Inclusion Criteria

- INCLUSION CRITERIA:

- In the dose escalation cohorts: Patients must have histologically confirmed
malignancy that is metastatic or unresectable and for which standard curative or
palliative measures do not exist or are no longer effective. Histology can be based
on either the primary tumor or metastases.

- In the MTD expansion cohort: Patients must have biopsy proven K-RAS mutant,
metastatic colorectal cancer that has progressed on at least 2 prior standard
therapies. K-RAS mutation status must be verified by a CLIA-certified laboratory.
(NOTE: colorectal patients enrolled during the dose escalation portion do not need to
be K-RAS mutant in order to be eligible).

- Patients must be at least 4 weeks since prior chemotherapy, 6 weeks if the last
regimen included nitrosureas or mitomycin C. Prior radiation is allowed as long as
the radiation was completed 4 weeks prior to study treatment and no more than 35% of
marrow irradiated.

- Age greater than or equal to18 years. Because no dosing or adverse event data are
currently available on the use of AZD6244 in combination with cetuximab in patients
less than 18 years of age, children are excluded from this study, but will be
eligible for future pediatric phase 1 combination trials.

- ECOG performance status less than or equal to 2 (Karnofsky > 60%).

- Life expectancy of greater than 3 months.

- 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

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of
normal (AST and ALT less than or equal to 5.0 X institutional upper limit of
normal will be permitted if liver metastases are present)

- creatinine less than or equal to to to1.5X institution upper limit of normal OR
creatinine clearance greater than or equal to 45 mL/min/1.73 m2, as calculated
by Cockroft-Gault formula, for patients with creatinine levels above
institutional normal. May use a 24 hr. urine collection to determine creatinine
clearance.

- Patients may have received prior cetuximab.

- Patients with brain metastases that have been treated and stable for 2 months will be
eligible for this study.

- Subjects undergoing anti-coagulation therapy with LMWH and warfarin are eligible.
Subjects receiving both warfarin and AZD6244 should have more frequent PT/INR
monitoring (see section 10.0)

EXCLUSION CRITERIA:

- Patients who have had chemotherapy, radiotherapy or hormonal therapy within 4 weeks
(6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who
have not recovered (less than or equal to grade 1) from adverse events due to agents
administered more than 4 weeks earlier.

- Concurrent treatment with an investigational agent other than the investigational
agent(s) used in this study OR treatment within 4 weeks of study entry with any
investigational agent(s) or device(s).

- Failure to recover fully (as judged by the investigator) from prior surgical
procedures.

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

- Patients taking high doses (more than recommended daily dose) of vitamin E will be
excluded. Patients can discontinue use of high dose vitamin E prior to study entry to
be considered eligible.

- Any condition (e.g., gastrointestinal tract disease resulting in an inability to take
oral medication or a requirement for IV alimentation, prior surgical procedures
affecting absorption, or active peptic ulcer disease) that impairs their ability to
swallow and retain AZD6244 capsules.

- Patients with malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel are excluded.
Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or
complete small bowel obstruction are also excluded.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, prior
cardiomyopathy, LVEF less than 50%, unstable angina pectoris, cardiac arrhythmia
(i.e. atrial fibrillation), or psychiatric illness/social situations that would limit
compliance with study requirements.

- Pregnant women are excluded from this study because AZD6244 is a small molecule
kinase inhibitor with the potential for teratogenic or abortifacient effects. Because
there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with AZD6244, breastfeeding should be
discontinued if the mother is treated with AZD6244. These potential risks may also
apply to other agents used in this study.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with AZD6244. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

- Patients who are serologically positive for Hepatitis B or C, or have a history of
liver disease, other forms of hepatitis or cirrhosis are ineligible.

- Use of strong CYP1A2 or 3A4 inducers and/or inhibitors (for example, but not limited
to, ketoconazole, rifampacin, atazanavir, clarithromycin, indinavir, itraconazole,
nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO),
voriconazole, grapefruit or grapefruit juice, ifabutin, rifapentine, phenytoin,
carbamazepine, phenobarbital and St. John's Wort) is not permitted while on study or
within 7 days prior to study enrollment.