Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients Following Surgery for Stage III Colorectal Cancer

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00026273

Collaborator

(none)

Locations

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. Combining more than one drug and giving them after surgery may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III 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:

Compare the disease-free survival at 3 years of patients with resected stage III colorectal cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
Compare the disease-free and overall survival at 5 years of patients treated with these regimens.
Compare the safety profiles of these treatment regimens in these patients.
Compare the quality-adjusted survival of patients treated with these regimens.
Correlate the expression of putative prognostic markers (thymidylate synthase, telomerase, topoisomerase) with disease-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

Arm I

Patients receive irinotecan IV over 30-90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 24 hours weekly for 6 weeks. Courses repeat every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
As an alternative schedule, patients may receive irinotecan IV over 30-90 minutes and day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2 every 2 weeks for 6 weeks. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Arm II

Patients receive leucovorin calcium and fluorouracil as in arm I. Quality of life may be assessed at baseline; prior to courses 2, 3, and 4; and at 1, 3, and 6 months.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 1800 patients (900 per arm) will be accrued for this study within 24 months.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter Phase III Open Label Randomized Trial Comparing CPT-11 In Combination With A 5-FU/FA Infusional Regimen To The Same 5-FU/FA Infusional Regimen Alone As Adjuvant Treatment Of Stage III Colon Cancer

Study Start Date :

Jan 1, 2001

Actual Primary Completion Date :

Sep 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon or intraperitoneal rectum
Stage III
Completely resected within the past 3-8 weeks
No gross or microscopic evidence of residual disease after surgery
No rectal cancer requiring total meso-rectal resection or pre- or postoperative radiotherapy
No prior curatively resected synchronous metastasis of colorectal cancer

PATIENT CHARACTERISTICS:

Age:

18 to 75

Performance status:

WHO 0-1

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 2,000/mm^3
Platelet count at least 150,000/mm^3
Hemoglobin at least 10 g/dL

Hepatic:

Bilirubin no greater than upper limit of normal (ULN)
AST and ALT no greater than 2.5 times ULN
Alkaline phosphatase no greater than 2.5 times ULN

Renal:

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min

Cardiovascular:

No myocardial infarction with the past year
No uncontrolled hypertension
No high-risk uncontrolled arrhythmia
No unstable angina pectoris

Other:

HIV negative
No chronic diarrhea
No current chronic inflammation or subobstruction of bowel after surgery
No active uncontrolled infection
No other prior or concurrent malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
No psychological, social, familial, or geographical condition that would preclude follow-up
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior antineoplastic chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

See Disease Characteristics

Surgery:

See Disease Characteristics
No prior celioscopic resection of primary tumor

Other:

At least 30 days since prior participation in another clinical trial with any investigational drug
No other concurrent experimental drugs
No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allgemeines Krankenhaus der Stadt Wien	Vienna (Wien)		Austria	A-1090
2	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
3	National Cancer Institute of Egypt	Cairo		Egypt
4	CHU Pitie-Salpetriere	Paris		France	75651
5	Hopital Tenon	Paris		France	75970
6	Universitats-Krankenhaus Eppendorf	Hamburg		Germany	D-20246
7	Ospedali Riuniti di Bergamo	Bergamo		Italy	24100
8	Universita Degli Studi di Firenze - Policlin. di Careggi	Firenze (Florence)		Italy	1 (50-134)
9	Ospedale San Carlo Borromeo	Milano (Milan)		Italy	20153
10	Azienda Ospedaliera S. Maria	Terni		Italy	05100
11	Universita Degli Studi di Udine	Udine		Italy	33100
12	Instituto Portugues de Oncologia do Porto	Porto		Portugal	4200
13	Hospital Universarito "Reina Sofia"	Cordoba		Spain	14004
14	Hopital Cantonal Universitaire de Geneva	Geneva		Switzerland	CH-1211
15	Royal Marsden Hospital	Sutton	England	United Kingdom	SM2 5PT