TK-based Suicide Gene Therapy for Hepatocellular Carcinoma
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)
Lead SponsorClinica Universidad de Navarra
StatusCompleted No Results Posted
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.
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.
escalated dosis from 2x10e10 to 2x10e12 viral particles injected intratumorally
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