TK-based Suicide Gene Therapy for Hepatocellular Carcinoma

January 15, 2013 updated by: Bruno Sangro Gomez-Acebo, Clinica Universidad de Navarra, Universidad de Navarra

Phase I Clinical Trial Of Gene Therapy For Hepatocellular Carcinoma By Intratumoral Injection Of TK99UN (An Adenoviral Vector Containing The Thymidine Kinase Of Herpes Simplex Virus)

The purpose of this study is to determine whether activation of a prodrug after intratumoral gene transfer is safe in humans, and to determine dose levels for further clinical development.

Study Overview

Status

Completed

Conditions

Carcinoma, Hepatocellular

Intervention / Treatment

Genetic: TK99UN

Detailed Description

The study is a phase I clinical trial evaluating the intratumoral injection of defective adenovirus containing HSVtk (the thymidine kinase of herpes simplex virus), in patients with advanced hepatocellular carcinoma that were not amenable to curative therapy. The study was conducted in a single center in Spain. Five consecutive cohorts of two patients received increasing doses of the vector by intratumoral injection and equal doses of either intravenous ganciclovir or oral valganciclovir. The dose received by each consecutive cohort of patients was progressively higher according to a prefixed scale.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Spain
- - Pamplona, Spain, 31008
    - Clinica Universitaria de Navarra

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Unequivocal diagnosis of hepatocellular carcinoma according to histological confirmation or EASL-AASLD criteria
Contraindication for surgical treatment of the disease
Detectable disease by imaging
Ability to give informed consent and to express the willingness to fulfill protocol requirements during the study

Exclusion Criteria:

Current pregnancy or breast-feeding
Acute infection
Positive anti-HIV antibodies
Hematologic alterations not attributable to hypersplenism, or in any case, intense neutropenia and thrombocytopenia, defined as neutrophil count lower than 0,5/pL or platelet count lower than 20/pL
Participation in other clinical trial during the previous month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse Events Time Frame: Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then	Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor response by WHO criteria Time Frame: at day 63 and months 4, 6, 9 y 12	at day 63 and months 4, 6, 9 y 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinica Universidad de Navarra, Universidad de Navarra

Investigators

Principal Investigator: Jesus Prieto, MD, Clinica Universitaria de Navarra
Study Director: Bruno Sangro, MD, Clinica Universitaria de Navarra

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (Actual)

November 1, 2003

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

February 13, 2009

First Submitted That Met QC Criteria