MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma

Inclusion Criteria: * Histologically or cytologically confirmed melanoma * Stage IV or stage III disease not potentially curable with surgery * Documented tumor progression * Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan * Must have tumor tissue (block or unstained slides) available for IHC studies * No primary uveal or mucosal melanoma * No active or untreated brain metastases * Treated brain metastases allowed provided they have been stable for ≥ 3 months * ECOG performance status 0-1 * Life expectancy \> 3 months * WBC ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST/ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment * No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption * No concurrent uncontrolled illness, including, but not limited to, any of the following: * Ongoing or active infection or bleeding * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situation that would limit compliance with study requirements * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 * Any number of prior therapies allowed * At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered * At least 4 months since prior anti-CTLA4 monoclonal antibody therapy * At least 4 weeks since other prior systemic therapy * No other concurrent investigational agents * No concurrent antiretroviral therapy for HIV-positive patients * No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E * No concurrent anticancer chemotherapy or other systemic drugs * Concurrent palliative radiotherapy allowed