Combination Chemotherapy With or Without Irinotecan in Treating Patients With Stage III Colon Cancer

Phase III Randomized Study of Intensive Adjuvant Chemotherapy for Resected Colon Cancer at High Risk of Recurrence

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without irinotecan in treating colon cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without irinotecan in treating patients who have stage III colon cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: FOLFIRI regimen

Detailed Description

OBJECTIVES:

• Compare the effect of leucovorin calcium and fluorouracil with or without irinotecan on the 3 year survival rate and overall survival of patients with resected node positive colon cancer at high risk of recurrence.
• Compare toxicities of these regimens in these patients.
• Compare quality of life of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, disease type (occlusion vs perforation vs N2 only), delay between surgery and chemotherapy (28 days or less vs over 28 days), and age (under 65 vs 65 and over). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2.
• Arm II: Patients receive irinotecan IV over 90 minutes on day 1 followed by leucovorin calcium and fluorouracil as in arm I.

Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before treatment, after 6 and 12 courses, and then at 1 year.

Patients are followed every 3 months for 2 years, then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 400 patients (200 per arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49036
    • Centre Paul Papin
  • Bayonne, France, 64100
    • Clinique St. Etienne
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Bourg-En-Bresse, France, 01012
    • Centre Hospitalier de Fleyriat
  • Bourgoin-Jallieu, France, 38300
    • Centre Hospitalier de Bourgoin - Jallieu
  • Brive, France, 19101
    • Centre Hospitalier General
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Dijon, France, 21034
    • Hopital Du Bocage
  • Dijon, France, 21033
    • Faculte de Medecine
  • Forbach, France, 57600
    • Centre Hospitalier Maie Madeleine
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13273
    • Institut J. Paoli and I. Calmettes
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes-Saint Herblain, France, 44805
    • CRLCC Nantes - Atlantique
  • Orleans, France, 45067
    • CHR D'Orleans - Hopital de la Source
  • Reims, France, 51056
    • Institut Jean Godinot
  • Reims, France, 51056
    • St Joseph's Medical Center
  • Reims, France, 51092
    • Centre Hospitalier Universitaire
  • Rennes, France, 35064
    • Centre Eugène Marquis
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint Cloud, France, 92210
    • Centre René Huguenin
  • Strasbourg, France, 67091
    • Hopitaux Universitaire de Strasbourg
  • Tarbes, France, 65013
    • Centre hospitalier de Tarbes
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Valence, France, 26000
    • Centre Hospitalier Valence
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Vannes, France, 56260
    • Centre Hospitalier P. Chubert
  • Vichy, France, 03201
    • Centre Hospitalier Regionale de Vichy
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven stage III adenocarcinoma of the colon that has been curatively resected within past 42 days
• No metastatic disease

• Node positive

  • No more than 4 nodes affected (Tx, N2, M0) AND/OR
  • N1 or N2 with perforation and/or occlusion
• No prior rectal cancer within 10 cm of anal margin or that was treated with preoperative radiotherapy
• No prior inflammatory disease of the intestine

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin less than 1.25 times upper limit of normal (ULN)
• SGOT and SGPT less than 3 times ULN
• Alkaline phosphatase less than 3 times ULN

Renal:

• Not specified

Cardiovascular:

• No myocardial infarction within past 6 months
• No insufficient cardiac function

Other:

• No other serious medical illness
• No active infection
• No other malignancy except skin cancer or carcinoma in situ of the cervix
• No psychological or social condition that would preclude study
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics
• No prior extensive intestinal resection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Federation Francophone de Cancerologie Digestive
• Investigators: Study Chair: Marc Ychou, MD, PhD, Institut du Cancer de Montpellier - Val d'Aurelle; Study Chair: Jean Faivre, Federation Francophone de Cancerologie Digestive

Publications and helpful links

General Publications

• Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, Viret F, Becouarn Y, Bouche O, Gamelin E, Ducreux M, Conroy T, Seitz JF, Bedenne L, Kramar A. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol. 2009 Apr;20(4):674-80. doi: 10.1093/annonc/mdn680. Epub 2009 Jan 29.
• Cote JF, Kirzin S, Kramar A, Mosnier JF, Diebold MD, Soubeyran I, Thirouard AS, Selves J, Laurent-Puig P, Ychou M. UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin Cancer Res. 2007 Jun 1;13(11):3269-75. doi: 10.1158/1078-0432.CCR-06-2290. Epub 2007 May 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 1998
• Primary Completion (Actual): September 26, 2005
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: adenocarcinoma of the colon; stage III colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000067967; FRE-FNCLCC-ACCORD-2; FFCD-9802; EU-20014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No