Clinical trial NCT00004885: Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients With Metastatic Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-04-12
Enrollment: 430
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 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Cairo
country: Egypt
facility: National Cancer Institute of Egypt
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Aachen
country: Germany
facility: PZB - Praxenzentrum
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Braunschweig
country: Germany
facility: Haematology-Oncology
city: Dresden
country: Germany
facility: Humaine Klinik Dresden GmbH
city: Dresden
country: Germany
facility: Medizinische Klinik I
city: Duesseldorf
country: Germany
facility: Universitaetsklinik Duesseldorf
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Emden
country: Germany
facility: Hans-Susemihl-Krankenhaus
city: Essen
country: Germany
facility: Haemato-Onkol. Praxis
city: Essen
country: Germany
facility: Universitaetsklinik und Strahlenklinik - Essen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder)
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hagen
country: Germany
facility: Marien Hospital
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Halle Saale
country: Germany
facility: Martin Luther Universitaet
city: Halle
country: Germany
facility: Internistisch - Onkologische Gemeinschaftspraxis
city: Hamburg
country: Germany
facility: Hermann-Holthusen Institute for Radiotherapy
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hannover
country: Germany
facility: Henriettenstiftung - Chirurgische Klinik
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Herne
country: Germany
facility: Marienhospital/Ruhr University Bochum
city: Homburg/Saar
country: Germany
facility: Universitatsklinik, Saarland
city: Koblenz
country: Germany
facility: Haematologisch-Oncologische Praxis
city: Lemgo
country: Germany
facility: Klinikum Lippe-Lemgo
city: Ludwigslust
country: Germany
facility: Stift Bethlehem
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg
city: Magdeburg
country: Germany
facility: Otto-Von-Guericke-Universitaet Magdeburg
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Munich
country: Germany
facility: Muenchen Onkol. Praxis Elisenhof
city: Neustadt
country: Germany
facility: Praxis Innere Medizin
city: Neustadt
country: Germany
facility: Kreiskrankenhaus Neustadt A. Rbge. des Landkreises Hannover
city: Nuremberg (Nurnberg)
country: Germany
facility: Klinikum Nurnberg
city: Postdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Quedlinburg
country: Germany
facility: Klinikum D. Ch. Erxleben
city: Riesa
country: Germany
facility: Kreiskrankenhaus Riesa
city: Rostock
country: Germany
facility: University of Rostock
city: Schwarzenberg
country: Germany
facility: Fachkrankenhaus Marienstift
city: Stuttgart
country: Germany
facility: Katharinenhospital
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet
city: Ulm
country: Germany
facility: Klinikum der Universitaet Ulm
city: Wernigerode
country: Germany
facility: Harz-Klinikum Wernigerode GMBH - Medizinische Klinik
city: Wolfsburg
country: Germany
facility: Klinikum der Stadt Wolfsburg
city: Worms
country: Germany
facility: Gemeinschaftspraxis
city: Wuerzburg
country: Germany
facility: Medizinische Poliklinik, Universitaet Wuerzburg
city: Wuppertal
country: Germany
facility: Witten University - Klinikum Wuppertal
city: Alba
country: Italy
facility: Ospedale San Lazzaro
city: Roermond
country: Netherlands
facility: Saint Laurentius Ziekenhuis
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Cancer Research Center
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
Study officials:
affiliation: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
name: Claus-Henning Koehne, MD
role: STUDY_CHAIR
References:
citation: Kohne CH, van Cutsem E, Wils J, Bokemeyer C, El-Serafi M, Lutz MP, Lorenz M, Reichardt P, Ruckle-Lanz H, Frickhofen N, Fuchs R, Mergenthaler HG, Langenbuch T, Vanhoefer U, Rougier P, Voigtmann R, Muller L, Genicot B, Anak O, Nordlinger B; European Organisation for Research and Treatment of Cancer Gastrointestinal Group. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol. 2005 Aug 1;23(22):4856-65. doi: 10.1200/JCO.2005.05.546. Epub 2005 Jun 6.
citation: 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.
citation: 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.