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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00004885

Collaborator

(none)

430

Enrollment

Locations

7.5

Patients Per Site

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jul 1, 1999

Actual Primary Completion Date :

Jul 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Allgemeines Krankenhaus der Stadt Wien	Vienna	Austria	A-1090
2	U.Z. Gasthuisberg	Leuven	Belgium	B-3000
3	National Cancer Institute of Egypt	Cairo	Egypt
4	Institut Gustave Roussy	Villejuif	France	F-94805
5	PZB - Praxenzentrum	Aachen	Germany	D-52062
6	Kreiskrankenhaus Aurich	Aurich	Germany	D-26603
7	Haematology-Oncology	Braunschweig	Germany	D-38100
8	Humaine Klinik Dresden GmbH	Dresden	Germany	01326
9	Medizinische Klinik I	Dresden	Germany	D-01307
10	Universitaetsklinik Duesseldorf	Duesseldorf	Germany	D-40225
11	St. Johannes Hospital - Medical Klinik II	Duisburg	Germany	D-47166
12	Hans-Susemihl-Krankenhaus	Emden	Germany	D-26721
13	Haemato-Onkol. Praxis	Essen	Germany	45127
14	Universitaetsklinik und Strahlenklinik - Essen	Essen	Germany	D-45122
15	Kliniken Essen-Mitte	Essen	Germany	D-45136
16	Klinikum Frankfurt (Oder)	Frankfurt (Oder)	Germany	D-15236
17	Klinikum der J.W. Goethe Universitaet	Frankfurt	Germany	D-60590
18	Klinik Fuer Innere Medizin Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald	Germany	D-17487
19	Marien Hospital	Hagen	Germany	58095
20	Allgemeines Krankenhaus Hagen	Hagen	Germany	D-58095
21	Martin Luther Universitaet	Halle Saale	Germany	DOH-0-6112
22	Internistisch - Onkologische Gemeinschaftspraxis	Halle	Germany	D-06110
23	Hermann-Holthusen Institute for Radiotherapy	Hamburg	Germany	D-20099
24	Haematologisch-Onkologische Praxis Altona	Hamburg	Germany	D-22765
25	Evangelische Krankenhaus Hamm	Hamm	Germany	DOH-5-9063
26	Henriettenstiftung - Chirurgische Klinik	Hannover	Germany	D-30171
27	Krankenhaus Siloah - Medizinische Klinik II	Hannover	Germany	D-30449
28	Medizinische Hochschule Hannover	Hannover	Germany	D-30625
29	Marienhospital/Ruhr University Bochum	Herne	Germany	DOH-4-4625
30	Universitatsklinik, Saarland	Homburg/Saar	Germany	D-66421
31	Haematologisch-Oncologische Praxis	Koblenz	Germany	D-56068
32	Klinikum Lippe-Lemgo	Lemgo	Germany	D-32657
33	Stift Bethlehem	Ludwigslust	Germany	D-19288
34	Staedtisches Klinikum Magdeburg	Magdeburg	Germany	D-39002
35	Otto-Von-Guericke-Universitaet Magdeburg	Magdeburg	Germany	D-39120
36	Johannes Gutenberg University	Mainz	Germany	D-55131
37	Muenchen Onkol. Praxis Elisenhof	Munich	Germany	D-80335
38	Praxis Innere Medizin	Neustadt	Germany	D-01844
39	Kreiskrankenhaus Neustadt A. Rbge. des Landkreises Hannover	Neustadt	Germany	D-31533
40	Klinikum Nurnberg	Nuremberg (Nurnberg)	Germany	D-90419
41	Klinikum Ernst Von Bergmann	Postdam	Germany	D-14467
42	Klinikum D. Ch. Erxleben	Quedlinburg	Germany	D-06484
43	Kreiskrankenhaus Riesa	Riesa	Germany	D-01589
44	University of Rostock	Rostock	Germany	18057
45	Fachkrankenhaus Marienstift	Schwarzenberg	Germany	D-08340
46	Katharinenhospital	Stuttgart	Germany	D-70174
47	Eberhard Karls Universitaet	Tuebingen	Germany	D-72076
48	Klinikum der Universitaet Ulm	Ulm	Germany	D-89081
49	Harz-Klinikum Wernigerode GMBH - Medizinische Klinik	Wernigerode	Germany	D-38843
50	Klinikum der Stadt Wolfsburg	Wolfsburg	Germany	D-38440
51	Gemeinschaftspraxis	Worms	Germany	DOH-6-7547
52	Medizinische Poliklinik, Universitaet Wuerzburg	Wuerzburg	Germany	D-97070
53	Witten University - Klinikum Wuppertal	Wuppertal	Germany	D-42283
54	Ospedale San Lazzaro	Alba	Italy	12051
55	Saint Laurentius Ziekenhuis	Roermond	Netherlands	6043 CV
56	Russian Academy of Medical Sciences Cancer Research Center	Moscow	Russian Federation	115478
57	Medical Oncology Centre of Rosebank	Johannesburg	South Africa	2193