Combined Systemic and Intraperitoneal Chemotherapy for the Treatment of Gastric and/or Gastroesophageal Peritoneal Carcinomatosis

Inclusion Criteria

• Histologically proven, gastric and/or gastroesophageal junction (Siewert 3) adenocarcinoma with synchronous positive peritoneal cytology or macroscopic carcinomatosis (stage IV), diagnosed by imaging or laparoscopy or laparotomy
• Patients must be 18 years of age or older at time of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Note: ECOG performance status (PS) of 2 is allowed only if debilitation is caused by the gastric cancer and not by other comorbidities
• Hemoglobin ≥ 8.0 g/dL (following completion of 4-6 months systemic therapy and prior to enrollment)
• Leukocytes ≥ 3,000/mcL (following completion of 4-6 months systemic therapy and prior to enrollment)
• Absolute neutrophil count ≥ 1,500/mcL (following completion of 4-6 months systemic therapy and prior to enrollment)
• Platelet count ≥ 100,000/mcL (following completion of 4-6 months systemic therapy and prior to enrollment)
• Total bilirubin < 2mg/dl (following completion of 4-6 months systemic therapy and prior to enrollment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 X institutional upper limit of normal (ULN) (following completion of 4-6 months systemic therapy and prior to enrollment)
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X institutional ULN (following completion of 4-6 months systemic therapy and prior to enrollment)
• Serum creatinine within normal institutional limits (following completion of 4-6 months systemic therapy and prior to enrollment)
• Patients should have a life expectancy of > 6 months per the discretion of the treating surgical oncologist and/or medical oncologist in relation to comorbidities and volume of disease
• Patients must have received at least 4 months of effective 1st or 2nd line systemic therapy at the discretion of the treating medical oncologist and/or surgical oncologist and exhibit no evidence of extraperitoneal disease progression prior to enrollment
• Patients with stable oligometastatic liver only metastasis (≤ 3 lesions, each < 3 cm in maximum dimension), ovarian-only metastases, or lung-only metastases (≤ 5 lesions, each < 1 cm) that are amenable to curative intent surgical resection and/or thermal ablation and/or stereotactic body radiation therapy (SBRT) will be eligible for enrollment
• Subjects of reproductive potential and their partners must agree to use dual contraception throughout the study period. This includes one highly effective method (e.g., hormonal contraception, intrauterine device, tubal ligation, or vasectomy) plus one barrier method (e.g., condom with spermicide or diaphragm with spermicide). These measures must be initiated prior to the first study treatment and continued for at least 6 months following the last dose of cisplatin or mitomycin C, given the known genotoxic potential of these agents. Additionally, male participants must agree not to donate sperm and female participants must agree not to donate oocytes during treatment or for 6 months thereafter
• Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: * Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes.) Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff
• Must have the ability to understand and the willingness to sign a written informed consent document
• Must be able to read and write in English

Exclusion Criteria

• Patients with microsatellite instability-high (MSI-H) tumors, mismatch repair deficient (dMMR), tumor mutational burden (TMB) > 30, combined positive score (CPS) > 40, POL-E mutation, Claudin 18.2 positive tumors, BRAFV600E, RET fusions, HER-2-neu (3+ on immunohistochemistry [IHC]) or positive on fluorescence in situ hybridization (FISH) will be excluded
• Extensive retroperitoneal lymph node involvement not amenable to surgical resection during gastrectomy
• Recurrent large or small bowel obstruction, attributable to gastric cancer (except for gastric outlet obstruction)
• Prior abdominal surgeries that preclude safe and effective laparoscopy/laparoscopic HIPEC
• Significant ascites, requiring repeated drainage for symptomatic relief (defined as ≥ 2 therapeutic paracenteses with ascites drainage ≥ 1L each time within 28 days prior to enrollment)
• Other malignancy within the preceding 3 years (except for non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical cancer in-situ)
• Patients should have recovered to baseline from any clinically significant adverse events from prior treatment
• Has acute or chronic active hepatitis B and C virus infection or known history of untreated hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative]) or HIV infection (see note) * Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated * Note: Participants with a history of HIV infection are considered eligible if CD4+ T cell counts are ≥ 350 cells/µL and the patient has had no opportunistic infections in the last 12 months