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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the colon stage III colon cancer	Drug: celecoxib  Drug: fluorouracil  Drug: leucovorin calcium  Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase III

Further Study Details: 

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.

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

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

Austria
      Allgemeines Krankenhaus der Stadt Wien, Vienna,  A-1090,  Austria; Recruiting
      Allgemeines Krankenhaus, Wiener Neustadt,  2700,  Austria; Recruiting
      Innsbruck Universitaetsklinik, Innsbruck,  A-6020,  Austria; Recruiting
      Karl-Franzens-University Graz, Graz,  A-8010,  Austria; Recruiting
      Krankenhaus der Elisabethinen, Linz,  4020,  Austria; Recruiting
      Landeskrankenanstalten - Salzburg, Salzburg,  A-5020,  Austria; Recruiting
      St. Vincent's Hospital, Linz Donau,  4010,  Austria; Recruiting
Belgium
      CHU Liege - Domaine Universitaire du Sart Tilman, LIEGE,  B-4000,  Belgium; Recruiting
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium; Recruiting
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium; Recruiting
      St. Elizabeth Ziekenhuis, TURNHOUT,  2300,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
      Ziekenhuis Network Antwerpen Middelheim, Antwerpen,  B-2020,  Belgium; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Catharina Ziekenhuis, Eindhoven,  5602 ZA,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Deventer Ziekenhuisen, Deventer,  7415 CM,  Netherlands; Recruiting
      Erasmus MC - Sophia Children's Hospital, Rotterdam,  3015 GJ,  Netherlands; Recruiting
      Gelre Ziekenhuizen - Lokatie Lukas, Apeldoorn,  7334 DZ,  Netherlands; Recruiting
      Ikazia Ziekenhuis, Rotterdam,  NL-3083,  Netherlands; Recruiting
      Isala Klinieken - locatie Weezenlanden, Zwolle,  NL-8000 GM,  Netherlands; Recruiting
      Jeroen Bosch Ziekenhuis, 's-Hertogenbosch,  5211 NL,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2333 ZA,  Netherlands; Recruiting
      Medisch Centrum Haaglanden, S. Gravenhage,  2501 CK,  Netherlands; Recruiting
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands; Recruiting
      Nijmegen University Cancer Centre, Nijmegen,  6500 HB,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
      Rijnstate Hospital, ARNHEM,  6800 TA,  Netherlands; Recruiting
      Schieland Ziekenhuis, Schiedam,  NL-3116,  Netherlands; Recruiting
      Sint Antonius Ziekenhuis, Nieuwegein,  3435 CM,  Netherlands; Recruiting
      Streekziekenhuis Koningin Beatrix, Winterswyk,  7101 BN,  Netherlands; Recruiting
      University Medical Center Groningen, Groningen,  9700 RB,  Netherlands; Recruiting
      Waterlandziekenhuis, Purmerend,  1440 AG,  Netherlands; Recruiting
      Ziekenhuis de Honte, Terneuzen,  NL-4535,  Netherlands; Recruiting
      Ziekenhuis Lievensberg, Bergen-op-Zoom,  4624 VT,  Netherlands; Recruiting
      Ziekenhuis St Jansdal, Harderwijk,  3840 AC,  Netherlands; Recruiting

Study chairs or principal investigators

Cornelis J.H. van de Velde, MD, PhD, FRCS, FRCPS,  Leiden University Medical Center   
Dirk J. Richel, MD, PhD,  Academisch Medisch Centrum   
Michel Ducreux, MD, PhD,  Institut Gustave Roussy   

Study ID Numbers:  CDR0000367335; EORTC-40023; PETACC-5; NCT00085163
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085163
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08