This single-center, Phase 1 dose-escalation study will evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of pressurized intraperitoneal aerosol chemotherapy with mitomycin C (PIPAC-MMC) for patients with unresectable peritoneal carcinomatosis from gastrointestinal primaries (colorectal, high-grade appendiceal, or small bowel). Up to three PIPAC procedures are planned at 8-week intervals while patients continue 5-fluorouracil/leucovorin (5-FU/LV) between procedures. The trial uses a Bayesian optimal interval (BOIN) design to determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Pharmacokinetics (PK), pharmacodynamics (PD), and quality of life (QoL) will be assessed.
Participants must have histologically confirmed peritoneal disease from colorectal, small bowel, or high grade appendiceal adenocarcinoma. High grade appendiceal cancers include moderate or poorly differentiated mucinous or non-mucinous adenocarcinoma, signet ring cell adenocarcinoma, or goblet cell adenocarcinoma. This can be established by image guided biopsy, diagnostic laparoscopy, or previous surgery.
Patients must be ineligible for CRS/HIPEC through one of the following criteria: a) PCI score ≥16. b) Inability to achieve complete cytoreduction due to extent of disease. c) Significant small bowel involvement precluding a complete CRS. d) Unresectable disease in porta hepatis, pelvic side wall or other critical structure. e) Patients who decline invasive cytoreduction.
Participants must be 18 years of age or older.
Participants must have completed at least 4 months of first-line systemic therapy (5-FU based approach with or without biologic therapy).
Participants who have received targeted therapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks for VEGF inhibitors, nitrosoureas or mitomycin C) prior to entering the study.
Participants who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1), except for alopecia and chemotherapy induced peripheral neuropathy < 2.
Patients with extensive metastatic liver disease (>50% liver volume) are excluded from the trial as are patients with brain metastases. Patients with non-peritoneal metastatic disease are otherwise eligible provided they meet the survival expectations of >6 months.
Patients with brain metastases are excluded
Single group
Mitomycin C (MMC)
DrugDelivered intraperitoneally as aerosol under laparoscopy.
Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC)
DeviceA drug delivery approach in which the antineoplastic agent is delivered directly into the peritoneal cavity solution under laparoscopic pressures (12 mm HG).
Maximum Tolerated Dose (MTD)
The MTD of PIPAC-MMC will be determined to establish the recommended phase 2 dose (RP2D).
Event-Free Survival (EFS)
From first PIPAC procedure (Day 1) until the earliest of documented disease progression, onset of bowel-obstruction-related clinical deterioration, death from any cause, or end of study follow-up
Quality of Life
Baseline QofL will be recorded with the European Organization for Research and Treatment of Cancer (EORTC) QLQ Core (QLQ-C30) Questionnaire. The survey will be repeated after each of the PIPAC procedures.
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