A Phase III Trial Of Irinotecan /5-FU/ Leucovorin Or Oxaliplatin /5-FU / Leucovorin With And Without Cetuximab (C225) For Patients With Untreated Metastatic Adenocarcinoma Of The Colon or Rectum

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed metastatic colorectal adenocarcinoma

- Primary site of disease in the large bowel as determined endoscopically,
surgically, or radiologically

- Histologic or cytologic confirmation is not required for recurrent metastatic
disease in patients with prior colorectal cancer treated with surgery unless
either of the following criteria are met:

- More than 5 years have elapsed between the prior primary surgery and the
development of metastatic disease

- Primary cancer was stage I

- Tumor tissue available for epidermal growth factor receptor (EGFR) status analysis

- No pleural effusion or ascites that causes grade 2 or greater dyspnea

- No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusion allowed)

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 mg/dL

- AST ≤ 5.0 times upper limit of normal (ULN)

- Albumin ≥ 2.5 g/dL

- No evidence of Gilbert's syndrome

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No unstable angina

- No congestive heart failure

- No prior myocardial infarction

- No prior stroke

- No other significant cardiac disease

- LVEF ≥ normal by echocardiogram or MUGA

Pulmonary

- No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung

Neurologic

- No uncontrolled seizure disorder

- No Temporarily closed neurological disease

- No symptomatic sensory peripheral neuropathy grade 2 or greater

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No predisposing uncontrolled colonic or small bowel disorder as evidenced by > 3
watery or soft stools daily at baseline*

- No known sensitivity to chimerized or murine antibodies, cetuximab or other EGFR
inhibitors, or tyrosine kinase inhibitors

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix NOTE: *In patients
without a colostomy or ileostomy; patients with a colostomy or ileostomy are eligible
at the discretion of the investigator

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic therapy for metastatic colorectal cancer

- No prior chimerized or murine antibodies

- No prior cetuximab

- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

- See Radiotherapy

- More than 12 months since prior chemotherapy

- No prior chemotherapy for metastatic colorectal cancer

- No prior irinotecan or oxaliplatin in the adjuvant or metastatic setting

- No more than 6 months or 4 courses of prior adjuvant chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- No prior endocrine therapy for metastatic colorectal cancer

- No concurrent hormonal therapy except the following:

- Steroids for adrenal failure

- Hormones administered for non-disease-related conditions (e.g., insulin for
diabetes)

- Intermittent use of dexamethasone as an antiemetic

Radiotherapy

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy for metastatic colorectal cancer

- No prior radiotherapy to more than 25% of bone marrow

- Prior standard adjuvant chemoradiotherapy for rectal cancer allowed

- Prior adjuvant radiotherapy with radiosensitizing chemotherapy allowed

- No concurrent palliative radiotherapy except whole brain radiotherapy for documented
CNS disease

Surgery

- See Disease Characteristics

- More than 4 weeks since prior major surgery*

- More than 2 weeks since prior minor surgery* and recovered

- No prior surgery for metastatic colorectal cancer NOTE: *Insertion of a vascular
device is not considered major or minor surgery

Other

- At least 4 weeks since prior itraconazole or ketoconazole

- No other prior treatment for metastatic colorectal cancer

- No prior EGFR inhibitors

- No prior tyrosine kinase inhibitors

- No other concurrent investigational agents

- No concurrent agents to minimize neurotoxicity of oxaliplatin (e.g., carbamazepine,
magnesium, or calcium)