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Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00064181
Recruitment Status : Completed
First Posted : July 9, 2003
Last Update Posted : September 24, 2012
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy such as irinotecan, capecitabine, leucovorin, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor. It is not yet known which combination chemotherapy regimen with or without celecoxib is more effective in treating metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens and celecoxib to see how well they work compared to two combination chemotherapy regimens alone in treating patients with metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: FOLFIRI regimen Drug: capecitabine Drug: celecoxib Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Phase 3

Detailed Description:


  • Compare the progression-free survival of patients with metastatic colorectal cancer treated with capecitabine and irinotecan vs fluorouracil, leucovorin calcium, and irinotecan with vs without celecoxib.
  • Compare the safety of these regimens in these patients.
  • Compare the response rate in patients treated with these regimens.
  • Compare the time to treatment failure and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind*, multicenter study. Patients are stratified according to participating center, prior adjuvant therapy (yes vs no), and risk group (poor vs intermediate vs good). Patients are randomized to 1 of 4 treatment arms.

  • Arm I: Patients receive irinotecan IV over 30-90 minutes on days 1 and 22; oral capecitabine twice daily on days 1-15 and 22-36; and oral celecoxib twice daily on days 1-42.
  • Arm II: Patients receive irinotecan and capecitabine as in arm I and oral placebo twice daily on days 1-42.
  • Arm III: Patients receive irinotecan IV over 30-90 minutes on days 1, 15, and 29; leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1, 2, 15, 16, 29, and 30; and oral celecoxib twice daily on days 1-42.
  • Arm IV: Patients receive irinotecan, CF, and 5-FU as in arm III and oral placebo twice daily on days 1-42.

In all arms, treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. If all chemotherapy is discontinued due to toxicity, patients may continue celecoxib or placebo until disease progression, unacceptable toxicity, or starting a new cytotoxic regimen.

NOTE: *The double-blind treatment only applies to the celecoxib and placebo randomization

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 692 patients (173 per treatment arm) will be accrued for this study within 3.5 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Masking: Double
Primary Purpose: Treatment
Official Title: Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer
Study Start Date : May 2003
Actual Primary Completion Date : January 2005

Resource links provided by the National Library of Medicine

Drug Information available for: Celecoxib

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the colon or rectum
  • Metastatic disease
  • Measurable disease

    • Patients who received prior radiotherapy must have measurable or evaluable disease outside the radiotherapy field
  • No CNS metastases



  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified


  • WBC at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • AST and ALT no greater than 2.5 times ULN (5 times ULN in the presence of liver metastases)


  • Creatinine clearance at least 51 mL/min
  • No severe renal impairment


  • No severe cardiac disease
  • No uncontrolled angina pectoris
  • No myocardial infarction within the past 6 months


  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • No active Crohn's disease
  • No other malignancy except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No other uncontrolled severe medical condition
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up


Biologic therapy

  • No concurrent active or passive immunotherapy for colon cancer


  • No prior chemotherapy for metastatic disease

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy


  • Not specified


  • At least 6 months since prior adjuvant therapy
  • More than 4 weeks since prior investigational drugs
  • No concurrent sorivudine or chemically related analogues (e.g., brivudine)
  • No other concurrent investigational drugs
  • No other concurrent cytotoxic agents
  • No concurrent prophylactic fluconazole
  • No concurrent or planned cyclo-oxygenase-2 (COX-2) inhibitors or nonsteroidal anti-inflammatory drugs
  • No concurrent chronic use of full-dose aspirin (325 mg/day or greater)

    • Concurrent low-dose (cardioprotective) aspirin prophylaxis (no more than 325 mg every other day OR no more than 162.5 mg per day) allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00064181

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Ziekenhuis Network Antwerpen Middelheim
Antwerp, Belgium, 2020
Institut Jules Bordet
Brussels, Belgium, 1000
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Cazk Groeninghe - Campus St-Niklaas
Kortrijk, Belgium, B-8500
St. Elizabeth Ziekenhuis
Turnhout, Belgium, 2300
National Cancer Institute - Cairo
Cairo, Egypt
Charite - Campus Charite Mitte
Berlin, Germany, D-10117
General Hospital
Celle, Germany, 29223
Universitatsklinikum Carl Gustav Carl Carus
Dresden, Germany, D-01307
Kliniken Essen - Mitte
Essen, Germany, D-45136
Klinikum der J.W. Goethe Universitaet
Frankfurt, Germany, D-60590
Klinikum der Albert - Ludwigs - Universitaet Freiburg
Freiburg, Germany, D-79106
Allgemeines Krankenhaus Hagen
Hagen, Germany, D-58095
Allgemeines Krankenhaus Altona
Hamburg, Germany, 22763
Universitaets-Krankenhaus Eppendorf
Hamburg, Germany, D-20246
St. Marien Hospital
Hamm, Germany, 59065
Westpfalz-Klinikum GmbH
Kaiserslautern, Germany, D-67653
Landau, Germany, D-76829
Onkologische Schwerpunktpraxis Leer
Leer, Germany, D-26789
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
Kreiskrankenhaus Meissen
Meissen, Germany, D-01662
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Eberhard Karls Universitaet
Tuebingen, Germany, D-72076
Universitaets-Hautklinik Wuerzburg
Wuerzburg, Germany, D-97080
National Institute of Oncology
Budapest, Hungary, 1122
Rambam Medical Center
Haifa, Israel, 31096
Wolfson Medical Center
Holon, Israel, 58100
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: Claus-Henning Koehne, MD Klinikum Oldenburg

Publications of Results:
De Grève J, Koehne C, Hartmann J, et al.: Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015. [Abstract] J Clin Oncol 24 (Suppl 18): A-3577, 2006.
Kohne C, De Greve J, Bokemeyer C, et al.: Capecitabine plus irinotecan versus 5-FU/FA/irinotecan +/- celecoxib in first line treatment of metastatic colorectal cancer. Safety results of the prospective multicenter EORTC phase III study 40015. [Abstract] J Clin Oncol 23 (Suppl 16): A-3525, 252s, 2005.

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00064181     History of Changes
Other Study ID Numbers: EORTC-40015
First Posted: July 9, 2003    Key Record Dates
Last Update Posted: September 24, 2012
Last Verified: September 2012
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer
stage IV rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents