Inclusion Criteria:

          -  AJCC (2009) stage IV melanoma, or stage III melanoma not curable by surgery and which
             is progressing or in patients whom neo-adjuvant treatment is deemed acceptable.
             Patients must have at least 1 target lesion measurable by RECIST 1.1 criteria.

          -  The melanoma must harbor an activating BRAF V600 mutation. Prior therapy with a BRAF
             and/or MEK inhibitor is allowed in the dose-escalation phase only. However, patients
             who discontinued previous RAF inhibitor due to intolerance of the drug rather than due
             to progression will not be eligible.

          -  Histologic proof of melanoma reviewed and confirmed by the treating institution. The
             melanoma must have a documented BRAFV600E or BRAFV600K mutation by genotyping or IHC12
             performed by a CLIA certified laboratory. At MSK, the Diagnostic Molecular Pathology
             laboratory has developed and implemented a targeted capture-based next-generation DNA
             sequencing assay, MSK-IMPACTTM, to profile all protein-coding exons and selected
             introns from 410 oncogenes and tumor suppressor genes in formalin-fixed paraffin
             embedded tissues (Cheng, D.T., et al., J Mol Diagn, 2015. 17(3): p. 251-64).
             MSK-IMPACTTM has been approved by the NY State Department of Health to be run as a
             clinical assay in the CLIA-compliant Diagnostic Molecular Pathology laboratory.
             MSK-IMPACTTM is capable of detecting mutations, copy number alterations, and
             structural variations. BRAF Exon15 was captured by the MSK-IMPACTTM panel and the
             c.1799T>A (p.V600E) mutation was fully validated as per NYS requirements. Detailed
             results of the validation of this mutation were included in the validation package
             submitted to NY State Department of Health.

          -  At MGH, samples will be tested using a multiplex polymerase chain reaction (PCR)
             technology called Anchored Multiplex PCR (AMP) for single nucleotide variant (SNV) and
             insertion/deletion (indel) detection in genomic DNA using next generation sequencing
             (NGS). Briefly, genomic DNA was isolated from a formalin-fixed paraffin embedded tumor
             specimen is sheared with the Covaris M220 instrument, followed by end-repair,
             adenylation, and ligation with an adapter. A sequencing library targeting hotspots and
             exons in 39 genes (including BRAF, exons 11 and 15) is generated using two hemi-nested
             PCR reactions. Illumina MiSeq 2 x 147 base paired-end sequencing results are aligned
             to the hg19 human genome reference using BWA-MEM (Li H and Durbin R. Bioinformatics
             2009;25(14):1754-60). MuTect (Cibulskis K, et al. Nat Biotechnol 2013;31(3):213-9) and
             a laboratory-developed insertion/deletion analysis algorithm are used for SNV and
             indel variant detection, respectively. This assay has been validated to detect SNV and
             indel variants at 5% allelic frequency or higher in target regions with sufficient
             read coverage. This test was developed, and its performance characteristics were
             determined by the MGH Center for Integrated Diagnostics.

          -  Patients must be adequately recovered from surgery, radiation therapy, or any surgical
             complications prior to enrollment.

          -  Age ≥ 18 years old.

          -  ECOG performance status of 0-2.

          -  The ability to swallow pills and otherwise follow the protocol.

          -  Patients with treated CNS metastases will be eligible if not symptomatic the CNS
             disease has been stable for a minium of 6 weeks and the patient requires less than or
             equal to the equivalent of 2 mg/day of dexamethasone.

          -  Patients must have adequate organ and marrow function as defined below:

               -  Absolute Neutrophil Count ≥1.5 K/mcL

               -  Platelets ≥100 K/mcL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total Bilirubin ≤ 1.2 X institutional upper limit of normal (ULN) or ≤ 3.0 X
                  institutional ULN if the patient has Gilbert's Syndrome

               -  AST (SGOT) and ALT (SGPT) ≤ 1.2 X institutional upper limit of normal (ULN)

               -  Creatinine ≤ 1.4 mg/dl

        Exclusion Criteria:

          -  Type I or Type II diabetes

          -  A history of renal failure (unless recovered for at least 6 months), lactic acidosis,
             recurrent or severe hypoglycemia, or significant chronic obstructive lung disease.
             Patients will not be excluded for reversible episodes of elevated creatinine due to
             hypovolemia.

          -  Acute or chronic liver or renal disease.

          -  Concurrent use of hypoglycemic agents or any systemic therapy for melanoma. Palliative
             limited-field radiation therapy will be allowed

          -  Current use of a prohibited medication.

          -  Vemurafenib

               -  Avoid inducers and inhibitors of CYP3A4

               -  Careful with drugs metabolized by CTP1A2 (Clozapam, olanzapine, fluvoxamine,
                  haloperidol, theophylline, caffeine).

          -  Encorafenib

               -  Avoid inducers and inhibitors of CYP3A4

               -  Avoid drugs that increase QTc interval

          -  Dabrafenib

               -  Avoid inducers and inhibitors of CYP3A4 or CYP2CA8 (Refer to Appendix C for
                  specific drugs).

          -  Presence of conditions that will interfere significantly with the absorption of drugs.

          -  A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

          -  Pregnant and/or lactating women

          -  A prior or concurrent metastatic second malignancy within 3 years, even if it does not
             require active therapy. For example, patients with concomitant indolent B-cell
             malignancies will not be eligible. Patients with a prior resected in-situ or stage I
             malignancy felt to be cured will be eligible.

          -  Other uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements. New York Heart Association class ≥2 will be an
             exclusion criterion.

          -  QTc interval > 500 msec unless a bundle branch block is also present.

          -  Patients with brain metastases unless they meet the criteria of section 6.1.8.

          -  Patients currently receiving other anti-melanoma treatment. Toxicities attributable to
             any prior therapy must have resolved to grade 1 or better prior to enrollment. Grade 2
             endocrinopathies, except diabetes, that are ongoing from prior immunotherapy will not
             exclude the patient as long as the patient is on appropriate replacement doses of
             hormone.

          -  Patients receiving steroid treatment exceeding replacement dosing

          -  In the dose expansion phase of the trial, prior treatment with a BRAF inhibitor will
             be an exclusion criterion. This includes prior adjuvant dabrafenib/trametinib.

        Inclusion of Women and Minorities:

          -  Both men and women, and members of all races and ethnic groups are eligible for this
             trial.