Clinical trial NCT00005979: Combination Chemotherapy With or Without Irinotecan in Treating Patients With Stage III Colon Cancer
Official title: Phase III Randomized Study of Intensive Adjuvant Chemotherapy for Resected Colon Cancer at High Risk of Recurrence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage III colon cancer
adenocarcinoma of the colon
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Federation Francophone de Cancerologie Digestive
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Bayonne
country: France
facility: Clinique St. Etienne
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bourg-En-Bresse
country: France
facility: Centre Hospitalier de Fleyriat
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier de Bourgoin - Jallieu
city: Brive
country: France
facility: Centre Hospitalier General
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dijon
country: France
facility: Faculte de Medecine
city: Dijon
country: France
facility: Hopital Du Bocage
city: Forbach
country: France
facility: Centre Hospitalier Maie Madeleine
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: St Joseph's Medical Center
city: Reims
country: France
facility: Centre Hospitalier Universitaire
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg
city: Tarbes
country: France
facility: Centre Hospitalier de Tarbes
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Valence
country: France
facility: Centre Hospitalier Valence
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Vannes
country: France
facility: Centre Hospitalier P. Chubert
city: Vichy
country: France
facility: Centre Hospitalier Regionale de Vichy
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Marc Ychou, MD, PhD
role: STUDY_CHAIR
affiliation: Federation Francophone de Cancerologie Digestive
name: Jean Faivre
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.