Primary Outcome Measures
Incidence of adverse events (Phase Ib and II) [Time Frame: Up to 42 days] [Designated as safety issue: ]
Response rate (partial response [PR] + complete response [CR]) (Phase II) [Time Frame: Up to 30 days] [Designated as safety issue: ]
Progression-free survival (Phase II) [Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days] [Designated as safety issue: ]
Secondary Outcome Measures
Pharmacokinetic parameters (observed plasma drug concentration, area under the curve, half-life) for trametinib and navitoclax when administered in combination (Phase Ib) [Time Frame: Days 7, 8, 21, and 22 (or days 7, 8, 14, and 15) of cycle 1, and day 1 of cycles 2, 4, 8, and 12] [Designated as safety issue: ]
Pharmacokinetic parameters (observed plasma drug concentration, area under the curve, half-life) for trametinib and navitoclax when administered in combination (Phase II) [Time Frame: Day 1 of courses 2, 4, 8, and 12] [Designated as safety issue: ]
Response rate (partial response + complete response) (Phase Ib) [Time Frame: Up to 30 days] [Designated as safety issue: ]
Percent change in levels of proteins/messenger ribonucleic acids implicated in mitogen-activated protein kinase signaling (Phase Ib and II) [Time Frame: Baseline to up to 30 days] [Designated as safety issue: ]
Percent change in levels of proteins/messenger ribonucleic acid (mRNA)s implicated in MAPK or B-cell lymphoma 2 family signaling (Phase Ib and II) [Time Frame: Baseline to up to 30 days] [Designated as safety issue: ]
Percent change in levels of proliferation markers (Ki67) (Phase Ib and II) [Time Frame: Baseline to up to 30 days] [Designated as safety issue: ]
Percent change in levels of apoptosis markers (cleaved caspase-3) (Phase Ib and II) [Time Frame: Baseline to up to 30 days] [Designated as safety issue: ]