Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.

Inclusion Criteria: * Patients with histologically proven melanoma with either c-KIT mutation or C-KIT amplification (without BRAF or NRAS mutation) * Unresectable primary or stage III or stage IV melanoma * Measurable disease (RECIST) * The inclusion of patients with primary tumor or metastasis accessible to sequential biopsies will be favored. If such lesions are present, biopsies are mandatory and not optional * No more than 1 previous specific therapy excluding tyrosine kinase inhibitors. 4 weeks wash out will be needed after cytotoxic therapy , 12 weeks wash out after anti -CTLA4 therapy or any immunological treatment * No radiotherapy within 4 weeks ; previously irradiated lesion will not be considered as measurable unless progression at inclusion * ECOG performance status \< 2 * WBC ≥ 3,000/mm³ * PNN ≥ 1,500/mm³ (G-CSF allowed) * platelets ≥ 100,000/mm³ * Hb ≥ 9.0 g/dL ( transfusions allowed as well as recombinant erythropoetin) * Creatinin clearance \> 40ml/mn * Normal kalemia * Normal magnesemia * Total bilirubin \<1.5N ; ASAT and ALAT \<2.5N * PT/INR and PTT normal * NYHA class \< 3 * Signed Written Informed Consent * Affiliated to the National Health Insurance Exclusion Criteria: * Patients refusal * Age \< 18 years * Fertile women who do not want or cannot use effective contraception during the study and up to 8 weeks after the end of study * Women pregnant or nursing * Women with positive pregnancy test at inclusion or before treatment initiation * Fertile and sexually active men whose partner are fertile women who do not use effective contraception * Clinical and/or radiographic evidence of active cerebral metastases * Severe evolutive infection * Known HIV infection * Concomitant therapy with any other anti-cancer, immunomodulator or immunosuppressing agent or radiotherapy (except palliative care if bone metastases, after acceptance of principal investigator). * Previous use of tyrosine kinase inhibitors * More than one line of prior systemic therapies of melanoma by anti-cancer agent or immunotherapy. * Received experimental treatment within 4 weeks of inclusion * Pace-maker * Cardiac dysfunction, as evaluated by one of: * Ejection fraction \< 45% (less than 28 days from inclusion) * Congenital prolonged QT * QTc \> 450 ms * Ventricular tachyarrhythmia within the past 6 months * Bradycardia at rest \< 50/mn * Major conduction dysfunction * Myocardial infarction within the previous 6 months * Unstable angina * Uncontrolled hypertension * Digestive disease that may inhibited NILITINIB absorption * Concomitant medication that may increase QT * Taking CYP3A4 inhibitors * Eating Sevilla oranges (or Sevilla oranges derivates), grapefruit (or grapefruit juice), grapes (or grapes juice), pomegranate (or pomegranate juice) * Hereditary galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.