Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Phase III Study Evaluating the Use of Systemic Chemotherapy and Chemohyperthemia Intraperitoneal Preoperatively (CHIP) and After Maximum Resection of Peritoneal Carcinomatosis Originating With Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00769405
• Other study ID #: CDR0000595024
• Secondary ID: FRE-FNCLCC-ACCOR
• Status: Completed
• Phase: Phase 3
• First received: October 8, 2008
• Last updated: August 29, 2016
• Start date: February 2008

Study information

• Verified date: August 2016
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Française de Sécurité des Aliments et des Produits de Santé
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether systemic chemotherapy is more effective with or without intraperitoneal chemohyperthermia in treating patients with peritoneal carcinomatosis from colorectal cancer.

PURPOSE: This randomized phase III trial is studying systemic chemotherapy to see how well it works compared with or without intraperitoneal chemohyperthermia in treating patients undergoing surgery for peritoneal carcinomatosis from colorectal cancer.

Description:

OBJECTIVES:

Primary

• Compare overall survival of patients with peritoneal carcinoma of colorectal origin undergoing complete surgical resection and receiving systemic chemotherapy with versus without intraperitoneal chemohyperthermia.

Secondary

• Evaluate recurrence-free survival of these patients.

• Evaluate treatment toxicities.

• Determine morbidity from surgical complications.

• Determine prognostic factors of survival.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, residual tumor status (R0/R1 vs R2 ≤ 1 mm), prior regimens of systemic chemotherapy (first vs ≥ second), and preoperative systemic chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo maximal surgical resection of the tumor.

• Arm I: Patients receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and/or after surgery). Patients must stop systemic chemotherapy at least 1 month before receiving intraperitoneal chemohyperthermia (CHIP). If bevacizumab is given as neoadjuvant therapy, then systemic chemotherapy must be discontinued 6 weeks before beginning CHIP. Patients undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes.

• Arm II: Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery).

Tumor markers (ACE and CA 19-9) are assessed at baseline, at 1 month after surgery, and then at follow-up visits.

After completion of study therapy, patients are followed at 1 and 3 months, every 3 months for 3 years, and then every 6 months for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 264
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Peritoneal carcinoma extension = 25 (Sugarbaker Index) (determined intraoperatively)

• Planning to receive standard systemic chemotherapy

• Chemotherapy for metastatic cancer should be initiated 3 months after surgery

• No extraperitoneal metastases, including liver and lung metastasis

• No carcinomatosis of other origin besides colorectal, in particular appendical carcinomatosis

• Macroscopically complete resection (R1) or surgical reduction of tumor to a residual thickness = 1 mm (R2) is possible

PATIENT CHARACTERISTICS:

• WHO performance status 0-1

• Life expectancy > 12 weeks

• ANC = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• AST and ALT = 3 times ULN

• Alkaline phosphatase = 3 times ULN

• Creatinine = 1.25 times ULN

• Eligible for surgery

• No peripheral neuropathy > grade 3

• Not pregnant or nursing

• No other cancer in the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix

• No inability to submit to follow-up medical testing for geographical, social, or psychological reasons

• Affiliated with a social security program

• Not deprived of liberty or under supervision

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemohyperthermia

• No concurrent participation in another study of first-line therapy for this cancer

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Drug:
• fluorouracil
Given IV
• leucovorin calcium
Given IV
• oxaliplatin
Given during surgery

Procedure:
• hyperthermia treatment
Given intraperitoneally during surgery

Locations

Country	Name	City	State
France	Centre Paul Papin	Angers
France	Hôpital Antoine Béclère	Clamart
France	CHU Estaing	Clermont Ferrand
France	Louis Mourier Hospital	Colombes Cedex
France	Hopital Du Bocage	Dijon
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Centre Leon Berard	Lyon
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Regional Rene Gauducheau	Nantes-Saint Herblain
France	Hopital de l'Archet CHU de Nice	Nice
France	Hopital Lariboisiere	Paris
France	Hôpital Lariboisière	Paris
France	Hopital Tenon	Paris
France	Institut Curie	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Institut Jean Godinot	Reims
France	Hopital Universitaire Hautepierre	Strasbourg
France	Centre Hospitalier Regional de Purpan	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		until 3 years	No
Secondary	Recurrence-free survival		until 3 years	No
Secondary	Toxicity by NCI CTCAE v.3.0		until 5 years after surgery	Yes
Secondary	Morbidity from surgical complications (abdominal, extra-abdominal, aplasia)		until 2 months after surgery	Yes