Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
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
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
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Anti-tumor response defined as either a CR, PR, or SD as defined by RECIST
The response proportion for each cohort will be reported along with a 95% confidence interval.
Up to 4 weeks
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|