RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective for colon cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of high-dose fluorouracil with or without leucovorin compared with standard-dose fluorouracil plus leucovorin following surgery in treating patients who have stage III colon cancer.

Condition	Treatment or Intervention	Phase
stage III colon cancer adenocarcinoma of the colon mucinous adenocarcinoma of the colon	Drug: fluorouracil  Drug: leucovorin calcium  Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: high-dose chemotherapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare recurrence-free survival and duration of survival in patients with stage III adenocarcinoma of the colon treated with adjuvant high-dose fluorouracil with or without leucovorin calcium versus standard fluorouracil with leucovorin calcium following curative radical resection.
• Compare the safety of these regimens in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to regional lymph node involvement (N1 (1-3 pericolic lymph nodes) vs N2 (more than 3 pericolic lymph nodes) and participating center.

Patients are randomized to one of two treatment arms.

• Arm I: Patients receive leucovorin calcium IV followed by fluorouracil IV on days 1-5. Treatment repeats every 4 weeks for 6 courses.
• Patients receive high-dose fluorouracil IV continuously over 48 hours weekly for 8 weeks. Treatment repeats every 8 weeks for 3 courses. OR
• Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 24 hours weekly for 6 weeks. Treatment repeats every 7 weeks for 3 courses. OR
• Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV bolus and then fluorouracil IV continuously over 22 hours on days 1 and 2. Treatment repeats every 2 weeks for 12 courses. Patients are followed at 1 month, every 6 months for 4.5 years, and then annually thereafter until death.

PROJECTED ACCRUAL: Approximately 1,600 patients (800 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III adenocarcinoma or mucinous adenocarcinoma of the colon
• Must have had curative radical resection within 56 days prior to study
• No local tumor therapy (i.e., polypectomy, local excision or limited intestinal resection)

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 10.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No severe coronary heart disease
• No New York Heart Association class III or IV heart failure

Other:

• No other malignancy within the past 10 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No uncontrolled infection
• No other severe disease
• No known allergy to leucovorin calcium
• No known familial adenomatous polyposis, Crohn's disease, or ulcerative colitis
• No hereditary syndrome (e.g., Gardner's syndrome, Turcot's syndrome, hereditary nonpolyposis colon cancer)
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for colon cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for colon cancer

Surgery:

• See Disease Characteristics

Other:

• No other concurrent systemic anticancer therapy

Belgium
      Centre Hospitalier Peltzer-La Tourelle, VERVIERS,  B-4800,  Belgium
      CHU Liege - Domaine Universitaire du Sart Tilman, LIEGE,  B-4000,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
      Ziekenhuis Network Antwerpen Middelheim, Antwerpen,  B-2020,  Belgium
France
      Cabinet de Gastro-Enterologie, Les Sables-d'Olonne,  85100,  France
      Centre de Lutte Contre le Cancer Georges-Francois Leclerc, Dijon,  21079,  France
      Centre Hospital Universitaire Hop Huriez, Lille,  59037,  France
      Centre Hospitalier D'Agen, St. Esprit,  47000,  France
      Centre Hospitalier de Bourgoin - Jallieu, Bourgoin-Jallieu,  38300,  France
      Centre Hospitalier de Chalons - en - Champagne, Chalons-en-Champagne,  51000,  France
      Centre Hospitalier de Meaux, Meaux,  77104,  France
      Centre Hospitalier General - St. Nicolas, Verdun,  55107,  France
      Centre Hospitalier General de Saint Nazaire, Saint-Nazaire,  44600,  France
      Centre Hospitalier General, Belfort,  90000,  France
      Centre Hospitalier General, Brive,  19101,  France
      Centre Hospitalier Regional et Universitaire d'Angers, Angers,  49033,  France
      Centre Hospitalier Regionale de Vichy, Vichy,  03201,  France
      Centre Hospitalier Universitaire de Dijon, Dijon,  21034,  France
      Centre Paul Strauss, Strasbourg,  67065,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR D'Orleans - Hopital de la Source, Orleans,  45100,  France
      CHU Ambroise Pare, Boulogne-Billancourt,  F-92104,  France
      CHU de Caen, Caen,  14033,  France
      CHU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France
      CHU Rangueil, Toulouse,  31403,  France
      Clinique du Cedre, Bois-Guillaume,  76230,  France
      Clinique du Pont de Chaume, Montauban,  82017,  France
      Clinique Pasteur, Evreux,  27000,  France
      Clinique St. Etienne, Bayonne,  64100,  France
      Clinique Ste - Marie, Pontoise,  95301,  France
      Hopital Bichat - Claude Bernard, Paris,  75018,  France
      Hopital Cochin, Paris,  75674,  France
      Hopital de la Croix Rousse, Lyon,  69317,  France
      Hopital de l'Archet, Nice,  F-06202,  France
      Hopital Louis Pasteur, Colmar,  68024,  France
      Hopital Saint Joseph, Marseille,  13008,  France
      Hopital St. Eloi, Montpellier,  34295,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
      Institut Jean Godinot, Reims,  51056,  France
      Nouvelle Clinique Generale, Valence,  26000,  France
      Polyclinique De Courlancy, Reims,  F-51100,  France
Germany
      Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin,  D-13122,  Germany
Netherlands
      Saint Laurentius Ziekenhuis, Roermond,  6043 CV,  Netherlands
Spain
      Consorci Hospitalari de la Creu Roia, Barcelona,  08906,  Spain
      Consorci Hospitalari del Parc Tauli, Sabadell,  08208,  Spain
      Fundacion Jimenez Diaz - Clin. N.S., Madrid,  28040,  Spain
      Hospital - Residencia Sant Camil, Sant Pere de Ribes,  08810,  Spain
      Hospital Clinico Universitario Lozano Blesa, Zaragoza,  50009,  Spain
      Hospital Consorci Sanitari De Terrassa, Terrassa,  08227,  Spain
      Hospital de Barbastro, Barbastro,  22300,  Spain
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain
      Hospital de L'esperit Sant, Barcelona,  08923,  Spain
      Hospital De Merida, Merida,  06800,  Spain
      Hospital De Navarra, Pamplona,  31008,  Spain
      Hospital de Sagunto, Sagunto,  46520,  Spain
      Hospital Del Mar, Barcelona,  08003,  Spain
      Hospital General - Alicante, Alicante,  3010,  Spain
      Hospital General de Jerez, Jerez,  11407,  Spain
      Hospital General Universitari Vall d'Hebron, Barcelona,  08035,  Spain
      Hospital General Universitario De Guadalajara, Guadalajara,  19002,  Spain
      Hospital General Universitario Valencia, Valencia,  46014,  Spain
      Hospital General Virgen de las Nieves, Granada,  18014,  Spain
      Hospital General, Albacete,  2006,  Spain
      Hospital Ntra. Sra. de la Candelaria, Santa Cruz de Tenerife,  38003,  Spain
      Hospital Regional Carlos Haya De Malaga, Malaga,  29010,  Spain
      Hospital Txagorritxu, Vitoria,  01009,  Spain
      Hospital Universarito "Reina Sofia", Cordoba,  14004,  Spain
      Hospital Universitari Germans Trias i Pujol, Badalona,  08916,  Spain
      Hospital Universitari Sant Joan d'Alacant, San Juan,  3550,  Spain
      Hospital Universitario Canarias, La Laguna,  38320,  Spain
      Hospital Universitario de Elche, Elche Alicante,  E-03203,  Spain
      Hospital Universitario Puerta Del Mar, Cadiz,  11000,  Spain
      Hospital Universitario San Carlos, Madrid,  28040,  Spain
      Hospital Virgen de la Vega, Salamanca,  37007,  Spain
      Hospital Virgen de los Lirios, Alcoi Alicante,  03800,  Spain
      Hospital Virgen de Luz, Cuenca,  16002,  Spain
      Institut d'Oncologia Corachan, Barcelona,  08017,  Spain
      Instituto Valenciano De Oncologia, Valencia,  46009,  Spain
      Residencia Sanitaria de Jaen, Jaen,  23007,  Spain
Yugoslavia
      Institute of Oncology and Radiology of Serbia, BELGRADE,  11000,  Yugoslavia

Study chairs or principal investigators

Claus-Henning Koehne, MD,  Klinikum Oldenburg   
G. Leam,  Saint Laurentius Ziekenhuis   
Laurent Bedenne, MD,  Hopital Du Bocage   
Alfredo Carrato-Mena, MD,  Study Chair,  Hospital Universitario de Elche   

Study ID Numbers:  CDR0000067383; PETACC-2; EORTC-40963; FFCD-PETACC-2; GETTD-PETACC-2; NCT00004150
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004150
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08