Capecitabine and Oxaliplatin With or Without Cetuximab in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

• Compare the efficacy of capecitabine and oxaliplatin with vs without cetuximab in patients with epidermal growth factor receptor-positive metastatic unresectable colorectal cancer.
• Compare the objective response (complete and partial response) in patients treated with these regimens.

Secondary

• Compare the safety of these regimens in these patients.
• Compare the clinical benefit (complete response, partial response, or stable disease for at least 18 weeks) in patients treated with these regimens.
• Compare overall survival, time to progression, and time to treatment failure in patients treated with these regimens.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), type of metastases (synchronous vs metachronous), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1.
• Arm II: Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8.

In both arms, courses repeat every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients will be followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 74 patients (37 per treatment arm) will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic colorectal cancer

• Unresectable disease
• Primary tumor or metastases must be epidermal growth factor receptor-positive by immunohistochemistry
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by CT scan

• Measurable lesion must not be in a previously irradiated area
• No prior or current CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal

Renal

• Creatinine clearance > 50 ml/min

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No symptomatic coronary artery disease
• No uncontrolled cardiac arrhythmia
• No myocardial infarction within the past 12 months
• No other significant cardiac disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation
• Negative pregnancy test
• No peripheral neuropathy of any origin > grade 1 (e.g., alcohol or diabetes)
• No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication
• No severe reaction attributed to fluoropyrimidine therapy
• No known hypersensitivity to fluorouracil or any other component of the trial drugs
• No known dihydropyrimidine dehydrogenase deficiency
• No other medical condition (e.g., uncontrolled diabetes or active autoimmune disease), geographical situation, or psychiatric disorder that would preclude study compliance
• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for advanced or metastatic cancer
• At least 6 months since prior adjuvant chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 30 days since prior experimental drugs
• No other concurrent experimental drugs
• No concurrent drugs that are contraindicated for use with the trial drugs
• No other concurrent anticancer therapy
• No concurrent sorivudine or any of its chemically-related analogues (e.g., lamivudine)