Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma

Inclusion Criteria: * Patients must have a written informed consent. * 18 years of age. * Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification). * BRAF V600E and V600K mutated * Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. Adequate wound healing is required prior to study entry. * Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1. * Patients must have adequate hematologic, renal, and liver function: * WBC ≥ 3,000/mm3 * ANC ≥ 1500 * Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels) * Platelets ≥ 100,000/mm3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels) * Serum Creatinine ≤ 1.5 x upper limit of normal (ULN) * Serum Bilirubin ≤ 1.5 x ULN * Serum AST/ALT ≤ 2.5 x ULN * EKG documenting normal intervals. * Fully recovered from any effects of major surgery, and be free of significant detectable infection. * ECOG performance status of 0 or 1. * Free of active brain metastases by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs. * Female patients of child bearing potential must have a negative pregnancy test (within 7 days from the time of randomization). Exclusion Criteria: * Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders. This includes known HIV or AIDS-related illness, or active HBV and HCV. * Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or MEK and/or ERK inhibitors. * Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption. * Cardiac abnormalities * Mean QTc interval ≥ 480 msec at screening. * Recent ACS/AMI - defined as within 24 weeks prior to screening. * Recent PCI/PTCA - defined as within 24 weeks prior to screening. * Recent malignant cardiac arrhythmias - all except sinus arrhythmia within 24 weeks prior to screening. * Symptomatic heart failure - NYHA Class ≥ II symptoms. * Active infection or antibiotics within one-week prior to study, including unexplained fever Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial. * Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study. * Lactating females or pregnant females.