Phase 2 Study of Intralesional PV-10 for Metastatic Melanoma

The primary objective of this study is to investigate the effectiveness of intralesional (IL) PV-10 for locoregional treatment of metastatic melanoma. This study will also include assessment of response in untreated bystander lesions following intralesional injection of PV-10 into targeted lesions. Additional objectives are to determine the safety profile of PV-10 following intralesional injection, and assess the pharmacokinetic profile of PV-10 in the bloodstream following intralesional injection.

This is a multicenter, open-label, single-agent study. Subjects with at least one melanoma lesion ≥ 0.2 cm in diameter that can be accurately measured by ruler/caliper or ultrasound will receive intralesional injection of PV-10 into each of up to twenty (20) Study Lesions. Additionally, one to two measurable Bystander Lesions may remain untreated and will be followed for assessment of bystander response.

To accurately reflect anticipated clinical use, repeat dosing of treated lesions will be allowed at the Investigator's discretion at weeks 8, 12 and 16 following initial treatment for those lesions not exhibiting complete response. Subjects will be followed for 52 weeks following initial treatment with PV-10.

Eligibility Criteria:
Inclusion Criteria:

* Men or women, age 18 years or older.
* Histologically or cytologically confirmed metastatic melanoma, AJCC (2002) Stage III (regional lymph node metastasis, in-transit metastasis or satellite metastasis) or Stage IV (distant metastasis).
* Measurable disease in at least one lesion ≥ 0.2 cm in diameter that can be accurately measured by ruler/caliper or ultrasound. Target, Non-Target and Bystander Lesions selected by discretion of Investigator.
* Performance Status: ECOG 0-2.
* Life Expectancy: At least 6 months.
* Hematopoietic:

  * White blood cell count (WBC) no less than 2500/mm3 (2.5 x 10E9/L).
  * Absolute neutrophil count (ANC) no less than 1,000/mm3 (1.0 x 10E9/L).
  * Platelet count no less than 90,000/mm3 (90 x 10E9/L).
* Blood Chemistry:

  * Creatinine no greater than 1.5 times the upper limit of normal (ULN).
  * Total bilirubin no greater than 1.5 times the upper limit of normal (ULN).
  * AST/ALT no greater than 3 times the upper limit of normal (ULN).
* Thyroid Function:

  * Total T3 or free T3 (serum triiodothyronine), total T4 or free T4 (serum thyroxine) and THS (serum thyrotropin) within normal limits.
* Cardiovascular Function:

  * No clinically significant cardiovascular disease.
* Respiratory Function:

  * No clinically significant respiratory disease.
* Immunological Function:

  * No known immunodeficiency disease. Subjects must have adequate immune system function in the opinion of the Investigator.

Exclusion Criteria:

* Radiation therapy within 4 weeks of study treatment or to any Study Lesion within 12 weeks of study treatment.
* Chemotherapy:

  * Chemotherapy or other systemic cancer therapy within 4 weeks of study treatment (6 weeks for nitrosoureas or mitomycin).
  * Regional chemotherapy (limb infusion or perfusion) within 12 weeks of study treatment.
* Local treatment (e.g., surgery, cryotherapy, radiofrequency ablation) to the treatment area within 4 weeks of study treatment.
* Investigational agents within 4 weeks (or 5 half-lives) of study treatment.
* Photosensitizing agents within 5 half-lives of study treatment.
* Anti-tumor vaccine therapy within 6 weeks of study treatment.
* Concurrent or Intercurrent Illness:

  * Severe diabetes.
  * Extremity complications due to diabetes.
  * Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise their safety or compliance or interfere with interpretation of study results.
  * Thyroid disease (subclinical or ongoing), goiter, partial thyroidectomy, previous radioiodine- or surgically-treated Graves' hyperthyroidism or cystic fibrosis, or taking thyroid hormone medication.
* Pregnancy:

  * Female subjects who are pregnant or lactating.
  * Female subjects who have positive serum ßHCG pregnancy test taken within 7 days of PV-10 treatment.
  * Fertile subjects who are not using effective contraception.