IRB Study Number 23-1180
Status Recruiting
Institute Taussig Cancer Institute
Description
2.1 Primary Objective
• To determine if a single treatment with intraoperative HIPEC with cisplatin (treatment arm) at the time of optimal iCRS will result in improved PFS as compared to optimal iCRS alone (standard arm) in patients with stage III or IV (pleural effusion only) EOC who are treated with neoadjuvant IV platinum-based chemotherapy followed by niraparib maintenance.
2.2 Secondary Objectives
• To assess overall survival (OS).
• To assess the frequency and severity of adverse events as defined by CTCAE version 5.0.
• To assess the effect of homologous recombination repair deficiency (HRD) (yes or no), as defined by standard of care Myriad myChoiceâ HRD test, on PFS and OS.
• To assess the effect of stage at diagnosis (III or IV) on PFS and OS.
• To assess the effect of residual disease (no visible residual vs residual disease present) on PFS and OS.
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 to undergo neoadjuvant chemotherapy (3-4 cycles allowed) and are considered candidates for (and planned to have) interval cytoreductive surgery (iCRS) as determine by the enrolling investigator.
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 deemed resectable with iCRS.
Patient must have no gross residual disease or no disease >1.0 cm in largest diameter.
Patients must have Myriad myChoiceâ HRD test results available prior to registration.
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 ≤ 2.5 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.
Patients must have a GOG 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 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 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).
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 of the following criteria:
a. Cluster of differentiation 4 ≥350/μL and viral load <400 copies/mL
b. No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
c. No history of HIV associated malignancy for the past 5 years
d. 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
- Patient or a legally authorized representative must have signed an approved informed consent and authorization permitting the release of personal health information.
Exclusion Criteria
Patients with low-grade serous, clear cell, mucinous, non-epithelial ovarian cancers and borderline tumors.
Patients who have received prior treatment for ovarian cancer other than the first 3-4 cycles of platinum based neoadjuvant chemotherapy.
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).
Patients not eligible for iCRS based on medical co-morbidities as per the enrolling investigator.
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.
Patients with a history of Myelodysplastic Syndrome or Acute Myeloid Leukemia.
Patients who are pregnant or lactating.
Patients with a hypersensitivity or allergy to paclitaxel, docetaxel, carboplatin, cisplatin, or niraparib.
Patients with a severe infection requiring IV antibiotics within 2 weeks of planned randomization.
Patients with other uncontrolled, inter-current medical conditions.
Patient with metastatic disease to the central nervous system.
Patient with uncontrolled insulin dependent diabetes (HbA1c ³ 6%) or pre-existing renal condition.
Patients with pre-existing hearing loss.
Patients with Prior Reversible Encephalopathy Syndrome (PRES).
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.
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.
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).
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).
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.
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.
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.
Patient has a diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer in situ that has been definitively treated)
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.
