PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of vesicular stomatitis virus (VSV)-interferon beta (IFN-β) (recombinant vesicular stomatitis virus expressing interferon beta) in patients with hepatocellular carcinoma (HCC) refractory or intolerant to sorafenib therapy. SECONDARY OBJECTIVES: I. To estimate the tumor response rate and overall survival. TERTIARY OBJECTIVES: I. To determine the pharmacokinetic (PK) profile of VSV-IFN-β in patients with HCC by measurement of VSV-IFN-β in blood by reverse transcriptase polymerase chain reaction (RT-PCR). II. To characterize the pharmacodynamics (PD) of VSV-IFN-β by way of measuring serum interferon-β and also VSV-RT-PCR of VSV-IFN-β listed above. III. Assess CD8+ T cell (both general and VSV-hIFN-β specific) and natural killer (NK) cell responses. IV. Assess status of human interferon beta pathway pre/post therapy in tumor/normal liver tissue (status of IFN-β, interferon stimulated gene factor 3 [ISGF3 complex constituting signal transducer and activator of transcription (STAT)1/2 and p48 (ISGF3 γ)]). V. Assess phosphorylation of STAT1/2 post-therapy. VI. Evaluate transcription of interferon mediated genes (protein kinase R, the death receptor-tumor necrosis factor [TNF]-related apoptosis-inducing ligand [TRAIL], 2'-5' oligoadenylate/ribonucleic acid [RNA]se L proteins, heat shock proteins [Hsp 60/70/90], major histocompatibility class antigens and interferon regulatory factor [IRF]-7). VII. Assess presence of VSV in tumor/normal liver subsequent to administration of VSV-human IFN-β (hIFN- β). OUTLINE: This is a dose-escalation study. Patients receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally on day 1. After completion of study treatment, patients are followed up every 4 weeks for up to 3 years.
Last updated: 10/04/2012