Safety and Efficacy Study of Electrotransfer of Plasmid AMEP to Treat Advanced or Metastatic Melanoma (AMEP)

Inclusion Criteria:

1. Male or non-pregnant, non-breast feeding female;
2. Aged between 18 and 75 years;

3. Stage IIIB, stage IIIC or stage IV melanoma with:

   • At least 2 cutaneous or subcutaneous non necrotic accessible tumours;
   • Tumour size of 1 to 1.5 cm diameter;
   • No minimum distance between the 2 selected lesions;
4. Progressive melanoma not responding to previous treatments or patients refusing other therapies;
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
6. For women of child-bearing age: effective contraception method (oral contraception or intra-uterine device) used for more than 2 months before the 1st administration and to be maintained for 3 months after the last administration of Plasmid AMEP;
7. Having given a written informed consent.

Exclusion Criteria:

1. Patients who can benefit from other melanoma treatments including surgery;
2. Significant cardiac arrhythmias, electronic pacemakers, defibrillators, or any implanted electronic device;
3. Recent (less than 6 months) acute vascular diseases (stroke, MI…);
4. Advanced peripheral arterial diseases, venous ulcers, or scleroderma;
5. History or treatment of seizures within the last 5 years;
6. Clinically significant abnormality at pre-study full physical examination;
7. Any clinically significant ECG abnormalities;
8. Prior systemic therapy or any other antineoplastic treatments within the last 4 weeks, radiotherapy or surgery unrelated to the fields in question are allowed;
9. Abnormal renal function (creatinine plasma level > ULN);

10. Abnormal liver function tests (any of the following):

    • PT < 70%, ASAT, ALAT, alkaline phosphatases, GGT and/or total bilirubin > ULN in the absence of liver metastasis;
    • PT < 70%, ASAT, ALAT > 2 ULN, alkaline phosphatases > 1.5 ULN, GGT > 5 ULN and/or total bilirubin > 3 ULN in the case of liver metastases;
11. Abnormal bone marrow function: haemoglobin < 10g/dL, WBC < 3.109 /L and/or platelet count < 100.103 /L;
12. Clinically significant abnormality in pre-study laboratory tests;
13. Evidence of significant active infection (e.g., pneumonia, wound abscess, etc);
14. Intractable coagulopathy;
15. Any significant disease, including psychiatric and dermatology diseases that may affect the proper evaluation of efficacy or safety;
16. Patients who had participated in another clinical trial in the last 30 days prior to enrolment in the present clinical trial;
17. Patients unwilling or unable to comply with protocol requirements and scheduled visits.

Note: patients with brain metastases, or waiting for other therapies (i.e. isolated limb perfusion) may be included.