Phase I Trial of Intratumoral pIL-12 Electroporation in Malignant Melanoma

Inclusion Criteria:

- Patients must have cytologically/histologically documented metastatic malignant
melanoma with lesions near the skin that would be accessible to electroporation and
Fine Needle Aspiration (FNA) and biopsy.

- Age > 18 years old

- Patients must have ECOG performance status 0-2

- Patients may have had prior chemotherapy or immunotherapy (with vaccines or
Interferon or IL-2) with progression or persistent disease. All chemotherapy or
immunotherapy must be stopped for 4 weeks prior to electroporation. Patients may
have had radiation therapy, but must have progressive disease after radiation therapy
if the lesions to be electroporated are within the radiation field. In addition, it
must be at least 2 weeks since administration of radiation therapy and all signs of
toxicity must have abated.

- Patients must be able to give informed consent and able to follow guidelines given in
the study

- Patients must have a minimum of two eligible tumors and may have up to four eligible
tumors treated with electroporation.

Exclusion Criteria:

- Patients may not have had prior therapy with IL-12 or prior genetic therapy

- Patients must not have evidence of significant active infection (e.g., pneumonia,
cellulitis, wound abscess, etc.) at time of study entry.

- Patients must have adequate renal and normal hepatic function (creatinine < 1.5 x
upper limit of normal (ULN), bilirubin and SGOT (AST) within institutional normal
limits) obtained within 4 weeks prior to registration.

- Patients must have absolute neutrophil count (ANC) > 1500/mm3 and platelet count >
100,000 /mm3 within 4 weeks prior to registration.

- Pregnant and breast feeding women are excluded from the study because effects on the
fetus are unknown and there may be a risk of increased fetal wastage.

- Women of childbearing age must have a negative pregnancy test and be willing to use a
highly effective method of contraception. Men who are sexually active must also be
willing to use an accepted and effective method of contraception.

- Patients with electronic pacemakers or defibrillators are excluded from this study as
the effect of electroporation on these devices is unknown. Patients with significant
cardiac arrhythmia's (including ventricular tachycardia, ventricular fibrillation or
WPW syndrome) are also excluded.

- Patients with a history of epilepsy are excluded unless they have been seizure free
over the last 5 years and are thought to be at low risk for seizure by their
neurologist.

- Tumors that invade the bone, major blood vessels or nerves are ineligible because
those tumors are contraindications to the use of electroporation.