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.
I. To estimate the tumor response rate and overall survival.
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.
- 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
- 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: 10/04/2012
NCT ID: NCT01628640