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About
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.
Full description
PRIMARY OBJECTIVES:
I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244.
SECONDARY OBJECTIVES:
I. Identify other genetic predictors of sensitivity to MEK inhibition.
OUTLINE: Patients are stratified according to pAKT expression (low vs high).
Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples are collected for correlative laboratory studies. Samples are assessed for expression of pAKT, pPRAS40, and PTEN by IHC and mutations in BRAF, NRAS, KIT, and PIK3CAP by MALDI-TOF. PTEN is sequenced in tumors using whole genome amplification followed by high-throughput bidirectional dideoxynucleotide sequencing of PCR-amplified gene products.
After completion of study treatment, patients are followed for 4 weeks.
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically or cytologically confirmed melanoma
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
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:
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
Primary purpose
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167 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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