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

Condition(s) targeted: Colorectal Cancer

Intervention: fluorouracil (Drug); leucovorin calcium (Drug); adjuvant therapy (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Robert Roessle Comprehensive Cancer Center - Charite Campus Buch

Official(s) and/or principal investigator(s):
Claus-Henning Koehne, MD, Affiliation: Klinikum Oldenburg
G. Leam, Affiliation: Saint Laurentius Ziekenhuis
Laurent Bedenne, MD, Affiliation: Hopital Du Bocage
Alfredo Carrato-Mena, MD, Study Chair, Affiliation: Hospital Universitario de Elche

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.

Official title: 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

Study design: Treatment, Randomized, Active Control

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): 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

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

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

Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin D-13122, Germany

Saint Laurentius Ziekenhuis, Roermond 6043 CV, Netherlands

Institute of Oncology and Radiology of Serbia, Belgrade 11000, Serbia and Montenegro

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

Clinical trial summary from the National Cancer Institute's PDQ® database

Related 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.

Starting date: March 1999
Last updated: May 23, 2008