RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill
them or deliver tumor-killing substances to them without harming normal cells. Drugs used in
chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
die. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor
PURPOSE: Phase II trial to study the effectiveness of combining cetuximab with combination
chemotherapy in treating patients who have stage IV colorectal cancer.
OBJECTIVES: I. Determine the safety profile of cetuximab, irinotecan, leucovorin calcium,
and fluorouracil in patients with stage IV colorectal cancer. II. Determine the response
rate and time to progression in patients treated with this regimen.
OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours once
weekly on weeks 1-6. Patients also receive irinotecan IV over 90 minutes, leucovorin calcium
IV over 10-15 minutes, and fluorouracil IV over 3-5 minutes once weekly on weeks 1-4.
Treatment repeats every 6 weeks in the absence of disease progression or unacceptable
toxicity. Patients are followed at 1 month and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 2 months.
DISEASE CHARACTERISTICS: Histologically confirmed stage IV colorectal cancer Any T, any N,
M1 Immunohistochemical evidence of epidermal growth factor receptor expression (at least
1+) Bidimensionally measurable metastatic disease Meningeal or CNS involvement by tumor
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: WBC at least 3,500/mm3 Granulocyte count at least 1,500/mm3
Platelet count at least 150,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin normal
AST no greater than 5 times upper limit of normal (ULN) Renal: Creatinine no greater than
1.5 times ULN Cardiovascular: No history of uncontrolled angina, arrhythmias, or
congestive heart failure Neurologic: No uncontrolled seizure disorder No active
neurological disease No grade 2 or greater neuropathy Other: No other malignancy within
the past 3 years except basal cell skin cancer or pre-invasive carcinoma of the cervix No
medical or psychiatric condition that would preclude study Not pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior murine monoclonal antibody therapy No
prior cetuximab Chemotherapy: No prior chemotherapy for metastatic disease Prior adjuvant
chemotherapy for stage I, II, or III colorectal cancer allowed only if disease-free for
more than 1 year from completion of therapy until the first evidence of metastatic disease
No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior
radiotherapy for metastatic disease No concurrent radiotherapy Surgery: At least 3 weeks
since prior surgery (excluding prior diagnostic biopsy) Other: No prior treatment for
metastatic colorectal cancer At least 30 days since prior investigational agents