Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma

PRIMARY OBJECTIVES: I. To compare progression-free survival between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795. SECONDARY OBJECTIVES: I. To compare overall survival between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795. II. To compare the overall response rate between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795. III. To compare the safety and toxicity between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795. EXPLORATORY OBJECTIVES: I. To assess clinical outcomes (response rate, progression-free and overall survival) with trametinib and GSK2141795 after progression on trametinib. II. To assess toxicity with trametinib and GSK2141795 after progression on trametinib. III. To correlate clinical outcome with Gnaq/11 mutational status. IV. To assess the pharmacodynamic effects of trametinib alone and with GSK2141795, and utilize whole-transcriptome and reverse phase protein array to identify markers of sensitivity and primary resistance to trametinib alone and with GSK2141795. V. To assess for changes in circulating tumor deoxyribonucleic acid (DNA) with therapy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience objective disease progression may crossover to Arm B. (no patients will be enrolled to Arm B or Crossover therapy as of 11/6/2015) ARM B: Patients receive trametinib PO QD and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 12 weeks thereafter.