This research study aims to improve the treatment of Peritoneal Carcinomatosis (PC), a condition where cancer spreads within the abdomen. Patients with PC often experience significant pain and nutritional problems. Currently, there isn't a standard treatment approach, and doctors use different combinations of chemotherapy, surgery, and methods to deliver chemotherapy directly into the abdomen (intra-peritoneal or "IP" chemotherapy).

The study will compare two IP chemotherapy methods: HIPEC and PIPAC. HIPEC involves circulating heated chemotherapy through the abdomen during surgery, while PIPAC delivers chemotherapy as a pressurized aerosol during a laparoscopic procedure. Both methods aim to achieve the same goal, but they haven't been directly compared to see which is safer, more tolerable, more effective, and provides better value.

Mitomycin C is the chemotherapy that is being administered but it is not being evaluated in the study. Mitomycin C is an FDA-approved antineoplastic antibiotic, meaning it's a type of chemotherapy drug used to treat cancer. It works by interfering with DNA synthesis, which is essential for cell growth and division. By disrupting DNA, mitomycin C can prevent cancer cells from multiplying and spreading.

The study will enroll up to 200 patients who will be randomly assigned (like the flip of a coin) to receive either HIPEC or PIPAC. Participants will be active on the study for 120-180 days.

During the study, patients will undergo standard diagnostic laparoscopies (a minimally invasive surgical procedure) to assess their eligibility for surgery to remove as much cancer as possible. Before treatment begins, small tissue samples (biopsies) will be taken for analysis in the pathology department. A small portion of this tissue will be saved by the researchers to study the effects of treatment on tumors. Patients will then receive three rounds of chemotherapy administered by either HIPEC or PIPAC, each about six weeks apart, and each during a laparoscopic procedure. Tumor tissue biopsies will be collected at the time of each treatment for analysis in the pathology department, and a small portion of each biopsy will again be saved by the researchers for laboratory work to study the effects of the treatment on tumors.

Finally, patients will have another laparoscopy to assess the treatment's effect and check for any side effects. Although patients will be followed for up to 5 years, no study-specific follow-up visits are required. Participants undergoing this type of treatment also complete quality-of-life surveys at the start of the study, and after each IP chemotherapy treatment, that asks about general health, well-being and ability to do daily activities. Patient responses to these surveys are collected for research purposes.

HIPEC and PIPAC chemotherapy, are already standard ways to treat PC. This means there's no extra risk to study participants. However, as with any treatment, there are some potential risks, such as infection inside the abdomen or injury to organs during the procedure to deliver the chemotherapy. These risks are small and would be the same whether the participant were in the study or receiving these treatments as part of their normal care.

Inclusion Criteria:

1. Males or females age 18 to 80 years.
2. Biopsy-proven or clinically suspected peritoneal carcinomatosis
3. Receipt of at least three months of standard systemic chemotherapy prior with persistence of disease at the time of randomization
4. Not a candidate for surgical cytoreduction at the time of laparoscopy
5. Women at least 18 years of age of childbearing potential must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
6. Must be able to read and understand English and consent for themselves

Exclusion Criteria:

1. Patients who are eligible for definitive cytoreductive surgery at the time of enrollment

2. Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary, or renal disease:

   AST/SGOT > 2.5 times the upper limit of normal ALT/SGPT > 2.5 times the upper limit of normal Total bilirubin > 2.5 times the upper limit of normal Hemoglobin < 7 gm/dL White blood cell count < 3,000/ mm3 Platelet count < 50,000/mm3

3. Any investigational drug use within 30 days prior to enrollment.

4. Systemic therapy within 14 days prior to randomization

5. Allergy or medical contra-indication to chemotherapy utilized in this study

6. Medical contraindication to laparoscopic surgery or complex cytoreductive surgery

7. Pregnant or lactating females.

8. Subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

The treating investigator, participant and care provider will know which procedural arm the participant is assigned to after the enrollment visit has concluded and informed consent has been signed.