Viral Therapy in Treating Patient With Liver Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Mayo Clinic
National Cancer Institute (NCI)
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Mayo Clinic Identifier:
First received: June 23, 2012
Last updated: April 19, 2016
Last verified: April 2016
The primary purpose of this study is to evaluate the safety of a viral agent called vesicular stomatitis virus for the use in patients with liver cancer. The study virus has a gene inserted into it which will allow for the production of interferon beta, which is a substance that will have the dual functions of restricting the spread of the virus to the tumor cells and not healthy liver cells and also to have some independent anti-cancer activity. Although the primary goal of this study is to evaluate the safety of delivery of this viral agent to people, patients may benefit clinically by having shrinkage or stabilization of their tumor or reduction in their cancer related symptoms (e.g. pain).

Condition Intervention Phase
Adult Hepatocellular Carcinoma
Recurrent Adult Liver Carcinoma
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Best tumor response, defined as the best objective status recorded among patients with measurable disease at baseline using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: From the start of the treatment until disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by dose level). Examined in an exploratory and hypothesis-generating fashion.

  • Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed by dose level to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Examined in an exploratory and hypothesis-generating fashion.

  • MTD, defined as the highest dose at which no more than 1/6 patients experiences dose limiting toxicities (DLT), graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    DLT defined as an adverse event during the first 4 weeks following injection. A modified "3+3" Fibonacci dose escalation scheme will be used Examined in an exploratory and hypothesis-generating fashion.

  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier (overall and by dose level). Examined in an exploratory and hypothesis-generating fashion.

Estimated Enrollment: 48
Study Start Date: August 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (viral therapy)
Patients receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally on day 1.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Given intratumorally
Other Names:
  • Recombinant VSV-IFN-beta
  • VSV-hIFN-b

Detailed Description:


I. To determine the maximum tolerated dose (MTD) of vesicular stomatitis virus (VSV)-interferon beta (IFN-beta) (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-beta in patients with HCC by measurement of VSV-IFN-beta in blood by reverse transcriptase polymerase chain reaction (RT-PCR).

II. To characterize the pharmacodynamics (PD) of VSV-IFN-beta by way of measuring serum interferon-beta and also VSV-RT-PCR of VSV-IFN-beta listed above.

III. Assess CD8+ T cell (both general and VSV-hIFN-beta 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-beta, 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-beta (hIFN- beta).

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 3 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 x ULN
  • Creatinine =< 1.5 x ULN
  • Total bilirubin =< 3 x ULN
  • International normalized ratio (INR) =< 1.5 x ULN
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01628640

United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Mitesh J. Borad         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
FDA Office of Orphan Products Development
Principal Investigator: Mitesh Borad Mayo Clinic
  More Information

Responsible Party: Mayo Clinic Identifier: NCT01628640     History of Changes
Other Study ID Numbers: MC1148  NCI-2012-00890  11-007114  MC1148  P30CA015083  Orphan Product 
Study First Received: June 23, 2012
Last Updated: April 19, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on May 26, 2016