Back to Trials
NCT05659381PHASE3Recruiting

Heated Intraperitoneal Chemotherapy Followed by Niraparib for Ovarian, Primary Peritoneal and Fallopian Tube Cancer

GOG Foundation

Start Date

3/8/2024

Completion Date

8/1/2034

Summary

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).

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Cisplatin

OTHER

No treatment

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Stage III Ovarian CancerStage IV Ovarian CancerStage III Primary Peritoneal CancerStage IV Primary Peritoneal CancerStage III Fallopian Tube CancerStage IV Fallopian Tube Cancer

Locations

City of Hope

Duarte, California 91010

United States

University of California San Diego Moores Cancer Center

La Jolla, California 92037

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Stanford Ambulatory Surgery Center Lane Operating Room

Palo Alto, California 94034

United States

Stanford Women's Cancer Center

Palo Alto, California 94304

United States

Stanford Hospital

Palo Alto, California 94305

United States

University of Colorado Hospital - Anshutz Cancer Pavilion

Aurora, Colorado 80045

United States

Hartford Hospital

Hartford, Connecticut 06102

United States

Smilow Cancer Hospital at Yale- New Haven

New Haven, Connecticut 06511

United States

Yale University School of Medicine

New Haven, Connecticut 06520

United States

Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center

Coral Gables, Florida 33146

United States

University of Miami Hospital and Clinics - Deerfield Beach

Deerfield Beach, Florida 33442

United States

University of Miami Hospital and Clinics

Miami, Florida 33136

United States

Miami Cancer Institute

Miami, Florida 33176

United States

Sylvester Comprehensive Cancer Center - Plantation

Plantation, Florida 33324

United States

University of Kansas Hospital

Kansas City, Kansas 66160

United States

University of Kansas Medical Center MOB

Kansas City, Kansas 66160

United States

University of Kansas Cancer Center Overland Park

Overland Park, Kansas 66210

United States

University of Kansas Indian Creek Breast Surgery

Overland Park, Kansas 66211

United States

University of Kansas Cancer Center Westwood

Westwood, Kansas 66205

United States

University of Kansas Clinical Research Center

Westwood, Kansas 66205

United States

University of Kentucky Medical Center

Lexington, Kentucky 40536

United States

LSU Health New Orleans

New Orleans, Louisiana 70112

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

University of Kansas Cancer Center

Kansas City, Missouri 64116

United States

University of Kansas Cancer Center North

Kansas City, Missouri 64154

United States

University of Kansas Cancer Center Lee's Summit

Lee's Summit, Missouri 64064

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Holy Name Medical Center

Teaneck, New Jersey 07666

United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico 87102

United States

Memorial Sloan-Kettering Cancer Center

New York, New York 10022

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

Duke Women's Cancer Care Raleigh

Raleigh, North Carolina 27607

United States

UH Geauga Medical Center

Chardon, Ohio 44024

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

TriHealth Cancer Institute - Good Samaritan Hospital

Cincinnati, Ohio 45220

United States

TriHealth Cancer Institute- Thomas Comprehensive Care Center

Cincinnati, Ohio 45242

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

SCC at Lake University

Mentor, Ohio 44060

United States

UH Minoff Health Center at Chagrin Highlands

Orange, Ohio 44122

United States

West Chester Hospital

West Chester, Ohio 45069

United States

St. John Medical Center

Westlake, Ohio 44145

United States

Jefferson Abington Hospital

Abington, Pennsylvania 19001

United States

Jefferson Hospital

Jefferson Hills, Pennsylvania 15025

United States

Forbes Hospital

Monroeville, Pennsylvania 15146

United States

West Penn Hospital

Pittsburgh, Pennsylvania 15224

United States

Wexford Hospital

Wexford, Pennsylvania 15090

United States

Asplundh Cancer Pavilion

Willow Grove, Pennsylvania 19090

United States

Lankenau Medical Center/Mainline Medical Center

Wynnewood, Pennsylvania 19096

United States

Medical University of South Carolina (Hollings Cancer Center)

Charleston, South Carolina 29425

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

Texas Oncology - Central South

Austin, Texas 78758

United States

Baylor College of Medicine Medical Center

Houston, Texas 77030

United States

O'Quinn Medical Tower at McNair Campus

Houston, Texas 77054

United States

Inova Schar Cancer Institute

Fairfax, Virginia 22031

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Froedtert Memorial Lutheran Hospital & Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States