Inclusion Criteria

- INCLUSION CRITERIA:

- Patients must have histologically or cytologically confirmed locally advanced,
non-metastatic adenocarcinoma of the rectum (clinical stage T3 anyN, T4 anyN, or AnyT
N+).

- Patients with recurrent adenocarcinoma of the rectum with no clinically evident
distant disease will be eligible if they are deemed to have pelvic nodal metastases
or disease extending through the muscularis of the rectum. These patients should be
evaluated by a Radiation Oncologist, Medical Oncologist and Surgeon prior to
enrolling on study to confirm anticipated resectability. These patients should not
have received prior radiotherapy for management of their rectal cancer.

- Age greater than or equal to 18 years.

- ECOG performance status less than or equal to 1 (Karnofsky greater than or equal to
70%).

- Patients must have normal organ and marrow function as defined below:

- leukocytes greater than or equal to 3,000/mcL

- absolute neutrophil count greater than or equal to 1,500/mcL

- platelets: greater than or equal to 100,000/mcL

- total bilirubin: within normal institutional limits except for patients with
Gilbert's who must have a direct bilirubin of less than 1.0 mg/dL

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times the institutional upper
limit of normal

- creatinine within normal institutional limits

OR

-- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with
creatinine levels above institutional normal.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for six months after the completion of
radiation. Women of child-bearing potential must have a negative pregnancy test prior
to entry. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
Adequate contraception for male patients should be used for 6 months after
irradiation.

- Ability to understand and the willingness to sign a written informed consent
document.

- Willingness to sign a release of medical records pertaining to previous and future
treatment for rectal cancer.

EXCLUSION CRITERIA:

- Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
prior to entering the study or lack of recovery from adverse events due to agents
administered more than 4 weeks earlier.

- Patients may not be receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AZD6244 or other agents used in study.

- Previous MEK inhibitor use.

- Contraindications to radiotherapy to the pelvis such as inflammatory bowel disease or
known genetic sensitivity to ionizing radiation such as ataxia telengiectasia.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients with QTc interval greater than 470 msecs or other factors that increase the
risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia,
family history of long QT interval syndrome) including heart failure that meets New
York Heart Association (NYHA) class III and IV definitions are excluded.

- Required use of a concomitant medication that can prolong the QT interval. A
comprehensive list of agents with the potential to cause QTc prolongation can be
found at http://www.arizonacert.org/medical-pros/drug-lists/drug-lists.htm.

- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
bowel disease), or significant bowel resection that would preclude adequate
absorption.

- HIV-positive patients on combination antiretroviral therapy.

- Known dihydropyrimidine dehydrogenase deficiency.

- History of prior radiation to the pelvis

- For patients with newly diagnosed rectal cancer, prior therapy for adenocarcinoma of
the rectum with the exception of diverting colostomy if required to relieve
obstruction (including chemotherapy).

- Patients with recurrent rectal cancer may not have undergone prior radiotherapy for
rectal adenocarcinoma or have received therapy for the recurrence with the exception
of diverting colostomy if required to relieve obstruction.

- History of myocardial infarction within the past 6 months or history of ventricular
arrhythmia

- Uncontrolled hypertension

- Pregnant or lactating females are excluded