Safety and Efficacy of Intramuscular Electrotransfer of Plasmid AMEP in Patients Suffering From Advanced or Metastatic Melanoma

Inclusion Criteria: * Aged over 18 years * Patient with histologically or cytologically confirmed melanoma * Patient with unresectable advanced or metastatic (stage III or IV) melanoma * Patient with progressive melanoma (any BRAF status is permitted) not responding or intolerant to previous treatments, including patients with asymptomatic and not rapidly progressive brain metastases. * Patient with a minimum of one measurable lesion according to RECIST guideline 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 * Patient having given a written informed consent Exclusion Criteria: * Patient eligible for curative treatments and/or any palliative treatments with demonstrated efficacy, including current treatments for brain metastasis, and including available BRAF inhibitors as indicated for patients carrying B-RAF mutated tumours if applicable. * Patient with history of any other cancer within five years before enrollment (except cured basal cell carcinoma or cervical cancer in situ) * Patient with inadequate organ function, defined as: * Platelet count \< 75.103 /L (\> grade 2 NCI CTCAE) * Absolute neutrophil count \< 1.109 /L (\> grade 2) * Hemoglobin \< 9 g/dL * INR increased or prolonged activated partial thromboplastin time (aPTT) upper the limit of normal (ULN) (≥ grade 1) * Creatinine clearance \< 60 mL/min (Cockcroft and Gault formula) (≥ grade 2) * Patient with ALT \> 3 ULN (≥ grade 2) or patient with symptomatic liver metastasis with ALT \> 5 ULN (\> grade 2) * Serum Total Bilirubin \> 1.5 ULN (≥ grade 2); Patient with Gilbert's syndrome could be included if hyperbilirubinemia ≤ 3 ULN * Not medically controlled coagulation disorder (i.e hemophilia, protein C or S deficiency…) * Patient with electronic pacemakers, defibrillators, or any implanted electronic device * Any cardiac dysrhythmia (\> grade 2) (i.e significant ventricular arrhythmia as persistent ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders as atrio-ventricular block 2 and 3, sino-atrial block) * Recent (less than 6 months) acute vascular diseases (i.e stroke, myocardial infarction) * Arterial vascular disorders ≥ grade 2 * Serious, non-healed wound, ulcer or bone fracture * Significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment * Evidence of ongoing or active viral or bacterial infection ( i.e bacterial infection requiring IV antibiotics) * Patient with life expectancy less than 3 months * Prior systemic therapy or any other antineoplastic treatments within the last 4 weeks, including radiotherapy or surgery * Patients who had participated in another clinical trial in the last 30 days prior to enrolment in the present clinical trial * Man and woman of child-bearing age without effective contraception method during the study and for 3 months after the last administration of Plasmid AMEP (i.e oral contraception or intra-uterine device for woman; i.e condom for man) * Pregnant or nursing women * Any significant disease, including psychiatric and neuromuscular disease, which may affect the proper evaluation of safety or efficacy or may affect ability to give informed consent * Patients unwilling or unable to comply with protocol requirements and scheduled visits * For contrast enhanced ultrasound (CEUS): known contraindications to SonoVue as described in the summary product characteristics (i.e cardiac or pulmonary history, hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue) * For the part II: prophylactic phenytoin in combination with dacarbazine.