Viral Therapy in Treating Patient With Refractory Liver Cancer or Advanced Solid Tumors

Hepatocellular Carcinoma Clinical Trial

Official title: Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma, Advanced Solid Tumors With Liver Predominant Locally Advanced/Metastatic Disease or Subcutaneous/Cutaneous Lesions

Status Active, not recruiting

Clinical Trial Summary

This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus expressing interferon beta in treating patients with liver cancer or solid tumors with lesions that have spread to other parts of the body and do not respond to treatment. The study virus has a gene inserted into it which will allow production of interferon beta, which is a substance that will restrict the spread of the virus to tumor cells and not healthy cells. It will also 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). Funding Source - FDA OOPD.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing interferon-beta (VSV-IFN-beta) in patients with hepatocellular carcinoma (HCC) refractory or intolerant to sorafenib therapy and patients with advanced solid tumors with liver predominant locally advanced/metastatic treatment refractory disease. (Arm A) II. To determine the maximum tolerated dose (MTD) of VSV-IFN-beta in patients with advanced solid tumors with subcutaneous/cutaneous lesions. (Arm B)

SECONDARY OBJECTIVES:

I. To estimate the tumor response rate, injected lesion (TNi) and distant lesion (TNd) necrosis rate (with TNi and TNd response defined as >= 30% increase in necrosis from baseline) and overall survival. (Arm A)

TERTIARY OBJECTIVES:

I. To determine the pharmacokinetic (PK) profile of VSV-IFN-beta in patients with HCC by or advanced solid tumors with liver predominant disease or subcutaneous/cutaneous lesions 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 gamma)]).

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).

VIII. For HCC patients only, assess preliminary relationships between hepatitis C genotype (in those patients that are hepatitis C positive) and any evidence of anti-tumor efficacy.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms.

ARM A: Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.

ARM B: Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 lesions on day 1.

After completion of study treatment, patients are followed up every 4 weeks for 3 years. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

• NCT number: NCT01628640
• Study type: Interventional
• Source: Mayo Clinic
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 3, 2012
• Completion date: June 15, 2025