Trial Comparing Simple Follow-up to Exploratory Laparotomy Plus "in Principle" (Hyperthermic Intraperitoneal Chemotherapy) HIPEC in Colorectal Patients

Multicentric Phase III Trial Comparing Simple Follow-up to Exploratory Laparotomy Plus "in Principle" HIPEC (Hyperthermic Intraperitoneal Chemotherapy) in Colorectal Patients Initially Treated With Surgery and Adjuvant Chemotherapy Who Have a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Multicentric randomised trial. Patients with a high risk of developing colorectal Peritoneal Carcinomatosis (PC) after resection of their primary will be informed, will sign the consent and will be pre-registered. All patients will receive the current standard adjuvant treatment : 6 months of systemic chemotherapy (currently the Folfox-4 regimen which could be modified if the standard is modified). Then a work-up is done to exclude recurrence. The likelihood of a recurrence is low but if this occurs, the patient will not be randomised and will be treated with the best known treatment. If the work-up is negative, patients will be randomised to surveillance alone (control group) or exploratory laparotomy + HIPEC (experimental group).

Inclusion Criteria:

A) Patients presenting with the following history:

1. Histologically-proven colorectal adenocarcinoma

2. Presenting at the time of resection of the primary with one of the following 4 criteria (criteria indicating a high risk of developing PC) :

   • Minimal PC, resected at the same time as the primary
   • Ovarian metastases
   • Rupture of the primary tumour inside the peritoneal cavity,
   • Iatrogenic rupture of the primary tumour during surgery

B) Who have received standard systemic adjuvant chemotherapy (6 months of systemic chemotherapy) :

• Chemotherapy with the Folfox 4 regimen (the current standard treatment ; it can be modified in the future in the two groups, if the standard is modified…).
• Given on an intent-to-treat basis (it can be stopped prematurely for miscellaneous reasons…);

C) Patients who do not present any sign of tumour recurrence at the end of these 6 months of chemotherapy.

D) Patients with the following general characteristics:

1. Age between 18 and 70 years,
2. Performance Status WHO < 2, life expectancy > 12 weeks,
3. Haematological parameters : Polynuclear neutrophils ³ 1.5x109/L, platelets ³ 100x109/L,
4. Liver function : Total Bilirubin £ 1.5 x ULN, AST (SGOT) et ALT (SGPT) £ 3 x ULN, alkaline phosphatases £ 3 x ULN,
5. Renal function : Plasma creatinine £ 1,25 x ULN,
6. Operable patients,
7. Grade £ 2 peripheral neuropathy (CTC AE v3.0 annex 7)
8. Patients entitled to French National Health Insurance coverage.

E)Patients will be informed and a signed consent form will be obtained before initiating any procedure specific to the trial.

Exclusion Criteria:

1. Cancers of non colorectal origin, particularly, appendiceal cancers are excluded
2. Patients presenting with a detectable recurrent tumour
3. Grade ≥ 3 Peripheral neuropathy
4. History of cancer (excepted cutaneous basocellullar cancer or in situ carcinoma of the uterine cervix) with a recurrence during the 5 previous years
5. Patients already included in another trial concerning first-line treatment 6) Pregnant women or likely to be pregnant

7) Persons under guardianship 8) Follow-up impossible for geographic, social or psychological reasons