Carcinoma, HepatocellularPhase 1NCT00844623
TK-based Suicide Gene Therapy for Hepatocellular Carcinoma
A Phase 1 study testing TK99UN in people with Carcinoma, Hepatocellular, run by Clinica Universidad de Navarra, Universidad de Navarra at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- TK99UN
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2002to Mar 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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
- Being tested
- TK99UN
- Keywords
- primary liver cancer, hepatoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TK99UNGenetic
Also called Adenoviral vector encoding for HSV-TK
escalated dosis from 2x10e10 to 2x10e12 viral particles injected intratumorally
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Measured: Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then
Secondary outcomes (1)
Tumor response by WHO criteria
Measured: at day 63 and months 4, 6, 9 y 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2009 (estimated)
- Study startDec 2002
- Primary completionNov 2003
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de Navarra
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruno Sangro Gomez-Acebo, Clinica Universidad de Navarra, Universidad de Navarra
- Investigators
- Jesus Prieto, MD, Principal investigator, Clinica Universitaria de NavarraBruno Sangro, MD, Study director, Clinica Universitaria de Navarra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00844623
- Sponsor's protocol ID
- TK99UN-HCC1
- Status last verified
- Jan 2013
- First submitted
- 13 Feb 2009
- Last updated
- 16 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 15940613Sangro 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.
PubMed 20689572
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00844623
- Acronym / sponsor ID
- TK99UN-HCC1
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- primary liver cancer, hepatoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de NavarraUniversity, hospital or other
- Study start
- Dec 2002
- Primary completion
- Nov 2003 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 16 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TK99UNAlso: Adenoviral vector encoding for HSV-TKescalated dosis from 2x10e10 to 2x10e12 viral particles injected intratumorally | Genetic | – |
Primary outcome
Adverse Events
Time frame: Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then
1 secondary outcome
Tumor response by WHO criteria
Time frame: at day 63 and months 4, 6, 9 y 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2013.
- Background: PubMed 15940613Penuelas 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.
- Results publication: PubMed 20689572Sangro 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesus Prieto, MD principal investigator
Clinica Universitaria de Navarra
Bruno Sangro, MD study director
Clinica Universitaria de Navarra
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TK99UN in people with Carcinoma, Hepatocellular, run by Clinica Universidad de Navarra, Universidad de Navarra at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: Daily for the first 16 day, monthly thereafter for 6 months, 3-monthly since then). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00844623, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2013.