Pre-op Rectal ChemoRad +/- Cetuximab

Rectal cancer remains a significant cause of morbidity and mortality in the United States.
Standard treatment for patients with locally advanced rectal cancer generally includes
combined chemotherapy and radiotherapy administered either before (neoadjuvant) or after
(adjuvant) definitive surgical resection. Published data from Germany has suggested
advantages to a neoadjuvant strategy. Currently, the standard concurrent chemoradiotherapy
regimen in the United States is pelvic irradiation administered concurrently with
5-fluorouracil (5-FU) given as a protracted venous infusion. However, local recurrence
remains a problem. Recently completed randomized trials of chemoradiotherapy have
demonstrated local recurrence rates between 8-17% even with currently accepted standard
chemoradiotherapy and adequate surgical management.

Several recent trials have explored the use of radiotherapy and cetuximab with good results.

Because of the non-overlapping toxicity profiles and the potentially diverse and
complimentary mechanisms of action, the combination of chemotherapy plus ERBITUX given
concurrently with pelvic radiotherapy may improve on the outcomes seen with current
standards for patients with locally advanced adenocarcinoma of the rectum.

Inclusion Criteria:

Note: Please see Section 8.1 for the necessary "Prestudy Assessments".

A patient will be eligible for inclusion in this study if s/he meets all of the following
criteria:

- Has a histologically confirmed diagnosis of newly diagnosed adenocarcinoma of the
rectum (tumor within 15 cm of the anal verge). Location of tumor (lower 1/3rd vs.
middle or upper 1/3rd) and pre-treatment nodal status (N0 vs. N1 or N2) will be
recorded in the eCRF. Patients with only non-measurable disease are eligible as long
as they meet the other disease requirements in this criterion as well as all other
eligibility criteria.

- Has tumor that is locally advanced (T3/T4 or lymph node positive) by preoperative
assessment with CT or MRI imaging or transrectal ultrasonography.

- Has no evidence of distant metastases by radiographic staging

- Has an ECOG Performance Status (PS) 0-1

- Is greater than 18 years of age

- Has adequate marrow and organ system function as assessed by the following lab
values:

White blood cell (WBC) count See protocol for specific details Absolute neutrophil count
(ANC) See protocol for specific details Hemoglobin See protocol for specific details Total
bilirubin See protocol for specific details AST and ALT See protocol for specific details
Serum creatinine See protocol for specific details Platelet count See protocol for
specific details

- Sexually active women of childbearing potential must use an effective method of birth
control during the course of the study, in a manner such that risk of failure is
minimized.

Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the
importance of avoiding pregnancy during trial participation and the potential risk factors
for an unintentional pregnancy. In addition, men enrolled on this study should understand
the risks to any sexual partner of childbearing potential and should practice an effective
method of birth control.

All WOCBP MUST have a negative pregnancy test within 3 weeks prior to registration
(confirmed within 7 days prior to first receiving investigational product). If the
pregnancy test is positive, the patient must not receive investigational product and must
not be enrolled in the study.

In addition, all WOCBP should be instructed to contact the Investigator immediately if
they suspect they might be pregnant (eg, missed or late menstrual period) at any time
during study participation.

The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a
patient participating in the study.

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form

Exclusion Criteria:

- A patient will be excluded from this study if s/he meets any of the following
criteria:

- Has another disease similar to one being studied (ie, colon cancer)

- Has evidence of distant metastases by radiographic staging

- Has had prior treatment for the current disease

- Has had prior stem cell or bone marrow transplant or any organ transplant with the
exception of corneal transplant or cadaver bone graft

- Has a history of hypersensitivity to any of study treatments

- Has had a prior severe infusion reaction to a monoclonal antibody

- Has received prior therapy, at any time, which specifically and directly targets the
EGFR pathway

- Has a significant history of uncontrolled cardiac disease; ie, uncontrolled
hypertension, unstable angina, recent myocardial infarction (within prior 6 months),
uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection
fraction

- Has evidence of CNS involvement (CNS imaging is not required for study enrollment
unless clinically suspected CNS disease is present.)

- Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious infection or Gilbert's Syndrome

- Has a history of other malignancy within the last 5 years (except cured basal cell
carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the
diagnosis or assessment of any of the study drugs. Patients, who have received prior
radiotherapy to any regional site other than the pelvis, as long as all other
inclusion criteria are met, could be considered for enrollment after discussion with
Dr. McCollum.

- Is a pregnant or nursing woman

- Is unable to comply with requirements of study