Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the rectum that begins within 15cm of the
anal verge as determined by sigmoidoscopy and/or colonoscopy, with no evidence of
distant metastatic disease. A complete colonoscopy to the cecum is recommended prior
to initiating protocol therapy.

- Staging with transrectal ultrasound or endorectal coil MRI to confirm clinical stage
of T3 or T4 or lymph node positive rectal adenocarcinoma

- Tumor is K-ras wildtype by method of choice at respective institution (testing codons
12 and 13)

- Performance status: ECOG less than or equal to 2

- 18 years of age or older

- No evidence of metastatic disease by abdominal/pelvic CT and chest imaging

- Adequate bone marrow, renal,and hepatic function as outlined in protocol

- All patients will be evaluated by a surgeon and considered a candidate for definitive
surgery

- Coumadin or heparin management for line care of other indications is permitted. The
INR will be monitored weekly in patients taking coumadin.

Exclusion Criteria:

- Prior treatment for this malignancy

- Prior history of pelvic radiation therapy

- Prior history of 5-FU based or EGFR receptor inhibitor therapy

- Prior history of an allergic reaction to a monoclonal antibody

- Uncontrolled serious medical or psychiatric illness

- Significant history of uncontrolled cardiac disease

- Sexually active women of childbearing potential must use an effective method of birth
control during the course of the study

- Unwilling to agree to pre and post-cetuximab sigmoidoscopy and biopsy