A PHASE I STUDY TO EVALUATE THE SAFETY AND PK OF PRO-1 IN STAGE IV PATIENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study evaluates a new DNA delivery technology designed to deliver genes to sites of tumor growth, resulting in tumor-selective expression of the delivered gene. This technology, called SPLP (stable plasmid-lipid particles), allows the intravenous delivery of genes that encode therapeutic proteins. SPLP are specialized liposomes in which a single plasmid DNA is encapsulated inside a lipid bi-layer. SPLP have a long circulation lifetime in the blood. Tumor accumulation of SPLP takes place passively over the long circulation time. The fact that the blood vessels in growing tumors are leaky allows the SPLP to reach the tumor cells. This study evaluates the safety and pharmacokinetics of the intravenous delivery of Pro-1 to Stage IV metastatic melanoma subjects, followed by treatment with Valtrex. Pro-1 and Valtrex work together to kill tumor cells. The primary objectives are to evaluate the safety of escalating doses of Pro-1 and to measure the pharmacokinetics of Pro-1 clearance from the blood of treated subjects. Secondary objectives are to evaluate the presence of thymidine kinase plasmid DNA in tumor tissue in subjects with appropriate skin lesions and to evaluate the clinical side effects of Pro-1 treatment followed by Valtrex administration on treated subjects' disease.