Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma

Location:

Phoenix/Scottsdale, Ariz.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

Inclusion Criteria: - Histologically or cytologically confirmed hepatocellular carcinoma that is refractory to or intolerant of sorafenib based therapy - Absolute neutrophil count (ANC) >= 1000/mm^3 - Platelet count >= 80,000/mm^3 - Hemoglobin >= 10 g/dl - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 times upper limit of normal - Creatinine within institutional limits of normal - Total bilirubin =< 3 x upper limit of normal (ULN) - International normalized ratio (INR) =< 1.4 x ULN - Activated partial thromboplastin time (aPTT) within institutional limits of normal - Ability to provide informed written consent - Willingness to return to Mayo Clinic in Arizona for follow-up - Life expectancy >= 12 weeks - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 - Willingness to provide all biological specimens as required by the protocol - Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential only - Child Pugh Score A or B7 - The patient and their partner agree to use a barrier method of contraception during the study and 4 months following end of active treatment Exclusion Criteria: - Uncontrolled infection - Systemic anti-cancer therapy =< 4 weeks prior to registration - Known human immunodeficiency virus (HIV) infection - Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy - Pregnant or nursing women - History of bone marrow or solid organ transplantation - Patient for whom surgical resection or liver transplantation would be more appropriate - Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study

Last updated:

10/24/2014

NCT ID:

NCT01628640

IRB Number:

11-007114