High-Dose Fluorouracil With or Without Leucovorin Compared With Standard Fluorouracil Plus Leucovorin Following Surgery in Treating Patients With Stage III Colon Cancer

Pan-European Trials in Adjuvant Colon Cancer (PETACC-2): Randomized Phase III Intergroup Trial of High-Dose Infusional 5-FU (+ or - Folinic Acid) Versus Standard Bolus 5-FU/Folinic Acid

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: This randomized phase III trial is studying high-dose fluorouracil with or without leucovorin to see how well it works compared to standard-dose fluorouracil and leucovorin in treating patients who have undergone surgery for stage III colon cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Procedure: adjuvant therapy

Detailed Description

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.
• Arm II: 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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED

Collaborators and Investigators

• Sponsor: Robert Roessle Klinik
• Collaborators: Federation Francophone de Cancerologie Digestive; European Organisation for Research and Treatment of Cancer - EORTC; Grupo Espanol Tratamiento Tumores Digestivos
• Investigators: Claus-Henning Koehne, MD, Klinikum Oldenburg; G. Leam, Saint Laurentius Ziekenhuis; Laurent Bedenne, MD, Hôpital du Bocage; Study Chair: Alfredo Carrato-Mena, MD, Hospital Universitario de Elche

Publications and helpful links

General Publications

• Fensterer H, Radlwimmer B, Strater J, Buchholz M, Aust DE, Julie C, Radvanyi F, Nordlinger B, Belluco C, Van Cutsem E, Kohne CH, Kestler HA, Schwaenen C, Nessling M, Lutz MP, Lichter P, Gress TM; EORTC Gastrointestinal (GI) Group. Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks. BMC Cancer. 2007 Apr 2;7:58. doi: 10.1186/1471-2407-7-58.
• Carrato A, Köhne C, Bedenne L, et al.: Folinic acid modulated bolus 5-FU or infusional 5-FU for adjuvant treatment of patients of UICC stage III colon cancer: preliminary analysis of the PETACC-2-study. [Abstract] J Clin Oncol 24 (Suppl 18): A-3563, 2006.

Study record dates

Study Major Dates

• Study Start: March 1, 1999
• Study Completion (ACTUAL): April 1, 2007

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): November 6, 2013
• Last Update Submitted That Met QC Criteria: November 5, 2013
• Last Verified: February 1, 2001

More Information

Terms related to this study

• Keywords: adenocarcinoma of the colon; stage III colon cancer; mucinous adenocarcinoma of the colon
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000067383; PETACC-2; EORTC-40963; FFCD-PETACC-2; GETTD-PETACC-2