Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients With Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004885
• Other study ID #: EORTC-40986
• Secondary ID: EORTC-40986
• Status: Completed
• Phase: Phase 3
• First received: March 7, 2000
• Last updated: September 20, 2012
• Start date: July 1999

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 430
• Est. primary completion date: July 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• FOLFIRI regimen

• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus der Stadt Wien	Vienna
Belgium	U.Z. Gasthuisberg	Leuven
Egypt	National Cancer Institute of Egypt	Cairo
France	Institut Gustave Roussy	Villejuif
Germany	PZB - Praxenzentrum	Aachen
Germany	Kreiskrankenhaus Aurich	Aurich
Germany	Haematology-Oncology	Braunschweig
Germany	Humaine Klinik Dresden GmbH	Dresden
Germany	Medizinische Klinik I	Dresden
Germany	Universitaetsklinik Duesseldorf	Duesseldorf
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	Hans-Susemihl-Krankenhaus	Emden
Germany	Haemato-Onkol. Praxis	Essen
Germany	Kliniken Essen-Mitte	Essen
Germany	Universitaetsklinik und Strahlenklinik - Essen	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Klinikum Frankfurt (Oder)	Frankfurt (Oder)
Germany	Klinik Fuer Innere Medizin Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Allgemeines Krankenhaus Hagen	Hagen
Germany	Marien Hospital	Hagen
Germany	Internistisch - Onkologische Gemeinschaftspraxis	Halle
Germany	Martin Luther Universitaet	Halle Saale
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Hermann-Holthusen Institute for Radiotherapy	Hamburg
Germany	Evangelische Krankenhaus Hamm	Hamm
Germany	Henriettenstiftung - Chirurgische Klinik	Hannover
Germany	Krankenhaus Siloah - Medizinische Klinik II	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Marienhospital/Ruhr University Bochum	Herne
Germany	Universitatsklinik, Saarland	Homburg/Saar
Germany	Haematologisch-Oncologische Praxis	Koblenz
Germany	Klinikum Lippe-Lemgo	Lemgo
Germany	Stift Bethlehem	Ludwigslust
Germany	Otto-Von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	Staedtisches Klinikum Magdeburg	Magdeburg
Germany	Johannes Gutenberg University	Mainz
Germany	Muenchen Onkol. Praxis Elisenhof	Munich
Germany	Kreiskrankenhaus Neustadt A. Rbge. des Landkreises Hannover	Neustadt
Germany	Praxis Innere Medizin	Neustadt
Germany	Klinikum Nurnberg	Nuremberg (Nurnberg)
Germany	Klinikum Ernst Von Bergmann	Postdam
Germany	Klinikum D. Ch. Erxleben	Quedlinburg
Germany	Kreiskrankenhaus Riesa	Riesa
Germany	University of Rostock	Rostock
Germany	Fachkrankenhaus Marienstift	Schwarzenberg
Germany	Katharinenhospital	Stuttgart
Germany	Eberhard Karls Universitaet	Tuebingen
Germany	Klinikum der Universitaet Ulm	Ulm
Germany	Harz-Klinikum Wernigerode GMBH - Medizinische Klinik	Wernigerode
Germany	Klinikum der Stadt Wolfsburg	Wolfsburg
Germany	Gemeinschaftspraxis	Worms
Germany	Medizinische Poliklinik, Universitaet Wuerzburg	Wuerzburg
Germany	Witten University - Klinikum Wuppertal	Wuppertal
Italy	Ospedale San Lazzaro	Alba
Netherlands	Saint Laurentius Ziekenhuis	Roermond
Russian Federation	Russian Academy of Medical Sciences Cancer Research Center	Moscow
South Africa	Medical Oncology Centre of Rosebank	Johannesburg

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Egypt,  France,  Germany,  Italy,  Netherlands,  Russian Federation,  South Africa, 

References & Publications (3)

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 Soc

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.

Köhne CH, van Cutsem E, Wils J, Bokemeyer C, El-Serafi M, Lutz MP, Lorenz M, Reichardt P, Rückle-Lanz H, Frickhofen N, Fuchs R, Mergenthaler HG, Langenbuch T, Vanhoefer U, Rougier P, Voigtmann R, Müller L, Genicot B, Anak O, Nordlinger B; European Organis — View Citation