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