• Response rate for the combination treatment
  

• Toxicity rates
  
• Time to progression
  
• Survival
  

The current treatment options for metastatic colon cancer are in need of further improvement. The three-drug combination of oxaliplatin with 5-FU/LV in the second-line treatment of metastatic colorectal cancer have shown a significant increase in response rate compared to 5-FU/LV alone. Oxaliplatin has recently been FDA-approved for this indication and is now a standard first-line agent in combination with a fluoropyrimidine. Cetuximab, a chimeric monoclonal antibody against the growth factor receptor, has shown activity with and without irinotecan in subjects with colorectal cancer refractory to irinotecan alone. Cetuximab has also been shown to be safe and effective when administered with infusional 5-FU/folinic acid plus irinotecan. These results suggest that the addition of cetuximab to fluoropyrimidine/oxaliplatin-based regimen in the 1st line setting should be explored. The use of the oral fluoropyrimidine, capecitabine, to replace infusional 5FU has been widely used for improved convenience and possible safety. We have chosen a modified biweekly CapeOx regimen due to its improved tolerance and response rate with a fixed dose of capecitabine given its widespread practice and ease of use.

Inclusion Criteria:

Inclusion:

1. Histologically confirmed advanced adenocarcinoma of the colon or rectum
2. Measurable disease by RECIST criteria
3. Tumor tissue available for IHC testing for EGFr expression
4. ECOG Performance Status 0-1
5. Recovery in full from any previous surgical procedure
6. Expected survival greater than 12 weeks
7. Subjects 18 years of age or older
8. Absolute neutrophil count (ANC) > 1,500/mm3
9. Platelet count > 100,000/mm3
10. Serum creatinine level > 1.5 times the ULN

Exclusion Criteria:

1. Prior chemotherapy for metastatic disease. Prior adjuvant therapy with 5FU/LV or Irinotecan plus 5FU/LV allowed if completed at least six months prior to entering study
2. Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy and women who are pregnant and breastfeeding
3. Subjects with > Grade 1 neuropathy
4. Subjects with any active or uncontrolled infection
5. History of myocardial infarction within the previous six months or current clinical evidence of congestive heart failure
6. History of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that cancer for at least 5 years
7. Central nervous system metastases
8. Prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA)
9. Subjects receiving a prior investigational agent within 30 days
10. Prior therapy with oxaliplatin, cetuximab, or prior therapy that targets the EGFr pathway