The goal of this clinical trial is to learn if Pressurized intraperitoneal aerosol chemotherapy (PIPAC) significantly improve the progression-free survival (PFS) in patients with advanced peritoneal metastasis from colorectal cancer.

Researchers will compare 2 strategies, systemic treatments (chemotherapy + targeted therapy) corresponding to standard treatment with or without intraperitoneal oxaliplatin (PIPAC) to see if PIPAC improve the progression-free survival.

Participants will:

• receive a standard treatment every 2 weeks for 12 cycles of intravenous FOLFIRI or FOLFIRINOX + targeted systemic therapy (anti-EGFR or anti-VEGF) in the both arms.
• receive up to a maximum of 4 PIPAC every 6 weeks with pressurized aerosol containing oxaliplatin in experimental arm.
• receive a maintenance treatment until progression or until the onset of severe toxicity after 12 cycles.
• be asked to perform a CT scan and carcinoembryonic antigen (CEA) assay every 8 weeks until progression

Inclusion Criteria:

• ECOG performance status of 0 to 2;

• Histopathologically confirmed colonic adenocarcinoma with synchronous or metachronous peritoneal metastasis (PM);

• Unresectable PM defined as any of the following:

  • PCI >15
  • Extended small bowell involvement
  • Poor general condition contra-indication to a major abdominal surgery (eg: a complete cytoreductive surgery), as decided by the medico-surgical team of the investigator's site specialised in peritoneal carcinomatosis in charge of the patient.

• A surgical exploration performed less than 4 weeks before inclusion (if not, a laparoscopic exploration must be performed);

• First line systemic chemotherapy for advanced / metastatic colonic adenocarcinoma. Systemic chemotherapy in an adjuvant setting is allowed if completed more than 6 months before recurrence and without persistent oxaliplatin-induced neuropathy;

• No extended intraperitoneal adherences defined by at least 9 out of 13 abdominal regions correctly explored during surgical exploration (laparoscopy or laparotomy;

Exclusion Criteria:

• Other cancer treated within the last 3 years, with the exception of in situ cervical carcinoma or basocellular carcinoma;
• Rectal cancer primary (tumor <15 cm from the anal verge);
• Mutational status corresponding to microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR);
• Complete or partial bowel obstruction unresponsive to medical treatment;
• Extraperitoneal polymetastatic diseases. (Only oligometastatic1 diseases are allowed for inclusion);
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months prior to enrolment;
• Active gastrointestinal bleeding;
• Inflammatory bowel disease;
• Peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0, grade ≥2