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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01226550
First received: October 20, 2010
Last updated: December 28, 2011
Last verified: December 2011
  Purpose

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).


Condition Intervention Phase
Peritoneal Carcinosis (PC)
Procedure: cytoreductive surgery and HIPEC
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Morbidity rate [ Time Frame: 30 days postoperative ] [ Designated as safety issue: Yes ]
    postoperative complications (class III and IV, Common Terminology Criteria V3; National Cancer Institute)


Secondary Outcome Measures:
  • Mortality rate [ Time Frame: 30 days postoperative ] [ Designated as safety issue: Yes ]
  • Intraperitoneal and serumal concentration (pharmacokinetics) of mitomycine C, irinotecan, and its metabolites. [ Time Frame: per-HIPEC ] [ Designated as safety issue: Yes ]
    Plasma, peritoneal, and urinary values for MMC, irinotecan, SN-38, SN-38G, APC, and NPC.


Enrollment: 18
Study Start Date: June 2007
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).


  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01226550

Locations
France
Service de Chirurgie Générale et Thoracique, Centre Hospitalier Lyon-Sud
Pierre Bénite Cedex, France, 69495
Sponsors and Collaborators
Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01226550     History of Changes
Other Study ID Numbers: 2004.368
Study First Received: October 20, 2010
Last Updated: December 28, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
hyperthermic intraoperative peritoneal chemotherapy (HIPEC)
Irinotecan
Pharmacokinetics
peritoneal carcinomatosis (PC)

Additional relevant MeSH terms:
Fever
Body Temperature Changes
Signs and Symptoms
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014