Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

OBJECTIVES:

Primary

• Determine the complete response rate in patients with metastatic colorectal cancer treated with cetuximab and FOLFIRINOX chemotherapy comprising oxaliplatin, irinotecan hydrochloride, leucovorin calcium, and fluorouracil as first-line therapy.

Secondary

• Determine the objective response rate in patients treated with this regimen.
• Assess the tolerability of this regimen in these patients.
• Determine the time to response and time to progression in patients treated with this regimen.
• Determine the survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1 and 8. Patients also receive FOLFIRINOX chemotherapy comprising oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 30-90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 15 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Metastatic, unresectable disease
• May or may not express the EGFR gene
• Measurable disease, defined as ≥ 1 measurable lesion by MRI or CT scan

• Lesion must be outside an irradiated area

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Transaminases ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
• Creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No peripheral or symptomatic neuropathy ≥ grade 2 (NCI-CTCAE)
• No complete or partial intestinal blockage
• No intestinal inflammatory disease (e.g., Crohn's disease or ulcerative colitis)
• No chronic diarrhea
• No severe unstable cardiac disease (despite treatment)
• No myocardial infarction within the past 6 months
• No neurological or psychiatric illness, including epilepsy or dementia
• No uncontrolled active infection
• No other prior or concurrent malignancy within the past 5 years except for curatively treated basal cell skin cancer
• No psychological, familial, social, or geographic reason that would preclude study follow-up

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for metastatic disease

• Prior fluorouracil-based adjuvant chemotherapy allowed provided it was administered ≥ 4 weeks ago
• At least 4 weeks since prior and no other concurrent experimental therapy
• No prior irinotecan hydrochloride, oxaliplatin, or monoclonal antibody
• No prior intestinal resection (e.g., hemicolectomy or extended resection of the small intestine)