Celecoxib Combined With Fluorouracil and Leucovorin in Treating Patients With Resected Stage III Adenocarcinoma (Cancer) of the Colon

NCT ID: NCT00085163

Last Updated: 2015-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. It is not yet known whether fluorouracil and leucovorin are more effective with or without celecoxib in treating resected stage III adenocarcinoma (cancer) of the colon.

PURPOSE: This randomized phase III trial is studying celecoxib, fluorouracil, and leucovorin to see how well they work compared to fluorouracil and leucovorin in treating patients who have undergone surgery for stage III colon cancer.

Detailed Description

OBJECTIVES:

Primary

• Compare disease-free survival of patients with curatively resected stage III adenocarcinoma of the colon treated with adjuvant fluorouracil and leucovorin calcium with or without celecoxib.

Secondary

• Compare the overall survival, the occurrence of new primary colon cancer, and the development of new polyps in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to ≥ 4 tumor-positive lymph nodes (yes vs no), form of adjuvant chemotherapy (infusional vs bolus), low-dose aspirin for cardiovascular prophylaxis (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil and leucovorin calcium IV for up to 6 courses in the absence of disease recurrence or unacceptable toxicity. Patients also receive oral celecoxib twice daily.
• Arm II: Patients receive oral placebo twice daily and fluorouracil and leucovorin calcium as in arm I.

In both arms, treatment with celecoxib or placebo continues for 3 years in the absence of disease recurrence or unacceptable toxicity.

Patients are followed annually for 2 years.

PROJECTED ACCRUAL: A total of 1,450 patients (725 per treatment arm) will be accrued for this study within 2 years.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

celecoxib

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon

• 15 cm above anal verge
• Stage III disease (any pT, N1-2, M0)
• No rectal cancer
• Must have undergone curative radical resection (R0 resection) within the past 6 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST ≤ 5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• None of the following conditions within the past 6 months:

• Myocardial infarction
• Unstable angina
• Symptomatic congestive heart failure
• Serious uncontrolled cardiac arrhythmia
• Cerebrovascular accident or transient ischemic attack
• Deep vein thrombosis
• Other significant thromboembolic event

Pulmonary

• No pulmonary embolism within the past 6 months

Gastrointestinal

• No active gastric or duodenal ulceration within the past year
• No gastrointestinal bleeding within the past year
• No partial or complete bowel obstruction
• No known chronic malabsorption
• No active inflammatory bowel disease or chronic diarrhea (more than 4 stools/day)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No AIDS-related illness
• No prior hypersensitivity to fluorouracil, leucovorin calcium, celecoxib, other COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides
• No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation, study drug administration, or study results interpretation
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No concurrent active infection
• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent sargramostim (GM-CSF) or molgramostim

Chemotherapy

• Not specified

Endocrine therapy

• No more than 4 weeks of concurrent orally/nasally inhaled steroids over a 6-month period

• Concurrent mometasone (or fluticasone) allowed if patients require ≥ 4 weeks of inhaled steroid therapy
• At least 30 days since other prior steroids
• No concurrent hormonal therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• No prior total colectomy or other major surgery that would result in substantial alteration in transit to absorption of oral medication

Other

• More than 30 days since prior investigational medication
• No prior systemic anticancer treatment for colon cancer
• No concurrent prophylactic fluconazole
• No concurrent lithium
• No concurrent chronic* use of full dose aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase-2 (COX-2) inhibitors

• Aspirin at cardioprotective doses (i.e., 80 mg daily or equivalent) allowed
• No concurrent participation in any other clinical study
• No other concurrent experimental agents (e.g., other COX-2 inhibitors, matrix metalloproteinase inhibitors, inhibitors of the vascular endothelial growth factor/Flk-1 pathway, or inhibitors of the epidermal growth factor receptor pathway) NOTE: *Chronic use is defined as a frequency of 7 consecutive days (1 week) for more than 3 weeks/year or more than 21 days throughout the year

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dutch Colorectal Cancer Group (DCCG)

UNKNOWN

Sponsor Role: collaborator

Arbeitsgemeinschaft fur Internistische Onkologie

OTHER

Sponsor Role: collaborator

Onkologie

UNKNOWN

Sponsor Role: collaborator

Egyptian Foundation For Cancer Research

OTHER

Sponsor Role: collaborator

EORTC GI Group (EORTC 40023)

UNKNOWN

Sponsor Role: collaborator

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: collaborator

GCCD-APIO - Grupo Cooperativo do Cancro Digestivo da Associação Portuguesa de Investigação

UNKNOWN

Sponsor Role: collaborator

Oncológica

UNKNOWN

Sponsor Role: collaborator

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

OTHER

Sponsor Role: collaborator

GOCCI - Gruppo Oncologico Chirurgico Cooperativo Italiano

UNKNOWN

Sponsor Role: collaborator

GOIRC - Gruppo Oncologico Italiano di Ricerca Clinica

UNKNOWN

Sponsor Role: collaborator

SG - Scandinavian Group

UNKNOWN

Sponsor Role: collaborator

TTD - Grupo Español para el Tratamiento de Tumores Digestivos

UNKNOWN

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelis J.H. van de Velde, MD, PhD, FRCS, FRCPS

Role: STUDY_CHAIR

Leiden University Medical Center

Dirk J. Richel, MD, PhD

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Michel Ducreux, MD, PhD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Karl-Franzens-University Graz

Graz, , Austria

Innsbruck Universitaetsklinik

Innsbruck, , Austria

Krankenhaus der Elisabethinen

Linz, , Austria

St. Vincent's Hospital

Linz Donau, , Austria

Landeskrankenanstalten - Salzburg

Salzburg, , Austria

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Allgemeines Krankenhaus

Wiener Neustadt, , Austria

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, , Belgium

St. Elizabeth Ziekenhuis

Turnhout, , Belgium

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, , Netherlands

Gelre Ziekenhuizen - Lokatie Lukas

Apeldoorn, , Netherlands

Rijnstate Hospital

Arnhem, , Netherlands

Ziekenhuis Lievensberg

Bergen op Zoom, , Netherlands

Deventer Ziekenhuisen

Deventer, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Ziekenhuis St Jansdal

Harderwijk, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Sint Antonius Ziekenhuis

Nieuwegein, , Netherlands

Nijmegen Cancer Center at Radboud University Medical Center

Nijmegen, , Netherlands

Waterlandziekenhuis

Purmerend, , Netherlands

Daniel Den Hoed Cancer Center at Erasmus Medical Center

Rotterdam, , Netherlands

Erasmus MC - Sophia Children's Hospital

Rotterdam, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Schieland Ziekenhuis

Schiedam, , Netherlands

Ziekenhuis de Honte

Terneuzen, , Netherlands

Medisch Centrum Haaglanden

The Hague, , Netherlands

Streekziekenhuis Koningin Beatrix

Winterswyk, , Netherlands

Isala Klinieken - locatie Weezenlanden

Zwolle, , Netherlands

Countries

Austria; Belgium; Netherlands

Other Identifiers

EORTC-40023

Identifier Type: -

Identifier Source: secondary_id

PETACC-5

Identifier Type: -

Identifier Source: secondary_id

EORTC-40023

Identifier Type: -

Identifier Source: org_study_id