Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib
This phase II trial studies how well selumetinib and Akt inhibitor MK2206 works in treating patients with stage III or stage IV melanoma who failed prior therapy with vemurafenib or dabrafenib. Selumetinib and Akt inhibitor MK2206 stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet know whether giving selumetinib and Akt inhibitor MK2206 together is an effective treatment for advanced melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Drug: Akt inhibitor MK2206
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of MAP Kinase Inhibition With AZD6244 Hydrogen Sulfate in Combination With MK-2206 (Akt Inhibitor) in Patients With BRAF V600-Mutant Advanced Melanoma Whose Disease Has Progressed on Prior Therapy With a Selective BRAF Inhibitor (i.e., Vemurafenib, Dabrafenib, LGX818)|
- Objective response (CR or PR) [ Time Frame: After the first 12 patients have been treated ] [ Designated as safety issue: No ]
- Analyses of biomarker expression and change to estimate effect sizes with 95% confidence intervals [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Time Frame: Time from treatment initiation to disease progression or death for any reason, up to 2 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan and Meier and compared between treatments using the logrank test.
- Overall survival [ Time Frame: Time from start of therapy to last follow-up or death for any reason, up to 2 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan and Meier and compared between treatments using the logrank test.
|Study Start Date:||January 2012|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (selumetinib and Akt inhibitor MK2206)
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Drug: Akt inhibitor MK2206
Other Name: MK2206Drug: selumetinib
Other Names:Other: laboratory biomarker analysis
I. To determine the frequency of objective clinical responses by RECIST 1.1 for these melanoma patients who have previously progressed on selective BRAF inhibitors when treated with MEK inhibitor, AZD6244 hydrogen sulfate plus Akt inhibitor, MK-2206.
II. To further characterize toxicities of both regimens in these patients who have progressed after BRAF inhibitor therapy.
I. With required fresh pretreatment biopsies on all patients, we plan to characterize the molecular state (genetic and proteomic) associated with BRAF inhibitor resistance. This may include an analysis of pathway activation, PI3/Akt or MAP kinase pathway; loss of expression of PTEN, secondary mutations in BRAF, other mutations in the MAP kinase pathway (NRAS, KRAS, HRAS, CRAF, MEK), activation of other RTKs (amplification, over expression, phosphorylation).
Patients receive selumetinib orally (PO) twice daily (BID) on days 1-21 and Akt inhibitor MK2206 PO once weekly.
After completion of study treatment, patients are followed up every 12 weeks.
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, New Jersey|
|Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Virginia|
|Virginia Commonwealth University/Massey Cancer Center|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Jeffrey Sosman||H. Lee Moffitt Cancer Center and Research Institute|