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

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).

Study Overview

• Status: Completed
• Conditions: Peritoneal Carcinosis (PC)
• Intervention / Treatment: Procedure: cytoreductive surgery and HIPEC

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Pierre Bénite Cedex, France, 69495
    • Service de Chirurgie Générale et Thoracique, Centre Hospitalier Lyon-Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: cytoreductive surgery and HIPEC

Procedure: cytoreductive surgery and HIPEC; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: October 20, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimate): October 22, 2010

Study Record Updates

• Last Update Posted (Estimate): December 30, 2011
• Last Update Submitted That Met QC Criteria: December 28, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Irinotecan; hyperthermic intraoperative peritoneal chemotherapy (HIPEC); peritoneal carcinomatosis (PC)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Carcinoma; Hyperthermia; Fever
• Other Study ID Numbers: 2004.368