A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma

Inclusion Criteria: * Histologically or cytologically confirmed advanced melanoma. * BRAF mutation detected by DNA sequencing of exon 15. * Age 18 or older. * ECOG Performance Status 0-2. * Appropriate tumor imaging studies (i.e. CT scan chest, abdomen and pelvis or PET/CT scan) performed within 28 days of study registration. * Patients with melanoma measurable by RECIST 1.1 criteria will be monitored using this system for evidence of disease response/progression. * Patients with a known history of brain metastases must have a diagnostic quality MRI of the brain or contrasted CT scan of the head performed within 28 days prior to registration. * Female patients of child bearing capacity must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial acitretin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue acitretin therapy. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of acitretin therapy. The second test will be need to be repeated if not performed within 14 days prior to registration. * Willingness to use at least two forms of contraception during sexual intercourse, including at least one form of barrier contraception, for at least 30 days prior to receiving the first dose of acitretin AND during the study period, AND up to 3 years after receiving the last dose of acitretin. * Patients must agree not to consume alcoholic beverages while receiving acitretin and for 2 months after cessation of therapy. * Electrocardiogram with QTc \<450 ms at baseline. * Patients must be evaluated for the following within 14 days prior to registration: * leukocytes \>3,000/mcL * absolute neutrophil count \>1,500/mcL * platelets \>100,000/mcL * Hemoglobin \>9.0 g/dL * AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal * Alkaline phosphatase \<2.5 X institutional upper limit of normal * Total bilirubin \<1.5 X institutional upper limit of normal * Renal function serum creatinine \<1.5 mg/dL OR 1.5 x institutional normal; alternatively, creatinine clearance as assessed by 24-hour urine collection ≥60 ml/min * Total cholesterol \< 239 mg/dL or \< 6.1 mmol/L * LDL \< 159 mg/d or \< 4.1mmol/L * HDL \> 40 mg/dL or \>1.0 mmol/L * Serum triglycerides \< 199 mg/dL or \< 2.2 mmol/L * Potassium 3.5-5.5 mMol/L * Magnesium 1.7-2.6mg/dL * Calcium 8.5-10.6 mg/dL Exclusion Criteria: * Known hypersensitivity to vemurafenib, acitretin, or vitamin A analogues. * Uncontrolled hypertension. * Serious and uncontrolled hypertriglyceridemia. * Uncontrolled coronary artery disease or active anginal symptoms. * Uncontrolled brain metastases. * Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or low-grade prostate cancer. * Myocardial Infarction, Transient Ischemic Attack (TIA), Cerebrovascular Accident (CVA) or symptomatic Congestive Heart Failure (CHF) within 6 months of study registration. * Corrected QTc interval \>450ms at baseline, history of congenital long QT syndrome, or known and uncorrectable electrolyte abnormalities. * History of organ or hematologic transplant. * Underlying defined genetic syndrome based on individual or family history predisposing to high risk of non-melanoma or melanoma skin cancer as assessed by the treating Oncologist. * Concurrent use of St John's Wort. * Concurrent (or within 60 days prior to acitretin dosing) use of methotrexate or other tetracyclines, phenytoin, vitamin A supplements, Tegison (etretinate) or progestin-only oral contraceptives. * Pregnant or nursing. * Receipt of any other investigational agents.