Intraperitoneal Oxaliplatin in Combo w IV mFOLFIRI for Peritoneal Carcinomatosis From Colorectal & Appendiceal Cancer

Inclusion Criteria:

* Male or female subject aged ≥ 18 years.
* Histopathologically or cytologically confirmed unresectable colon, rectal or appendiceal adenocarcinoma with synchronous or metachronous (defined as occurring \> 6 months after initial diagnosis) peritoneal dissemination of disease. (Stage IV peritoneal-based disease only)
* Patient has active, measurable disease as defined by RECIST 1.1 and assessed by either abdominal CT/MRI.
* Patients must be willing and able as assessed the treating investigator to undergo placement of an IP catheter and a Port-A Cath, if not already present.
* Patients must have known satisfactory cardiopulmonary function as assessed by the treating investigator.
* ECOG Performance Status ≤ 2.
* Adequate organ function as defined as:

  * Hematologic:

    * Absolute neutrophil count (ANC) \> 1200/mm3
    * Platelet count \> 100,000/mm3
  * Hepatic:

    * Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
    * AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN
  * Coagulation:

    * International normalized ratio (INR) ≤ 1.5
    * Patients who are therapeutically anticoagulated and whose antithrombotic treatment can be withheld for operation are eligible.
  * Renal:

    * BUN and serum creatinine within normal limits.
    * eGFR ≥50 mL/min/1.73m2 or creatinine clearance ≥50 mL/min by Cockcroft-Gault
* Negative serum or urine pregnancy test at screening for women of childbearing potential.
* Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last study treatment administration if the risk of conception exists.
* Recovery to baseline or ≤ Grade 1 CTCAE v.5 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
* Willing to return for follow-up.
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

Sensory neuropathy \> grade 1 from prior therapy.

* Known low or absent Dipyrimidine Dehydrogenase (DPD) activity.
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
* Patients with metastases outside the peritoneal cavity.
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

  * Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  * Other clinically significant disorders that would preclude safe study participation.
* Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.

  -Note: Patients on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
* Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.

  -Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy are eligible. Patients with an undetectable HCV viral load on appropriate treatment are eligible.
* Live vaccinations, except flu and COVID within 4 weeks of cycle one day one and while on trial.
* Known prior severe hypersensitivity to platinum compounds, any of the investigational medication or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
* Subjects taking prohibited medications as described in Section 6.4.2. A washout period of prohibited medications for a period of at least 5 half-lives or 4 weeks, whichever is shorter, should occur prior to the start of treatment.