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| ID | Type | Description | Link |
|---|---|---|---|
| 217908 | Other Identifier | GSK |
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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIPEC | Experimental | Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Cisplatin 100 mg/m2 IP over 90 minutes at 42 degrees C |
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| No HIPEC | Active Comparator | No treatment |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin | Drug | Cisplatin 100mg/m2 IP over 90 minutes at 42 degrees Celcius |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival stratified by:
| From enrollment to the time of death or date of last contact, assessed up to 8 years |
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Inclusion Criteria:
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:
Patient or a legally authorized representative must have signed an approved informed consent and authorization permitting the release of personal health information.
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sarin Chhab | Contact | 215-854-0770 | schhab@gog.org | |
| Shanon Matkin | Contact | 801-661-1584 | smatkin@gog.org |
| Name | Affiliation | Role |
|---|---|---|
| Leslie Randall, MD | GOG Foundation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Recruiting | Duarte | California | 91010 | United States |
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| No treatment | Other | No treatment with Cisplatin |
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| Frequency and severity of adverse events | The frequency and severity of adverse events as defined by CTCAE version 5.0 | Every 28 days up to 3 years |
| Progression Free Survival | Progression Free Survival stratified by:
| From the time of randomization until the date of first documented disease progression or death from any cause, whichever came first, assessed up to 8 years |
| University of California San Diego Moores Cancer Center | Recruiting | La Jolla | California | 92037 | United States |
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| Hoag Memorial Hospital Presbyterian | Recruiting | Newport Beach | California | 92663 | United States |
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| Stanford Ambulatory Surgery Center Lane Operating Room | Recruiting | Palo Alto | California | 94034 | United States |
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| Stanford Women's Cancer Center | Recruiting | Palo Alto | California | 94304 | United States |
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| Stanford Hospital | Recruiting | Palo Alto | California | 94305 | United States |
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| University of Colorado Hospital - Anshutz Cancer Pavilion | Recruiting | Aurora | Colorado | 80045 | United States |
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| Hartford Hospital | Recruiting | Hartford | Connecticut | 06102 | United States |
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| Smilow Cancer Hospital at Yale- New Haven | Recruiting | New Haven | Connecticut | 06511 | United States |
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| Yale University School of Medicine | Recruiting | New Haven | Connecticut | 06520 | United States |
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| Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center | Recruiting | Coral Gables | Florida | 33146 | United States |
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| University of Miami Hospital and Clinics - Deerfield Beach | Recruiting | Deerfield Beach | Florida | 33442 | United States |
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| University of Miami Hospital and Clinics | Recruiting | Miami | Florida | 33136 | United States |
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| Miami Cancer Institute | Recruiting | Miami | Florida | 33176 | United States |
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| Sylvester Comprehensive Cancer Center - Plantation | Recruiting | Plantation | Florida | 33324 | United States |
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| University of Kansas Hospital | Recruiting | Kansas City | Kansas | 66160 | United States |
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| University of Kansas Medical Center MOB | Recruiting | Kansas City | Kansas | 66160 | United States |
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| University of Kansas Cancer Center Overland Park | Recruiting | Overland Park | Kansas | 66210 | United States |
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| University of Kansas Indian Creek Breast Surgery | Recruiting | Overland Park | Kansas | 66211 | United States |
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| University of Kansas Cancer Center Westwood | Recruiting | Westwood | Kansas | 66205 | United States |
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| University of Kansas Clinical Research Center | Recruiting | Westwood | Kansas | 66205 | United States |
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| University of Kentucky Medical Center | Recruiting | Lexington | Kentucky | 40536 | United States |
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| LSU Health New Orleans | Recruiting | New Orleans | Louisiana | 70112 | United States |
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| University Medical Center New Orleans | Recruiting | New Orleans | Louisiana | 70112 | United States |
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| Mayo Clinic | Recruiting | Rochester | Minnesota | 55905 | United States |
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| University of Kansas Cancer Center | Recruiting | Kansas City | Missouri | 64116 | United States |
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| University of Kansas Cancer Center North | Recruiting | Kansas City | Missouri | 64154 | United States |
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| University of Kansas Cancer Center Lee's Summit | Recruiting | Lee's Summit | Missouri | 64064 | United States |
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| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63110 | United States |
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| Holy Name Medical Center | Recruiting | Teaneck | New Jersey | 07666 | United States |
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| University of New Mexico Comprehensive Cancer Center | Recruiting | Albuquerque | New Mexico | 87102 | United States |
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| Memorial Sloan-Kettering Cancer Center | Recruiting | New York | New York | 10022 | United States |
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| Duke Cancer Center | Recruiting | Durham | North Carolina | 27710 | United States |
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| Duke Women's Cancer Care Raleigh | Recruiting | Raleigh | North Carolina | 27607 | United States |
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| UH Geauga Medical Center | Recruiting | Chardon | Ohio | 44024 | United States |
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| University of Cincinnati Medical Center | Recruiting | Cincinnati | Ohio | 45219 | United States |
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| TriHealth Cancer Institute - Good Samaritan Hospital | Recruiting | Cincinnati | Ohio | 45220 | United States |
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| TriHealth Cancer Institute- Thomas Comprehensive Care Center | Recruiting | Cincinnati | Ohio | 45242 | United States |
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| University Hospitals Cleveland Medical Center | Recruiting | Cleveland | Ohio | 44106 | United States |
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| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
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| SCC at Lake University | Recruiting | Mentor | Ohio | 44060 | United States |
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| UH Minoff Health Center at Chagrin Highlands | Recruiting | Orange | Ohio | 44122 | United States |
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| West Chester Hospital | Recruiting | West Chester | Ohio | 45069 | United States |
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| St. John Medical Center | Recruiting | Westlake | Ohio | 44145 | United States |
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| Jefferson Abington Hospital | Recruiting | Abington | Pennsylvania | 19001 | United States |
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| Jefferson Hospital | Recruiting | Jefferson Hills | Pennsylvania | 15025 | United States |
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| Forbes Hospital | Recruiting | Monroeville | Pennsylvania | 15146 | United States |
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| West Penn Hospital | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
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| Wexford Hospital | Recruiting | Wexford | Pennsylvania | 15090 | United States |
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| Asplundh Cancer Pavilion | Recruiting | Willow Grove | Pennsylvania | 19090 | United States |
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| Lankenau Medical Center/Mainline Medical Center | Recruiting | Wynnewood | Pennsylvania | 19096 | United States |
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| Medical University of South Carolina (Hollings Cancer Center) | Recruiting | Charleston | South Carolina | 29425 | United States |
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| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37232 | United States |
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| Texas Oncology - Central South | Recruiting | Austin | Texas | 78758 | United States |
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| Baylor College of Medicine Medical Center | Recruiting | Houston | Texas | 77030 | United States |
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| O'Quinn Medical Tower at McNair Campus | Recruiting | Houston | Texas | 77054 | United States |
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| Inova Schar Cancer Institute | Recruiting | Fairfax | Virginia | 22031 | United States |
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| Virginia Oncology Associates | Recruiting | Norfolk | Virginia | 23502 | United States |
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| Froedtert Memorial Lutheran Hospital & Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D005185 | Fallopian Tube Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D005184 | Fallopian Tube Diseases |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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