Vemurafenib + Fotemustine to Treat Advanced Melanoma Patients With V600BRAF Mutation Recurred While on Vemurafenib

Inclusion Criteria:

* Histologically confirmed melanoma harboring the V600 mutation
* Unresectable Stage IV melanoma
* At least 18 y of age
* Eastern Cooperative Oncology Group (ECOG) performance status of \<2
* In progression during treatment with Vemurafenib
* At least 2 weeks since the last radiotherapy treatment
* Life expectancy \>12 weeks
* Clinical laboratory values at screening defined as follow: lactate dehydrogenase (LDH) \< 2.0 x upper limit of normal (ULN), Hemoglobin \>9 g/dL, Absolute neutrophil count 1500/mm3, Platelet count \>100,000/mm3, Creatinine \<1.5 mg/dL (NOTE: If creatinine is \>1.5 mg/dL, subject is eligible if creatinine clearance \> 60 mL/min using the Cockgroft-Gault equation), Total bilirubin \<1.5 x ULN, Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) \<2.5 x ULN
* Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year
* Fertile men and women must use an effective method of contraception
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Female subjects who are pregnant or nursing
* Female subjects of childbearing potential or males not using or not willing to use two forms of effective contraception
* Any of the following within the 6 months prior to randomization: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications
* Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study
* Known hypersensitivity to Vemurafenib or another BRAF inhibitor
* History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias ≥ Grade 2 (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Version 4.0
* Corrected QT (QTc) interval ≥ 500 msec at baseline
* Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics)
* Has had surgery within 2 weeks (1 week for minor surgery, eg, procedures requiring only local anesthetics) prior to the first dose of study medication