Conditions: Recurrent Melanoma Stage IIIA Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief 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.

Arms:
arm 1: Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.

Interventions: intervention 1: Akt inhibitor MK2206 intervention 2: selumetinib intervention 3: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Given PO intervention 3: Correlative studies

Protocol document: