TK-based Suicide Gene Therapy for Hepatocellular Carcinoma

NCT ID: NCT00844623

Last Updated: 2013-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31
• Study Completion Date: 2008-03-31

Brief Summary

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.

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

TK99UN

escalated dosis from 2x10e10 to 2x10e12 viral particles injected intratumorally

Intervention Type: GENETIC

Other Intervention Names

Adenoviral vector encoding for HSV-TK

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role: lead

Responsible Party

Bruno Sangro Gomez-Acebo

Main investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jesus Prieto, MD

Role: PRINCIPAL_INVESTIGATOR

Clinica Universitaria de Navarra

Bruno Sangro, MD

Role: STUDY_DIRECTOR

Clinica Universitaria de Navarra

Locations

Clinica Universitaria de Navarra

Pamplona, , Spain

Countries

Spain

References

Penuelas I, Mazzolini G, Boan JF, Sangro B, Marti-Climent J, Ruiz M, Ruiz J, Satyamurthy N, Qian C, Barrio JR, Phelps ME, Richter JA, Gambhir SS, Prieto J. Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology. 2005 Jun;128(7):1787-95. doi: 10.1053/j.gastro.2005.03.024.

Reference Type: BACKGROUND

PMID: 15940613 (View on PubMed)

Sangro B, Mazzolini G, Ruiz M, Ruiz J, Quiroga J, Herrero I, Qian C, Benito A, Larrache J, Olague C, Boan J, Penuelas I, Sadaba B, Prieto J. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene Ther. 2010 Dec;17(12):837-43. doi: 10.1038/cgt.2010.40. Epub 2010 Aug 6.

Reference Type: RESULT

PMID: 20689572 (View on PubMed)

Other Identifiers

TK99UN-HCC1

Identifier Type: -

Identifier Source: org_study_id