Viral Therapy in Treating Patient With Liver Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01628640
First received: June 23, 2012
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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 Primary Hepatocellular Carcinoma
Recurrent Adult Primary Liver Cancer
Biological: recombinant vesicular stomatitis virus expressing interferon beta
Other: pharmacological study
Other: laboratory biomarker analysis
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:
  • 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: Up to 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.

  • 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.

  • 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.

  • 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: September 2014 (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.
Biological: recombinant vesicular stomatitis virus expressing interferon beta
Given intratumorally
Other Name: recombinant VSV-IFN-beta
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

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

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
  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 ClinicalTrials.gov identifier: NCT01628640

Contacts
Contact: Mitesh Borad, MD 4803018335 borad.mitesh@mayo.edu
Contact: Charanjit Singh singh.charanjit@mayo.edu

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Mitesh J. Borad, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Mitesh Borad, M.D. Mayo Clinic
Principal Investigator: Richard G. Vile, Ph.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01628640     History of Changes
Other Study ID Numbers: MC1148, NCI-2012-00890
Study First Received: June 23, 2012
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
virotherapy
oncolytic virus
vesicular stomatitis virus
interferon beta
tumor necrosis factor
protein kinase R
signal transducer and activator of transcription
natural killer cell
heat shock proteins
interferon regulatory factor
major histocompatibility class antigens
TNF-related apoptosis-inducing ligand
CD8+ T cell
Hepatocellular Carcinoma

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Stomatitis
Vesicular Stomatitis
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Mouth Diseases
Stomatognathic Diseases
Rhabdoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Adenocarcinoma
Interferon-beta
Interferons
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 20, 2014