Selumetinib in Cancers With BRAF Mutations

Inclusion Criteria:

* Ability to understand and willingness to sign a written informed consent document
* Histologically confirmed metastatic or unresectable solid tumor
* Results from tumor tissue analysis that show a glutamic acid-for-valine substitution at amino acid position 600 in the BRAF gene (V600E) or other activating BRAF mutation, as determined by high-throughput genotyping
* Patients may have received any number of prior systemic treatments for their cancer
* At least one measurable site of disease by CT, according to standard RECIST criteria 1.0
* ECOG performance status 0-1
* Absolute neutrophil count \> 1500 per cubic mm
* Platelet count \> 100,000 per cubic mm
* Hemoglobin \> 9 g/dl
* Serum bilirubin \< 1.5 x upper limit of normal
* Serum AST and ALT \< 2.5 x upper limit of normal (=\< 5 x upper limit of normal, for liver metastases)
* Serum creatinine \< 1.5 x upper limit of normal
* For women of childbearing potential, negative serum pregnancy test and use of physician-approved method of birth control throughout the study

Exclusion Criteria:

* Estimated life expectancy \> 12 weeks
* Patients with melanoma
* Have received chemotherapy or radiotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C), or a targeted therapy within 2 weeks prior to entering the study
* Have not recovered from adverse events due to agents previously administered (CTCAE v3 grade 1 or baseline)
* Currently receiving other investigational agents
* Known brain metastases, unless treated and stable off of corticosteroids for at least four weeks
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
* Prior treatment with a selective inhibitor of RAF or MEK (e.g., RAF265); (note: prior sorafenib is allowed)
* Uncontrolled intercurrent illness, including but not limited to:

  * Clinically significant active infection
  * Symptomatic congestive heart failure, unstable angina pectoris, and/or cardiac arrhythmia other than atrial fibrillation
  * Psychiatric illness/social situations that would limit compliance with study requirements
* Refractory nausea or vomiting, swallowing disorder, or malabsorption syndrome that would interfere with swallowing or absorbing the study medication
* Pregnant and/or breast-feeding women
* Previous or concurrent malignancy, except for the following circumstances:

  * Disease-free for at least three years and deemed by investigator to be at low risk for recurrence of that malignancy
  * Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin)
* History of solid organ transplantation or other condition requiring the use of immunosuppressive medications
* Uncontrolled hypertension (systolic BP \>= 150 or diastolic BP \>= 100 that cannot be controlled with medications)
* A mean left ventricular ejection fraction (LVEF) less than 45%