Clinical trial NCT00004150: High-Dose Fluorouracil With or Without Leucovorin Compared With Standard Fluorouracil Plus Leucovorin Following Surgery in Treating Patients With 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage III colon cancer
adenocarcinoma of the colon
mucinous adenocarcinoma of the colon
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: Federation Francophone de Cancerologie Digestive
name: Grupo Espanol Tratamiento Tumores Digestivos
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
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. 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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Ziekenhuis Network Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Angers
country: France
facility: Centre Hospitalier Regional et Universitaire d'Angers
city: Bayonne
country: France
facility: Clinique St. Etienne
city: Belfort
country: France
facility: Centre Hospitalier General
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Bois-Guillaume
country: France
facility: Clinique du Cedre
city: Boulogne Billancourt
country: France
facility: CHU Ambroise Pare
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier de Bourgoin - Jallieu
city: Brive
country: France
facility: Centre Hospitalier General
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chalons-en-Champagne
country: France
facility: Centre Hospitalier de Chalons - en - Champagne
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Evreux
country: France
facility: Clinique Pasteur
city: Les Sables d'Olonne
country: France
facility: Cabinet de Gastro-Enterologie
city: Lille
country: France
facility: Centre Hospital Universitaire Hop Huriez
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Montauban
country: France
facility: Clinique du Pont de Chaume
city: Montpellier
country: France
facility: Hopital St. Eloi
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Hopital de l'Archet
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Cochin
city: Pontoise
country: France
facility: Clinique Ste - Marie
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: Polyclinique De Courlancy
city: Saint Nazaire
country: France
facility: Centre Hospitalier General de Saint Nazaire
city: St. Esprit
country: France
facility: Centre Hospitalier D'Agen
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: CHU Rangueil
city: Valence
country: France
facility: Nouvelle Clinique Generale
city: Vandoeuvre-les-Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Verdun
country: France
facility: Centre Hospitalier General - St. Nicolas
city: Vichy
country: France
facility: Centre Hospitalier Regionale de Vichy
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Roermond
country: Netherlands
facility: Saint Laurentius Ziekenhuis
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Albacete
country: Spain
facility: Hospital General
city: Alcoi Alicante
country: Spain
facility: Hospital Virgen de los Lirios
city: Alicante
country: Spain
facility: Hospital General - Alicante
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barbastro
country: Spain
facility: Hospital de Barbastro
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Institut d'Oncologia Corachan
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz I Sant Pau
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Consorci Hospitalari de la Creu Roia
city: Barcelona
country: Spain
facility: Hospital de L'esperit Sant
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta Del Mar
city: Cordoba
country: Spain
facility: Hospital Universarito "Reina Sofia"
city: Cuenca
country: Spain
facility: Hospital Virgen de Luz
city: Elche Alicante
country: Spain
facility: Hospital Universitario de Elche
city: Granada
country: Spain
facility: Hospital General Virgen de las Nieves
city: Guadalajara
country: Spain
facility: Hospital General Universitario De Guadalajara
city: Jaen
country: Spain
facility: Residencia Sanitaria de Jaen
city: Jerez
country: Spain
facility: Hospital General de Jerez
city: La Laguna
country: Spain
facility: Hospital Universitario Canarias
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz - Clin. N.S.
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Malaga
country: Spain
facility: Hospital Regional Carlos Haya De Malaga
city: Merida
country: Spain
facility: Hospital De Merida
city: Pamplona
country: Spain
facility: Hospital De Navarra
city: Sabadell
country: Spain
facility: Consorci Hospitalari del Parc Tauli
city: Sagunto
country: Spain
facility: Hospital de Sagunto
city: Salamanca
country: Spain
facility: Hospital Virgen de la Vega
city: San Juan
country: Spain
facility: Hospital Universitari Sant Joan d'Alacant
city: Sant Pere de Ribes
country: Spain
facility: Hospital - Residencia Sant Camil
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Ntra. Sra. de la Candelaria
city: Terrassa
country: Spain
facility: Hospital Consorci Sanitari De Terrassa
city: Valencia
country: Spain
facility: Instituto Valenciano De Oncologia
city: Valencia
country: Spain
facility: Hospital General Universitario Valencia
city: Vitoria
country: Spain
facility: Hospital Txagorritxu
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
Study officials:
affiliation: Klinikum Oldenburg
name: Claus-Henning Koehne, MD
affiliation: Saint Laurentius Ziekenhuis
name: G. Leam
affiliation: Hopital Du Bocage
name: Laurent Bedenne, MD
affiliation: Hospital Universitario de Elche
name: Alfredo Carrato-Mena, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.