Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over EORTC-40986 NCT00004885

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.

Entry 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

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

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

Expected Enrollment

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

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.

Köhne CH, van Cutsem E, Wils J, et al.: 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 23 (22): 4856-65, 2005.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Claus-Henning Koehne, MD, Protocol chair(Contact information may not be current)		Ph: 49-381-494-7408 Email: henning.koehne@med.uni-rostock.de

Registry Information
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
Trial Start Date		1999-07-02
Registered in ClinicalTrials.gov		NCT00004885
Date Submitted to PDQ		2000-01-12
Information Last Verified		2007-06-01