University of Kansas Medical Center

• Ability to understand and the willingness to sign a written informed consent. - Peritoneal Surface Disease (PSD) due to Colorectal Cancer or High-Grade Appendiceal Cancer - No clear evidence of systemic metastases - No prior CRS-HIPEC treatment - Patient has a planned CC0 (Complete Macroscopic Cytoreduction (visual)) cytoreduction - NOTE: randomization occurs during surgery and not before; if, during surgery, the PI/SubI discerns that all disease cannot be removed surgically, the participant will be considered a "screen failure", HIPEC will not be performed, and the participant will be removed from the study. If participant is removed from the study, PI / surgeon will decide if standard of care surgery will proceed. - Age 18 - 75 - ECOG (Eastern Cooperative Oncology Group) Score 0 - 2 - Recorded ASA (American Society of Anesthesiologist Classification) classification - as determined by the anesthesiologist (particular value not required - only recording of the classification is required). - Medically fit to undergo complex major abdominal surgery, as determined by examination by PI / Sub-Is. - Medically fit to receive systemic chemotherapy, as determined by examination by PI / Sub-Is. - Adequate organ and marrow function as defined below: - leukocytes ≥ 3,000/mcL (microliter) - absolute neutrophil count ≥ 1,500/mcL - platelets ≥ 100,000/mcL - total bilirubin within normal institutional limits - AST (Aspartate aminotransferase) (SGOT [Serum Glutamic Oxaloacetic Transaminase]) ≤ 2.5 X institutional upper limit of normal - ALT (Alanine Aminotransferase) (SPGT [Serum Glutamic Pyruvic Transaminase]) ≤ 2.5 X institutional upper limit of normal - creatinine within normal institutional limits - Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. - A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: - Has not undergone a hysterectomy or bilateral oophorectomy; or - Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) - Men of child-bearing potential must not donate sperm while on this study and for 90 days after the study treatment (surgery with HIPEC).

Participants meeting any of the exclusion criteria at baseline will be excluded from study participation. - Current or anticipated use of other investigational agents while participating in this study. - Patient has received systemic chemotherapy or radiotherapy within 4 weeks prior to study enrollment. - Patient has not recovered sufficiently (PI will judge patient recovery status) from adverse events due to agents administered more than 4 weeks prior to enrollment on this study. - Patient has history of or currently has non-peritoneal surface metastatic disease in addition to peritoneal surface malignancy. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to mitomycin-C or melphalan. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, life-threatening cardiac arrhythmia, severe pulmonary disease, uncontrolled diabetes, severe kidney disease or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants. - Patient actively being treated for other malignancy (current active treatment of early stage squamous or basal cell carcinomas of the skin is allowed, excluding treatment with other investigational agents and systemic chemotherapy or radiotherapy).