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
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival at 5 years
Safety Issue:
No
Principal Investigator
Laurent Bedenne, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Hopital Du Bocage
Authority:
United States: Federal Government
Study ID:
CDR0000387797
NCT ID:
NCT00091312
Start Date:
June 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage II colon cancer
- adenocarcinoma of the colon
- Colonic Neoplasms
- Colorectal Neoplasms
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