior to randomization.