Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread

PRIMARY OBJECTIVE: I. To compare progression-free survival with intermittent dosing and continuous dosing of dabrafenib and trametinib among patients with metastatic BRAF V600E/K mutant melanoma. SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities of the two dosing schedules. II. To compare the frequency and severity of fever \>= grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) 4.0 of the two dosing schedules. III. To compare the response rate (complete and partial response, confirmed and unconfirmed), overall survival, and survival after progression between the two dosing schedules on step 2. TRANSLATIONAL MEDICINE OBJECTIVES: I. To evaluate whether acquired molecular events leading to reactivation of the MAPK pathway are more common among patients on the continuous dosing arm than on the intermittent dosing arm using circulating tumor deoxyribonucleic acid (DNA) (ctDNA). II. To assess the prognostic association between baseline biomarkers and early molecular events with progression free survival (PFS). III. To explore the potential interaction between treatment arm and baseline biomarkers/early molecular events with PFS. IV. To bank tissue and whole blood in anticipation of future studies to evaluate molecular events associated with clinical benefit and disease progression in patients treated with continuous versus intermittent dabrafenib and trametinib. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (CONTINUOUS DOSING): Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) on days 1-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography/computed tomography (PET/CT) or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, echocardiography (ECHO) or multigated acquisition scan (MUGA) on study. ARM II (INTERMITTENT DOSING): Patients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study. After completion of study treatment, patients are followed up every 6 months for 3 years and then yearly for 2 years.