Clinical trial NCT05659381: Heated Intraperitoneal Chemotherapy Followed by Niraparib for Ovarian, Primary Peritoneal and Fallopian Tube Cancer
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 Newly Diagnosed Stage III and IV Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (Heated Ovarian Treatment Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Stage III Primary Peritoneal Cancer
Stage IV Primary Peritoneal Cancer
Stage III Fallopian Tube Cancer
Stage IV Fallopian Tube Cancer
Keywords: HIPEC
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: GlaxoSmithKline
First posted: 2022-12-21
Enrollment: 230
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV 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 A) 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 (Arm B) will receive postoperative standard chemotherapy after recovery from surgery.

Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy (neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing 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 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, stage III or IV documented on CT scan/MRI, must be recommended to undergo neoadjuvant chemotherapy (3-4 cycles allowed) and are considered candidates for interval cytoreductive surgery (iCRS) as determined by the enrolling investigator.
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).
3. Patient must have no gross residual disease or no disease \>1.0 cm in largest diameter following iCRS and prior to randomization.
4. Patients must have Myriad myChoice HRD test results available prior to registration.
5. Patient must have adequate bone marrow and organ function:

   Bone marrow function:

   Hemoglobin ≥ 8.5 g/dL. Absolute neutrophil count (ANC) ≥ 1,000/mm3. Platelets ≥ 100,000/mm3.

   Renal function:

   Creatinine ≤ 1.3mg/dl 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.

   Blood coagulation parameters:

   PT with an INR of ≤ 1.5 and a PTT ≤ 1.5 times the ULN. For patients on full-dose oral anti-coagulation (such as warfarin or rivaroxaban), in-range INR (usually between 2 and 3) and a PTT \<1.2 times the ULN.
6. Patients must have a GOG 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 2 weeks 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 are 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)
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 of 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 randomization
    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 randomization.

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.
3. Patients not eligible for iCRS based on evidence of progression of disease during neoadjuvant chemotherapy (documented on CT scan/MRI required within 28 days of iCRS).
4. Patients not eligible to iCRS based on medical co-morbidites as per enrolling investigator.
5. Patients with stage IV disease without complete response of extra-abdominal disease on preoperative imaging (e.g., pleural effusion, mediastinal, inguinal, supraclavicular lymphadenopathy, or other extra-abdominal metastases) who are not deemed resectable with iCRS.
6. Patients with a history of Myelodysplastic Syndrome or Acute Myeloid Leukemia.
7. Patients who are pregnant or lactating.
8. Patients with a hypersensitivity or allergy to paclitaxel, docetaxel, carboplatin, cisplatin, or niraparib.
9. Patients with a severe infection requiring IV antibiotics within 2 weeks of planned randomization.
10. Patients with other uncontrolled, inter-current medical conditions.
11. Patient with metastatic disease to the central nervous system.
12. Patient with uncontrolled insulin dependent diabetes (HbA1c greater than or equal to 6%) or pre-existing renal condition.
13. Patients with pre-existing hearing loss.
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.
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 prior 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 (e.g., hepatitis B surface antigen reactive) are excluded unless their HBV is stably controlled on nucleos(t)ide analogs (e.g. entecavir or tenofovir) which will be continued for the duration of the study. A patient who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution should be eligible.
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. COVID19 vaccines that do not contain live viruses are allowed at any time during study treatment.
22. Patient has a diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to randomization (except basal or squamous cell carcinoma of the skin and cervical cancer in situ that has been definitively treated)
23. Patients who have had radiotherapy encompassing \> 20% of the bone marrow within 2 weeks of randomization; or any radiation therapy within 1 week prior to randomization.

Primary outcomes:
measure: Progression-free survival
timeFrame: From enrollment until time of disease progression or death, whichever occurs first, or date of last contact if neither progression of death has occured, assessed up to 8 years
Secondary outcomes:
measure: Overall Survival
timeFrame: From enrollment to the time of death or date of last contact, assessed up to 8 years
measure: Frequency and severity of adverse events
timeFrame: Every 28 days up to 3 years
measure: Effect of homologous recombination repair deficiency
timeFrame: 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
measure: Stage of diagnosis at Progression-Free Survival timepont
timeFrame: 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
measure: Stage of diagnosis at Overall Survival timepoint
timeFrame: 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
measure: Residual Disease
timeFrame: At time of surgery
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford Ambulatory Surgery Center Lane Operating Room
state: California
city: Palo Alto
country: United States
facility: Stanford Women's Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anshutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale- New Haven
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Coral Gables
country: United States
facility: Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center
state: Florida
city: Deerfield Beach
country: United States
facility: University of Miami Hospital and Clinics - Deerfield Beach
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Plantation
country: United States
facility: Sylvester Comprehensive Cancer Center - Plantation
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center MOB
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center Overland Park
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Indian Creek Breast Surgery
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center Westwood
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center North
state: Missouri
city: Lee's Summit
country: United States
facility: University of Kansas Cancer Center Lee's Summit
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Raleigh
country: United States
facility: Duke Women's Cancer Care Raleigh
state: North Carolina
city: Chardon
country: United States
facility: UH Geauga Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute - Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute- Thomas Comprehensive Care Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Mentor
country: United States
facility: SCC at Lake University
state: Ohio
city: Orange Village
country: United States
facility: UH Minoff Health Center at Chagrin Highlands
state: Ohio
city: Westlake
country: United States
facility: St. John Medical Center
state: Ohio
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Jefferson Hills
country: United States
facility: Jefferson Hospital
state: Pennsylvania
city: Monroeville
country: United States
facility: Forbes Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Wexford
country: United States
facility: Wexford Hospital
state: Pennsylvania
city: Willow Grove
country: United States
facility: Asplundh Cancer Pavilion
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center/Mainline Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (Hollings Cancer Center)
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology - Central South
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center
state: Texas
city: Houston
country: United States
facility: O'Quinn Medical Tower at McNair Campus
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: GOG Foundation
name: Oliver Zivanovic, MD
role: STUDY_CHAIR
References: