A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Treatment With 2 mg Intralesional Allovectin-7^® Compared to Dacarbazine (DTIC) or Temozolomide (TMZ) in Subjects With Recurrent Metastatic Melanoma

Allovectin-7 is a form of gene therapy that consists of a single plasmid DNA encoding two antigens (the HLA-B7 heavy chain and beta 2-microglobulin). The plasmid is complexed in a cationic lipid delivery system to facilitate transfection of cells in solid tumors. Allovectin-7 is injected directly into the tumor. This intratumoral injection is intended to generate immune responses leading to a local and systemic response against injected and well as un-injected tumors and residual metastatic disease.

The primary end-point of the study is to compare the overall response rate at ≥24 weeks after randomization in the Allovectin-7^® arm versus the control (DTIC/TMZ) arm. Secondary endpoints are to investigate the safety/tolerability of Allovectin-7^® in comparison to DTIC/TMZ and to investigate the effect of Allovectin-7^® in comparison to DTIC-TMZ on overall survival.

Inclusion Criteria (conditions the patient must meet)

1. Confirmed Stage 3 or Stage 4 melanoma that may have had previous treatment via surgery, radiation or biologic drugs (typically Interferon Alpha or Interleukin-2)
2. At least 1 melanoma tumor that is 1cm x 1cm or greater in size (about the size of a dime) and can be injected
3. Normal blood chemistries and blood cell counts
4. At least 18 years old and able and willing to provide informed consent to participate

Exclusion Criteria
Patients who exhibit any of the following conditions at screening will not be eligible for admission into the study:

1. Previous chemotherapy treatment for melanoma
2. Melanoma lesions in the brain or liver (however, lesions in the lungs are allowed)
3. If surgical removal of all lesions would be possible and could be curative
4. Any melanoma tumors greater than 10cm x 10cm in size
5. Known condition resulting in a suppressed immune system
6. Female subjects who are pregnant

Treatment Regimen
Eligible patients will have a 66% chance of receiving Allovectin-7^® alone vs. a 33% chance of receiving standard chemotherapy (either dacarbazine or temozolomide). The treatment course recommended for patients who receive Allovectin-7^® is a minimum of 16 weeks. Each cycle will consist of weekly injections of Allovectin-7^® alone for six weeks followed by two weeks of observation and assessments. For patients who receive the chemotherapy alone, their treatment course will follow standard dosing. During the trial all patients’ tumors will be closely monitored. Patients whose melanoma does not clinically progress will be encouraged to continue on the treatment and be assessed for up to two years.