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

Federation Francophone de Cancerologie Digestive

Status and phase

Unknown

Phase 3

Conditions

Colorectal Cancer

Treatments

Procedure: adjuvant therapy

Drug: leucovorin calcium

Drug: FOLFIRI regimen

Drug: irinotecan hydrochloride

Drug: fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT00091312

CDR0000387797

EORTC-40012

PETACC-4

FFCD-EORTC-40012

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,976 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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