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Viral Therapy in Treating Patient With Liver Cancer
Conditions
Adult Hepatocellular Carcinoma - Recurrent Adult Liver Carcinoma
Conditions: official terms
Carcinoma - Carcinoma, Hepatocellular
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Laboratory Biomarker Analysis
Type: Other
Name: Pharmacological Study
Type: Other
Name: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta
Type: Biological
Overall Status
Recruiting
Summary
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).
Detailed Description
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
I. To estimate the tumor response rate and overall survival.
TERTIARY OBJECTIVES:
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.
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.
SECONDARY OBJECTIVES:
I. To estimate the tumor response rate and overall survival.
TERTIARY OBJECTIVES:
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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 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
- 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
Location
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Status: Recruiting
Contact: Clinical Trials Referral Office - 855-776-0015
Start Date
August 2012
Sponsors
Mayo Clinic
Source
Mayo Clinic
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page