FOLFIRI or FOLFOX With or Without Cetuximab in Patients With Metastatic Adenocarcinoma of the Colon or Rectum

1. Locally Advanced or Metastatic Colorectal Cancer * Eligible patients must have histologically or cytologically documented locally advanced or metastatic colorectal cancer. The site of the primary lesion must be or have been confirmed endoscopically, surgically or radiologically to have been in the large bowel. * Patients with a history of colorectal cancer treatment by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless: * Either an interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease OR * The primary cancer was stage I. * Clinicians should consider biopsy of lesions to establish the diagnosis of metastatic colorectal cancer in each case if there is substantial clinical ambiguity regarding the nature or source of apparent metastases. 2. No prior treatment for advanced or metastatic colorectal cancer * Patients may have received prior adjuvant chemotherapy (no more than 6 months or 4 cycles) or radiation with radiosensitizing chemotherapy. The last course of chemotherapy must have concluded \> 12 months prior to registration. Patients may not have previously received irinotecan ≤ or oxaliplatin therapy in either the adjuvant or metastatic setting. No concurrent use of additional investigational agents is allowed while participating in this study. 3. Patients may not have had prior radiotherapy to greater than 25% of bone marrow. Standard adjuvant rectal cancer chemoradiation will not exclude the patient from protocol entry. Radiation must have concluded ≥ 4 weeks from registration. 4. Patients should have completed any major surgery ≥ 4 weeks from registration. Patients must have completed any minor surgery ≥ 2 weeks from registration. Patients must have fully recovered from the procedure. Insertion of a vascular access device is not considered major or minor surgery. 5. No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years. 6. Age ≥ 18 years 7. CTC (ECOG) performance status of 0-1. 8. No evidence of Gilbert's syndrome - Patients with Gilbert's Syndrome may have a greater risk of irinotecan toxicity due to the abnormal glucuronidation of SN-38. Evidence of Gilbert's Syndrome would include a prior finding of an isolated elevation of indirect bilirubin. 9. Patients must have at least one paraffin block available or appropriate number of unstained slides for analysis of EGFR status. 10. No symptomatic sensory peripheral neuropathy of ≥ grade II at baseline. 11. Non-pregnant and non-lactating * Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG within 72 hours prior to initiation of treatment. This is because DNA alkylating agents are known to be teratogenic, and the effects of irinotecan, OXAL, 5-FU and C225 on a developing fetus at the recommended therapeutic doses are unknown. * Women of child bearing potential includes: * any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or * is not postmenopausal \[defined as amenorrhea ≥ 12 consecutive months\] or * women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL * women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), should be considered to be of child bearing potential. * Should a woman become pregnant or suspect she is pregnant while participating on on this study, she should inform her physician immediately. Because the risk of toxicity of these agents in nursing infants is also unknown, breastfeeding should be discontinued. 12. No known central nervous system metastases or carcinomatous meningitis. 13. No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung. 14. No pleural effusion or ascites that causes ≥ grade 2 dyspnea. 15. No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of \> 3 watery or soft stools daily in patients without a colostomy or ileostomy. Patients with a colostomy or ileostomy may be entered at investigator discretion. 16. No prior exposure or known sensitivity to chimerized or murine antibodies, C225 (or other EGFR inhibitors) or any tyrosine kinase inhibitors 17. No significant history of cardiac disease, such as unstable angina, CHF, MI, stroke or a LVEF below the institutional range of normal on a baseline multiple gated acquisition (MUGA) or echocardiogram. 18. Patients must not have an uncontrolled seizure disorder, or active neurological disease. 19. Patients may not have received itraconazole or ketoconazole less than 4 weeks prior to registration. 20. Required Initial Laboratory Values: * Granulocytes ≥ 1500/ µl * Hemoglobin ≥ 9.0 gram/dL (patient may be transfused to meet this criterion) * Platelet count ≥ 100,000/ µl * Creatinine ≤ 1.5 x Upper limits of normal (ULN) * Bilirubin ≤ 1.5 mg/dL * AST ≤ 5.0 x ULN * Albumin ≥ 2.5 gram/dL