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