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Fluorouracil and Irinotecan With or Without Leucovorin Compared With Observation in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

Primary Purpose

Colorectal Cancer

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
FOLFIRI regimen
fluorouracil
irinotecan hydrochloride
leucovorin calcium
adjuvant therapy
Sponsored by
Federation Francophone de Cancerologie Digestive
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II colon cancer, adenocarcinoma of the colon

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon Stage II disease (pT3, N0 or pT4, N0) Penetration of the subserosa or serosa No lymph node metastases At least 12 lymph nodes analyzed More than 1 synchronous primary colon tumor allowed Staging determined for the more advanced tumor Curative radical resection within the past 2-8 weeks required Proximal, distal, and radical margins must be free of tumor (R0 resection) No rectal tumors Gross distal margin of the primary tumor must lie above the peritoneal reflection No known familial adenomatous polyposis No hereditary nonpolyposis colorectal cancer No distant metastases PATIENT CHARACTERISTICS: Age 18 to 75 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 2,000/mm^3 Platelet count ≥ 100,000mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin < 1.25 times upper limit of normal (ULN) No known Gilbert's syndrome Renal Creatinine < 1.25 times ULN Cardiovascular No severe or uncontrolled coronary disease No severe heart failure No uncontrolled arterial hypertension No myocardial infarction within the past year No cerebral vascular accident within the past year Cardiac arrhythmia allowed provided patient is on proper anticoagulation therapy* NOTE: *Aspirin is not considered proper anticoagulation Gastrointestinal No Gardner's syndrome No Turcot's syndrome No Crohn's disease No ulcerative colitis Other No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No other serious disease No contraindication to any study drugs No known allergy to leucovorin calcium Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 6 months after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other No other concurrent anticancer therapy No concurrent vitamin supplements containing folic acid

Sites / Locations

  • National Cancer Institute - Cairo
  • Centre Hospitalier Universitaire Ambroise Pare - Boulogne
  • Hopital Du Bocage
  • Medizinische Klinik I
  • Ospedali Riuniti di Bergamo
  • Azienda Ospedaliero Careggi
  • Universita Degli Studi di Florence - Policlinico di Careggi
  • Instituto Portugues de Oncologia Centro do Porto, S. A.
  • Hospital Universitario de Elche

Outcomes

Primary Outcome Measures

Disease-free survival at 5 years

Secondary Outcome Measures

Overall survival at 8 years
Tolerability
Correlation of clinical, histological, and biological prognostic factors with outcome

Full Information

First Posted
September 7, 2004
Last Updated
February 6, 2009
Sponsor
Federation Francophone de Cancerologie Digestive
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1. Study Identification

Unique Protocol Identification Number
NCT00091312
Brief Title
Fluorouracil and Irinotecan With or Without Leucovorin Compared With Observation in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
Official Title
Randomized Phase III Intergroup Trial in Resected Stage 2 (Dukes B) Colon Cancer: 6-Month Infusional 5FU-CPT11 (+/- Folinic Acid) Versus Observation - Determination of Biologic Predictive and Response Factors
Study Type
Interventional

2. Study Status

Record Verification Date
December 2006
Overall Recruitment Status
Unknown status
Study Start Date
June 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Federation Francophone de Cancerologie Digestive

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in 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 any remaining tumor cells. It is not yet known whether combination chemotherapy is more effective than observation alone in treating patients who have undergone surgery for colon cancer. PURPOSE: This randomized phase III trial is studying irinotecan and fluorouracil with or without leucovorin to see how well they work compared to observation alone in treating patients who have undergone surgery for stage II colon cancer.
Detailed Description
OBJECTIVES: Primary Compare 5-year disease-free survival in patients with resected stage II adenocarcinoma of the colon treated with adjuvant chemotherapy comprising fluorouracil and irinotecan with or without leucovorin calcium vs no adjuvant therapy. Secondary Compare 8-year overall survival in patients treated with these regimens. Compare tolerability of these regimens in these patients. Correlate clinical, histological, and biological prognostic factors with outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (pT3 vs pT4), pathological differentiation (poorly or undifferentiated vs well or moderately differentiated), and microsatellite instability (positive vs negative vs unknown). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients are further randomized to receive 1 of 3 adjuvant chemotherapy regimens. Regimen A: Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1, 15, and 29. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Regimen B: Patients receive irinotecan IV over 30-90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 24 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Regimen C: Patients receive irinotecan IV over 60 minutes followed by fluorouracil IV continuously over 48 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients undergo observation only. Patients are followed every 6 months. PROJECTED ACCRUAL: A total of 1,976 patients (988 per treatment arm [247 each in regimens A and B of arm I and 494 in regimen C of arm I]) will be accrued for this study within 4.5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage II colon cancer, adenocarcinoma of the colon

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
1976 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
FOLFIRI regimen
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Primary Outcome Measure Information:
Title
Disease-free survival at 5 years
Secondary Outcome Measure Information:
Title
Overall survival at 8 years
Title
Tolerability
Title
Correlation of clinical, histological, and biological prognostic factors with outcome

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon Stage II disease (pT3, N0 or pT4, N0) Penetration of the subserosa or serosa No lymph node metastases At least 12 lymph nodes analyzed More than 1 synchronous primary colon tumor allowed Staging determined for the more advanced tumor Curative radical resection within the past 2-8 weeks required Proximal, distal, and radical margins must be free of tumor (R0 resection) No rectal tumors Gross distal margin of the primary tumor must lie above the peritoneal reflection No known familial adenomatous polyposis No hereditary nonpolyposis colorectal cancer No distant metastases PATIENT CHARACTERISTICS: Age 18 to 75 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 2,000/mm^3 Platelet count ≥ 100,000mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin < 1.25 times upper limit of normal (ULN) No known Gilbert's syndrome Renal Creatinine < 1.25 times ULN Cardiovascular No severe or uncontrolled coronary disease No severe heart failure No uncontrolled arterial hypertension No myocardial infarction within the past year No cerebral vascular accident within the past year Cardiac arrhythmia allowed provided patient is on proper anticoagulation therapy* NOTE: *Aspirin is not considered proper anticoagulation Gastrointestinal No Gardner's syndrome No Turcot's syndrome No Crohn's disease No ulcerative colitis Other No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No other serious disease No contraindication to any study drugs No known allergy to leucovorin calcium Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 6 months after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other No other concurrent anticancer therapy No concurrent vitamin supplements containing folic acid
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurent Bedenne, MD
Organizational Affiliation
Hopital Du Bocage
Official's Role
Study Chair
Facility Information:
Facility Name
National Cancer Institute - Cairo
City
Cairo
Country
Egypt
Facility Name
Centre Hospitalier Universitaire Ambroise Pare - Boulogne
City
Boulogne Billancourt
ZIP/Postal Code
F-92104
Country
France
Facility Name
Hopital Du Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Medizinische Klinik I
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Ospedali Riuniti di Bergamo
City
Bergamo
ZIP/Postal Code
24100
Country
Italy
Facility Name
Azienda Ospedaliero Careggi
City
Florence
ZIP/Postal Code
50139
Country
Italy
Facility Name
Universita Degli Studi di Florence - Policlinico di Careggi
City
Florence
ZIP/Postal Code
50139
Country
Italy
Facility Name
Instituto Portugues de Oncologia Centro do Porto, S. A.
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Hospital Universitario de Elche
City
Elche Alicante
ZIP/Postal Code
E-03203
Country
Spain

12. IPD Sharing Statement

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Fluorouracil and Irinotecan With or Without Leucovorin Compared With Observation in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

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