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

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.