MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma
Condition: Recurrent Melanoma; Stage III Skin Melanoma; Stage IV Skin Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Laboratory Biomarker Analysis; Selumetinib
Intervention description: Correlative studies; Given orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 167.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well MEK inhibitor AZD6244 works in treating patients
      with stage III or stage IV melanoma. MEK inhibitor AZD6244 may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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