NCT01519427

Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib

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)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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). OUTLINE: 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.

Conditions

• Recurrent Melanoma
• Stage IIIA Melanoma
• Stage IIIB Melanoma
• Stage IIIC Melanoma
• Stage IV Melanoma

Interventions

Type	Name	Description
DRUG	Akt inhibitor MK2206	Given PO
DRUG	selumetinib	Given PO
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2012-01-01
• Primary completion: 2013-05-01
• Completion: 2013-05-01
• First posted: 2012-01-27
• Last updated: 2014-06-18
• Results posted: 2014-06-18

Locations

4 sites across 1 country: United States