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

NCT05659381 · GOG Foundation
In plain English

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Official title
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)
About this study
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
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.
Study design
Enrollment target: 220 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-03-08
Estimated completion: 2034-08-01
Last updated: 2026-04-16
Interventions
Drug: CisplatinOther: No treatment
Primary outcomes
  • Progression-free survival (From enrollment until time of disease progression or death, whichever occurs first, or date of last contact if neither progression of death has occurred, assessed up to 8 years)
Sponsor
GOG Foundation · network
With: GlaxoSmithKline
Contacts & investigators
ContactSarin Chhab · contact · schhab@gog.org · 215-854-0770
ContactShanon Matkin · contact · smatkin@gog.org · 801-661-1584
InvestigatorLeslie Randall, MD · study_chair, GOG Foundation
All locations (59)
City of HopeRecruiting
Duarte, California, United States
University of California San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
Hoag Memorial Hospital PresbyterianRecruiting
Newport Beach, California, United States
Stanford Ambulatory Surgery Center Lane Operating RoomRecruiting
Palo Alto, California, United States
Stanford Women's Cancer CenterRecruiting
Palo Alto, California, United States
Stanford HospitalRecruiting
Palo Alto, California, United States
University of Colorado Hospital - Anshutz Cancer PavilionRecruiting
Aurora, Colorado, United States
Hartford HospitalRecruiting
Hartford, Connecticut, United States
Smilow Cancer Hospital at Yale- New HavenRecruiting
New Haven, Connecticut, United States
Yale University School of MedicineRecruiting
New Haven, Connecticut, United States
Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical CenterRecruiting
Coral Gables, Florida, United States
University of Miami Hospital and Clinics - Deerfield BeachRecruiting
Deerfield Beach, Florida, United States
University of Miami Hospital and ClinicsRecruiting
Miami, Florida, United States
Miami Cancer InstituteRecruiting
Miami, Florida, United States
Sylvester Comprehensive Cancer Center - PlantationRecruiting
Plantation, Florida, United States
University of Kansas HospitalRecruiting
Kansas City, Kansas, United States
University of Kansas Medical Center MOBRecruiting
Kansas City, Kansas, United States
University of Kansas Cancer Center Overland ParkRecruiting
Overland Park, Kansas, United States
University of Kansas Indian Creek Breast SurgeryRecruiting
Overland Park, Kansas, United States
University of Kansas Cancer Center WestwoodRecruiting
Westwood, Kansas, United States
University of Kansas Clinical Research CenterRecruiting
Westwood, Kansas, United States
University of Kentucky Medical CenterRecruiting
Lexington, Kentucky, United States
LSU Health New OrleansRecruiting
New Orleans, Louisiana, United States
University Medical Center New OrleansRecruiting
New Orleans, Louisiana, United States
Mayo ClinicRecruiting
Rochester, Minnesota, United States
University of Kansas Cancer CenterRecruiting
Kansas City, Missouri, United States
University of Kansas Cancer Center NorthRecruiting
Kansas City, Missouri, United States
University of Kansas Cancer Center Lee's SummitRecruiting
Lee's Summit, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Holy Name Medical CenterRecruiting
Teaneck, New Jersey, United States
University of New Mexico Comprehensive Cancer CenterRecruiting
Albuquerque, New Mexico, United States
Memorial Sloan-Kettering Cancer CenterRecruiting
New York, New York, United States
Duke Cancer CenterRecruiting
Durham, North Carolina, United States
Duke Women's Cancer Care RaleighRecruiting
Raleigh, North Carolina, United States
UH Geauga Medical CenterRecruiting
Chardon, Ohio, United States
University of Cincinnati Medical CenterRecruiting
Cincinnati, Ohio, United States
TriHealth Cancer Institute - Good Samaritan HospitalRecruiting
Cincinnati, Ohio, United States
TriHealth Cancer Institute- Thomas Comprehensive Care CenterRecruiting
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical CenterRecruiting
Cleveland, Ohio, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
SCC at Lake UniversityRecruiting
Mentor, Ohio, United States
UH Minoff Health Center at Chagrin HighlandsRecruiting
Orange, Ohio, United States
West Chester HospitalRecruiting
West Chester, Ohio, United States
St. John Medical CenterRecruiting
Westlake, Ohio, United States
Jefferson Abington HospitalRecruiting
Abington, Pennsylvania, United States
Jefferson HospitalRecruiting
Jefferson Hills, Pennsylvania, United States
Forbes HospitalRecruiting
Monroeville, Pennsylvania, United States
West Penn HospitalRecruiting
Pittsburgh, Pennsylvania, United States
Wexford HospitalRecruiting
Wexford, Pennsylvania, United States
Asplundh Cancer PavilionRecruiting
Willow Grove, Pennsylvania, United States
Lankenau Medical Center/Mainline Medical CenterRecruiting
Wynnewood, Pennsylvania, United States
Medical University of South Carolina (Hollings Cancer Center)Recruiting
Charleston, South Carolina, United States
Vanderbilt University Medical CenterRecruiting
Nashville, Tennessee, United States
Texas Oncology - Central SouthRecruiting
Austin, Texas, United States
Baylor College of Medicine Medical CenterRecruiting
Houston, Texas, United States
O'Quinn Medical Tower at McNair CampusRecruiting
Houston, Texas, United States
Inova Schar Cancer InstituteRecruiting
Fairfax, Virginia, United States
Virginia Oncology AssociatesRecruiting
Norfolk, Virginia, United States
Froedtert Memorial Lutheran Hospital & Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States