Clinical Trial Detail

Design: Single-arm, open-label, multicenter Phase II interventional trial

Sample size: 25 evaluable subjects

Sample accrual: 10 per year

Population: Patients with AJCC stage IIIB, IIIC or IV M1a melanoma with cutaneous or in transit lesions accessible to electroporation

Regimen: One 8-day cycle of IL-12 plasmid, 0.5 mg/ml X 1ml intratumorally, with electroporation on days 1, 5, and 8. If there is evidence of persistent disease after 180 days (6 months) and no evidence of systemic progression, patients may be retreated every 3 months at the investigator's discretion. Otherwise, only 1 cycle of treatment will be given.

Objectives: Primary:

- To determine the 24-week distant response rate (complete and partial) of patients with advanced cutaneous melanoma treated with IL-12 plasmid electroporation

Secondary:

- Local response rate

- Progression free survival

- Overall survival

- Duration of distant response

- Time to objective response

- Safety of intratumoral IL-12 in vivo electroporation

Exploratory:

- To describe the immunologic effects of IL-12 plasmid electroporation:

- Induction of intratumoral IL-12 and IFN-gamma within electroporated melanoma tumors

- Proportion of tumor-infilitrating lymphocyte subsets such as regulatory (FoxP3+) T cells at baseline and post-treatment

- Proportion of circulating lymphocyte subsets such as regulatory (FoxP3+) and effector (CD25+CD69+CD4+ and CD25+CD69+CD8+) T cells at baseline and post-treatment

- Antigen-specific cellular and humoral immune responses in peripheral blood at baseline and post-treatment and whether this is associated with clinical response

Genders Eligible for Study: Both

- 1) Pathologically documented melanoma, AJCC stage IIIB, IIIC or IV M1a with cutaneous melanoma lesions accessible to electroporation. Patients with Stage IIIB or IIIC disease may have cutaneous in-transit disease or cutaneous satellitosis and patients with Stage IV M1a disease may have either of these with distant cutaneous metastatic sites.

- 2) Age > 18 years old

- 3) ECOG performance status 0-2

- 4) 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 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.

- 5) Must have a minimum of two eligible tumors and may have up to four eligible tumors treated with electroporation.

- 6) Creatinine < 2 x upper limit of normal, and serum bilirubin within institutional normal limits obtained within 4 weeks prior to registration.

- 7) Absolute neutrophil count (ANC) > 1000/mm and platelet count > 100,000 /mm within 4 weeks prior to registration.

- 8) Able to give informed consent and able to follow guidelines given in the study

Other eligibility criteria may apply.

- 2) Concurrent immunotherapy, chemotherapy, or radiation therapy

- 3) Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.

- 4) 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.

- 5) 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.

- 6) .Patients with electronic pacemakers or defibrillators are excluded from this study as the effect of electroporation on these devices is unknown.

- 7) Life expectancy of less than 6 months

Other exclusion criteria may apply.