Clinical trial NCT00844623: TK-based Suicide Gene Therapy for Hepatocellular Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Keywords: primary liver cancer, hepatoma
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2009-02-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse Events
timeFrame: Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then
Secondary outcomes:
measure: Tumor response by WHO criteria
timeFrame: at day 63 and months 4, 6, 9 y 12
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
Study officials:
affiliation: Clinica Universitaria de Navarra
name: Jesus Prieto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica Universitaria de Navarra
name: Bruno Sangro, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.