Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan
Primary Purpose
Peritoneal Carcinosis (PC)
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
cytoreductive surgery and HIPEC
Sponsored by
About this trial
This is an interventional treatment trial for Peritoneal Carcinosis (PC) focused on measuring hyperthermic intraoperative peritoneal chemotherapy (HIPEC), Irinotecan, Pharmacokinetics, peritoneal carcinomatosis (PC)
Eligibility 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.
Sites / Locations
- Service de Chirurgie Générale et Thoracique, Centre Hospitalier Lyon-Sud
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
cytoreductive surgery and HIPEC
Arm Description
Outcomes
Primary Outcome Measures
Morbidity rate
postoperative complications (class III and IV, Common Terminology Criteria V3; National Cancer Institute)
Secondary Outcome Measures
Mortality rate
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.
Full Information
NCT ID
NCT01226550
First Posted
October 20, 2010
Last Updated
December 28, 2011
Sponsor
Hospices Civils de Lyon
1. Study Identification
Unique Protocol Identification Number
NCT01226550
Brief Title
Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan
Official Title
Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan
Study Type
Interventional
2. Study Status
Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Carcinosis (PC)
Keywords
hyperthermic intraoperative peritoneal chemotherapy (HIPEC), Irinotecan, Pharmacokinetics, peritoneal carcinomatosis (PC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
cytoreductive surgery and HIPEC
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
cytoreductive surgery and HIPEC
Intervention Description
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).
Primary Outcome Measure Information:
Title
Morbidity rate
Description
postoperative complications (class III and IV, Common Terminology Criteria V3; National Cancer Institute)
Time Frame
30 days postoperative
Secondary Outcome Measure Information:
Title
Mortality rate
Time Frame
30 days postoperative
Title
Intraperitoneal and serumal concentration (pharmacokinetics) of mitomycine C, irinotecan, and its metabolites.
Description
Plasma, peritoneal, and urinary values for MMC, irinotecan, SN-38, SN-38G, APC, and NPC.
Time Frame
per-HIPEC
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Service de Chirurgie Générale et Thoracique, Centre Hospitalier Lyon-Sud
City
Pierre Bénite Cedex
ZIP/Postal Code
69495
Country
France
12. IPD Sharing Statement
Learn more about this trial
Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan
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