Fluorouracil and Leucovorin With or Without Irinotecan 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: NCT00004885
Recruitment Status : Completed
First Posted : April 12, 2004
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 use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether fluorouracil and leucovorin plus irinotecan is more effective than fluorouracil and leucovorin alone for colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have metastatic colorectal cancer.

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

Detailed Description:

OBJECTIVES: I. Compare the efficacy and toxicity of high-dose fluorouracil and leucovorin calcium with or without irinotecan in patients with metastatic adenocarcinoma of the colon or rectum. II. Compare progression-free survival, overall survival, response rate, and duration of response in patients treated with these 2 regimens. III. Compare quality of life of patients treated with these 2 regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV over 24 hours on days 1, 8, 15, 22, 29, and 36. Arm II: Patients receive irinotecan IV over 30 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV over 24 hours on days 1, 8, 15, 22, 29, and 36. Treatment in both arms repeats every 7 weeks in the absence of disease progression or unacceptable toxicity. Patients in arm I who develop disease progression begin second-line therapy comprising irinotecan, fluorouracil, and leucovorin calcium within 2 months of progression. Patients with complete response are taken off study after receiving treatment for one year. Quality of life is assessed before beginning study, after completion of each course, at 4 weeks after completion of study, and then every 2 months until disease progression or death. Patients are followed every 2 months until disease progression or death.

PROJECTED ACCRUAL: A total of 430 patients (215 per arm) will be accrued for this study within 2 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 430 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: CPT-11 in Combination With Weekly 24 Hour Infusion 5-FU Plus Folinic Acid Relative to Weekly 24 Hour Infusion 5-FU Plus Folinic Acid Alone in Patients With Advanced Colorectal Cancer
Study Start Date : July 1999
Actual Primary Completion Date : July 2001

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

DISEASE CHARACTERISTICS: Histologically proven metastatic adenocarcinoma of the colon or rectum Measurable or evaluable disease outside of any prior radiation port No CNS metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) (1.5 times ULN if liver metastasis present) AST and ALT no greater than 3 times ULN (5 times ULN if liver metastasis present) Renal: Creatinine no greater than 1.25 times ULN Cardiovascular: No severe cardiac disease No uncontrolled angina pectoris No myocardial infarction within the past 6 months Gastrointestinal: No unresolved bowel obstruction or subobstruction No uncontrolled Crohn's disease or ulcerative colitis No history of chronic diarrhea Other: No second malignancy except carcinoma in situ of the cervix or nonmelanomatous skin cancer No other uncontrolled severe medical condition Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for metastatic disease No prior adjuvant chemotherapy containing topoisomerase I inhibitors At least 6 months since other prior adjuvant chemotherapy Endocrine therapy: Concurrent corticosteroids allowed Radiotherapy: See Disease Characteristics Surgery: Not specified Other: At least 4 weeks since other prior investigational drugs No other concurrent anticancer therapy

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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): NCT00004885

  Hide Study Locations
Allgemeines Krankenhaus der Stadt Wien
Vienna, Austria, A-1090
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
National Cancer Institute of Egypt
Cairo, Egypt
Institut Gustave Roussy
Villejuif, France, F-94805
PZB - Praxenzentrum
Aachen, Germany, D-52062
Kreiskrankenhaus Aurich
Aurich, Germany, D-26603
Braunschweig, Germany, D-38100
Humaine Klinik Dresden GmbH
Dresden, Germany, 01326
Medizinische Klinik I
Dresden, Germany, D-01307
Universitaetsklinik Duesseldorf
Duesseldorf, Germany, D-40225
St. Johannes Hospital - Medical Klinik II
Duisburg, Germany, D-47166
Emden, Germany, D-26721
Haemato-Onkol. Praxis
Essen, Germany, 45127
Universitaetsklinik und Strahlenklinik - Essen
Essen, Germany, D-45122
Kliniken Essen-Mitte
Essen, Germany, D-45136
Klinikum Frankfurt (Oder)
Frankfurt (Oder), Germany, D-15236
Klinikum der J.W. Goethe Universitaet
Frankfurt, Germany, D-60590
Klinik Fuer Innere Medizin Hematology/Oncology, Ernst Moritz Armdt Universitaet
Greifswald, Germany, D-17487
Marien Hospital
Hagen, Germany, 58095
Allgemeines Krankenhaus Hagen
Hagen, Germany, D-58095
Martin Luther Universitaet
Halle Saale, Germany, DOH-0-6112
Internistisch - Onkologische Gemeinschaftspraxis
Halle, Germany, D-06110
Hermann-Holthusen Institute for Radiotherapy
Hamburg, Germany, D-20099
Haematologisch-Onkologische Praxis Altona
Hamburg, Germany, D-22765
Evangelische Krankenhaus Hamm
Hamm, Germany, DOH-5-9063
Henriettenstiftung - Chirurgische Klinik
Hannover, Germany, D-30171
Krankenhaus Siloah - Medizinische Klinik II
Hannover, Germany, D-30449
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Marienhospital/Ruhr University Bochum
Herne, Germany, DOH-4-4625
Universitatsklinik, Saarland
Homburg/Saar, Germany, D-66421
Haematologisch-Oncologische Praxis
Koblenz, Germany, D-56068
Klinikum Lippe-Lemgo
Lemgo, Germany, D-32657
Stift Bethlehem
Ludwigslust, Germany, D-19288
Staedtisches Klinikum Magdeburg
Magdeburg, Germany, D-39002
Otto-Von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
Johannes Gutenberg University
Mainz, Germany, D-55131
Muenchen Onkol. Praxis Elisenhof
Munich, Germany, D-80335
Praxis Innere Medizin
Neustadt, Germany, D-01844
Kreiskrankenhaus Neustadt A. Rbge. des Landkreises Hannover
Neustadt, Germany, D-31533
Klinikum Nurnberg
Nuremberg (Nurnberg), Germany, D-90419
Klinikum Ernst Von Bergmann
Postdam, Germany, D-14467
Klinikum D. Ch. Erxleben
Quedlinburg, Germany, D-06484
Kreiskrankenhaus Riesa
Riesa, Germany, D-01589
University of Rostock
Rostock, Germany, 18057
Fachkrankenhaus Marienstift
Schwarzenberg, Germany, D-08340
Stuttgart, Germany, D-70174
Eberhard Karls Universitaet
Tuebingen, Germany, D-72076
Klinikum der Universitaet Ulm
Ulm, Germany, D-89081
Harz-Klinikum Wernigerode GMBH - Medizinische Klinik
Wernigerode, Germany, D-38843
Klinikum der Stadt Wolfsburg
Wolfsburg, Germany, D-38440
Worms, Germany, DOH-6-7547
Medizinische Poliklinik, Universitaet Wuerzburg
Wuerzburg, Germany, D-97070
Witten University - Klinikum Wuppertal
Wuppertal, Germany, D-42283
Ospedale San Lazzaro
Alba, Italy, 12051
Saint Laurentius Ziekenhuis
Roermond, Netherlands, 6043 CV
Russian Federation
Russian Academy of Medical Sciences Cancer Research Center
Moscow, Russian Federation, 115478
South Africa
Medical Oncology Centre of Rosebank
Johannesburg, South Africa, 2193
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Claus-Henning Koehne, MD Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock

Publications of Results:
Kohne CH, Van Custem E, Wils JA, et al.: Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: results of EORTC GI Group study 40986. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1018, 2003.
Kohne C, van Cutsem E, Wils J, et al.: Weekly high dose infusional 5-FU plus folinic acid (FA) with or without irinotecan (IRI) in metastatic colorectal cancer (MCRC): interim safety results of EORTC study 40986. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-532, 2002.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00004885     History of Changes
Other Study ID Numbers: EORTC-40986
First Posted: April 12, 2004    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:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents