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%