Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer

The p53 is a vital human tumor suppressor gene. Loss of p53 suppressor function is present in the majority of human cancers. The p53 protein has a diverse range of functions including regulation of cell cycle checkpoints, cell death (apoptosis), senescence, DNA repair, maintenance of genomic integrity, and control of angiogenesis. Abnormalities of the p53 gene may impact the efficacy of standard anticancer treatments such as radiation and chemotherapy. P53 mutation and pathway dysfunction are associated with poor clinical outcomes and the presence of the p53 mutation correlates with resistance to chemotherapy and radiation. The development of somatic gene therapy has created the potential to restore wild type function of p53. SGT-53 is a complex of cationic liposome encapsulating a normal human wild type p53 DNA sequence in a plasmid backbone. This complex has been shown to efficiently and specifically deliver the p53 cDNA to the tumor cells. Introduction of the p53 cDNA sequence is expected to restore wtp53 function in the apoptotic pathway. P53 restoration has been shown most effective in enhancing cytotoxicity in combination with an agent which results in DNA damage or initiates apoptosis. This is a Phase II clinical trial of SGT-53 plus the recently approved chemotherapeutic combination of gemcitabine/Abraxane® (nab-paclitaxel) in patients with confirmed metastatic pancreatic cancer. In addition to determining Progression Free Survival at 5.5 months (PFS5.5mos), this trial will evaluate the response rate, overall survival and time to progression as well as the tolerability and safety of SGT-53 in combination with gemcitabine/nab-paclitaxel.