Mass-Based Response Testing to Guide Personalized Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Appendix and Colorectal Cancer in Patients with Peritoneal Metastasis

Inclusion Criteria

• Has histologically confirmed peritoneal metastases with primary diagnosis of American Joint Committee on Cancer (AJCC) 8th Edition stage IV * Appendiceal adenocarcinoma (moderately/poorly differentiated, and/or signet ring cell tumors) * Colorectal adenocarcinoma * Suspected colon, small bowel, or appendiceal adenocarcinoma in setting of unknown primary
• Limited or no extraperitoneal metastases (any of the below) * Any extraperitoneal metastases must be stable and treatable and limited to less than 2 sites and less than 2 lesions
• Has hemoglobin ≥ 8 g/dL (performed within 30 days prior to the first HIPEC)
• Has absolute neutrophil count (ANC) ≥ 1500/uL (performed within 30 days prior to the first HIPEC)
• Has platelet count ≥ 75,000/uL (performed within 30 days prior to the first HIPEC)
• Has total bilirubin ≤ 1.5 times the upper limit of normal (performed within 30 days prior to the first HIPEC)
• Aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (performed within 30 days prior to the first HIPEC)
• Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (performed within 30 days prior to the first HIPEC)
• Has creatinine clearance ≥ 50 mL/min as defined by the Cockcroft-Gault equation (performed within 30 days prior to the first HIPEC)
• Expected survival at the time of first HIPEC is greater than 3 months
• Exhibits unresectable disease (bowel or mesenteric involvement) or Peritoneal Cancer Index > 19
• Adult patient at least 18 years of age at the time of signing informed consent
• Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
• A male participant must agree to use contraception (barrier birth control, abstinence) during the treatment period and for at least 95 days following completion, corresponding to time needed to eliminate any study intervention(s), and refrain from donating sperm during this period
• A female participant of childbearing age is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception (hormonal, barrier birth control, or abstinence). Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
• The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for Foundation for Blood Research. However, the participant may participate in the main study without participating in Foundation for Blood Research (FBR)
• In addition to the criteria above, if a patient has undergone less than 8 cycles of chemotherapy for their metastatic disease at another institution (prior to initial diagnostic laparoscopy) and has not undergone radiation, ablative procedures, or cytoreductive surgery, then they are still eligible to enter the study at the second diagnostic laparoscopy step

Exclusion Criteria

• Has a positive urine pregnancy test within 3 days prior to randomization or treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Note: In the event that 3 days have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study medication
• Has a known allergy to medications used in this study
• Has hypoxia as defined by pulse oximeter reading < 92% at rest or requires intermittent or chronic supplemental oxygen
• No concurrent malignancy that may interfere with the study aims at the discretion of the investigator * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Has known extraperitoneal metastasis aside from the primary tumor
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from treatment initiation, or New York Heart Association Class III or IV congestive heart failure. Medially controlled arrhythmia stable on medication is permitted
• Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥ 150mmHg and/or diastolic blood pressure (DBP) ≥ 90mmHg
• Has moderate to severe hepatic impairment (Child-Pugh B or C)
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (severe dysphasia, bowel obstruction, malabsorption)
• Has progressive disease following the first 3 months of systemic chemotherapy prior to HIPEC who is not in a stable condition to continue with the trial
• Has received radiation, ablative procedures, or cytoreductive surgery to treat metastatic disease within 3 months of initial laparoscopy
• Has an active infection requiring systemic therapy
• Has a known active tuberculosis (TB)/ coronavirus disease (COVID) infection
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention
• Has a known history of poorly controlled HIV infection despite anti-retroviral therapy
• Has a known history of hepatitis B virus (HBV) (defined as hepatitis B virus surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection that is poorly controlled * Note: Testing for HBV and HCV is only required if mandated by the local health authority
• Inability to receive chemotherapy due to medical/insurance reasons
• Requires emergency surgery due to bleeding, perforation, or obstruction
• Has undergone previous iterative intraperitoneal therapy
• Has contraindication to chemotherapy of choice