Malignant Melanoma
Conditions
Keywords
melanoma, electroporation, IL-12, gene therapy, gene transfer
Brief summary
The purpose of this research study is to study a type of gene therapy treatment called plasmid electroporation. This type of treatment involves the injection of a gene into some melanoma tumors located near the surface of the skin, followed by a burst of electricity into the tumor to cause the tumor to take up the gene. This study is a Phase I study to determine the side effects and the correct dose of this type of treatment and also its effectiveness in treating melanoma. While the electroporation technique has been used in people, the combination of plasmid injection and electroporation is being tried in human beings for the first time.
Interventions
BIOLOGICALIL-12p DNA
Plasmid IL-12 will be administered as an intratympanic (IT) injection.
PROCEDUREIntratumoral Electroporation
The electroporation apparatus with the electrical contacts will be placed around the tumor site and activated.
Sponsors
National Gene Vector Laboratory
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants 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/mm\^3 and platelet count \> 100,000 /mm\^3 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 8 weeks | MTD of intralesionally electroporated IL-12 plasmid (pIL-12) as well as a recommended dose for Phase II study. Dose-Limiting Toxicity (DLT): will be defined as hematologic toxicities or diarrhea greater than grade 3, and nonhematologic toxicities greater than grade 2 as defined in the NCI common toxicity criteria, Version 3.0. Significant local skin breakdown, cellulitis, bleeding or ulceration will preclude treatment of particular tumor nodules although treatment of other nodules can continue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local and Systemic Response | 8 weeks | Number of participants with tumor response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Local and Systemic Expression of IL-12 and IFN Gamma | 8 weeks | Cytokine expression measured by enzyme-linked immunosorbent assay (ELISA). |
Countries
United States
Outcome results
None listed