Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

Study Overview
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Brief Summary
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This is an open, non-randomized, phase I-II, pilot study, which evaluates the combination of optimum cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) with mitomycin C (MMC) and irinotecan. The latter drug will be administered in escalating doses to patients with gastric, colorectal, appendicular, or primary peritoneal carcinosis (PC).

Official Title
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Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

Conditions
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Peritoneal Carcinosis (PC)

Intervention / Treatment
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* Procedure: cytoreductive surgery and HIPEC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a peritoneal carcinosis (PC) either of digestive origin or primary: a colorectal or gastric carcinosis, a peritoneal pseudomyxoma or mesothelioma, or a primary carcinosis of the peritoneum regardless the number of prior treatment lines. A PC and primary tumor considered to be resectable according to preoperative clinical and paraclinical data: absence of mesenteric retraction and absence of bladder invasion. Patients in good general health (ASA ≤ 2). Absence of cardiorespiratory failure (PaO2 > 60 mmHg in a stable condition, dyspnea ≤ NYHA stage 1, left ventricular ejection fraction > 60%.). Prothrombin level >70 %, total bilirubin < 2 x the normal level, ASAT and ALAT < 2.5 x normal levels, and alkaline phosphatases < 5 x normal levels. Creatinine clearance > 60 ml/min, polynuclear neutrophils > 1500/mm3, and a white blood cell count > 4000 /mm3. Patients who give written, informed consent. Patients affiliated with the French universal healthcare system. Exclusion Criteria: Patients with a PC with ovarian, mammary, biliary, pancreatic, or bronchial origin. Evolutive patients after systemic chemotherapy. Patients with a PC considered to be irresectable according to preoperative clinical and paraclinical data: mesenteric retraction or bladder invasion. Patients in poor general health (ASA > 2). Cardiorespiratory failure (dyspnea > NYHA stage 1, PaO2 < 60 mmHg in a stable condition) Prothrombin level < 70 %. Any brain abnormality showing on the head scan. Signs of heart failure and especially left ventricular ejection fraction < 60% on the cardiac ultrasound. Thrombocytopenia < 100 000 / mm3 Visceral metastases other than a single resectable liver metastasis. Pregnancy or breast feeding. Chronic inflammatory intestinal disease and/or an intestinal obstruction. History of severe hypersensitivity to irinotecan hydrochloride trihydrate or one of the excipients of Campto. Bilirubinemia > 3 times the normal upper limit Yellow fever vaccine. Prophylactic treatment with phenytoin. Severe medullary insufficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cytoreductive surgery and HIPEC<br> | Procedure: cytoreductive surgery and HIPEC<br>* The most complete cytoreductive surgery possible (ideally macroscopically complete) followed by a closed-abdomen hyperthermic intraoperative peritoneal chemotherapy (HIPEC), using a closed circuit connected to the self-regulating Cavitherm machine (EEC certified). This perfusion apparatus records temperature, flow, and pressure for 90 minutes at real temperature (42-43°C). The dialysate is made up of peritoneal dialysis fluid containing 0.7 mg/kg of MMC and increasing doses of irinotecan added to the dialysate the last 30 minutes of the HIPEC. Potentiation of irinotecan using an intravenous FUFOL perfusion at least 1hour before HIPEC (1st dose level: 10 mg/m² of folinic acid, then 200 mg/m² of 5-FU; 2nd dose level: 20 mg/m² of folinic acid, then 400 mg/m² of 5-FU).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity rate | postoperative complications (class III and IV, Common Terminology Criteria V3; National Cancer Institute) | 30 days postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate |  | 30 days postoperative | 
| Intraperitoneal and serumal concentration (pharmacokinetics) of mitomycine C, irinotecan, and its metabolites. | Plasma, peritoneal, and urinary values for MMC, irinotecan, SN-38, SN-38G, APC, and NPC. | per-HIPEC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperthermic intraoperative peritoneal chemotherapy (HIPEC), Irinotecan, Pharmacokinetics, peritoneal carcinomatosis (PC)