TK-based Suicide Gene Therapy for Hepatocellular Carcinoma

Carcinoma, Hepatocellular Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844623
• Other study ID #: TK99UN-HCC1
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2009
• Last updated: January 15, 2013
• Start date: December 2002
• Est. completion date: March 2008

Study information

• Verified date: January 2013
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2008
• Est. primary completion date: November 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Genetic:
• TK99UN
escalated dosis from 2x10e10 to 2x10e12 viral particles injected intratumorally

Locations

Country	Name	City	State
Spain	Clinica Universitaria de Navarra	Pamplona

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Peñuelas I, Mazzolini G, Boán JF, Sangro B, Martí-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. — View Citation

Sangro B, Mazzolini G, Ruiz M, Ruiz J, Quiroga J, Herrero I, Qian C, Benito A, Larrache J, Olagüe C, Boan J, Peñuelas I, Sádaba B, Prieto J. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events		Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then	Yes
Secondary	Tumor response by WHO criteria		at day 63 and months 4, 6, 9 y 12	No