Hepatocellular CarcinomaPhase 1NCT02686372
A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation
A Phase 1 study testing TCR-T in people with Hepatocellular Carcinoma, run by Lion TCR Pte. Ltd. at 1 site in China.
Trial summary
Hepatocellular Carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- TCR-T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteChina
- Study dates
- 16 May 2018to 28 Sep 2021
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis as hepatocellular carcinoma (HCC)
- Underwent liver transplantation
- Seropositive for hepatitis B surface antigen (HBsAg), or presence of HBV DNA or HBV RNA before liver transplantation
- Expression of TCR-T target epitopes within specific human leukocyte antigen (HLA) class I profile
- No major post-operative complication
- Life expectancy of at least 3 months
- Ability to provide informed consent
- Ability to comply with study procedures
Who cannot join
- Known, clinically suspected or has history or central nervous system (CNS) and bone metastasis
- Significant ongoing immunologic rejection based on pathology and clinical diagnosis
- Evidence or history of significant bleeding diathesis or coagulopathy
- Prior exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy
- Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS)
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- Women who are pregnant or breast-feeding
- Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital, Sun-Yat Sen University
Guangzhou, Guangdong, 510080
About this study
Official title: A Phase I Study of T Cell Receptor-Redirected T Cell Infusion For Prevention of Hepatocellular Carcinoma Recurrence in Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma Post Liver Transplantation
Hepatocellular Carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.
Read the detailed description
A open-label, cohort clinical study of T cell receptor-redirected T cells to prevent recurrence of HBV-related hepatocellular carcinoma after liver transplantation. Subjects will be enrolled into the observation cohort or treatment cohort.
Subjects enrolled in the treatment group will receive escalating doses of HBV/ TCR expressing autologous T cells after confirming eligibility. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse.
Upon disease recurrence, eligible patient may receive HBV specific T-cell receptor (TCR-T) treatment.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- TCR-T, No intervention and TCR-T (at crossover)
- Keywords
- hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCR-TBiological
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
No intervention and TCR-T (at crossover)Biological
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
| Study group | Role | What they receive |
|---|---|---|
| HBV/TCR-T cell infusion | Experimental | Subjects enrolled in the experimental (treatment) group will receive escalating doses of HBV/ TCR expressing autologous T cells. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse. Receives: Biological: TCR-T |
| No intervention and TCR-T (at crossover) | Other | No intervention and to be crossover to experimental arm upon confirmation of disease recurrence. Receives: Biological: No intervention and TCR-T (at crossover) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate safety of the TCR-T treatment
Measures include
- assessments of Adverse Events (AEs) and Serious AEs,
Measured: Start of Treatment until 28 days post last dose
Secondary outcomes (3)
To evaluate Progression Free Survival rate
PFS
Measured: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate Duration of response rate
DOR
Measured: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate objective response rate
ORR
Measured: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study start16 May 2018
- Primary completion28 Sep 2021
- Study completion28 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lion TCR Pte. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Responsible party
- Sponsor
- Investigators
- Xiaoshun He, MD, Principal investigator, First Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02686372
- Sponsor's protocol ID
- LTCR-HCC-1-1
- Status last verified
- Jun 2022
- First submitted
- 17 Feb 2016
- Last updated
- 30 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.
PubMed 25308176Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.
PubMed 21145860Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.
PubMed 23941866
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of T Cell Receptor-Redirected T Cell Infusion For Prevention of Hepatocellular Carcinoma Recurrence in Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma Post Liver Transplantation
- ClinicalTrials.gov ID
- NCT02686372
- Acronym / sponsor ID
- LTCR-HCC-1-1
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Lion TCR Pte. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Study start
- 16 May 2018 (actual)
- Primary completion
- 28 Sep 2021 (actual)
- Study completion
- 28 Sep 2021 (actual)
- First posted
- 19 Feb 2016 (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.
Hepatocellular Carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.
Detailed description
A open-label, cohort clinical study of T cell receptor-redirected T cells to prevent recurrence of HBV-related hepatocellular carcinoma after liver transplantation. Subjects will be enrolled into the observation cohort or treatment cohort.
Subjects enrolled in the treatment group will receive escalating doses of HBV/ TCR expressing autologous T cells after confirming eligibility. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse.
Upon disease recurrence, eligible patient may receive HBV specific T-cell receptor (TCR-T) treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HBV/TCR-T cell infusion | Experimental | Biological: TCR-TSubjects enrolled in the experimental (treatment) group will receive escalating doses of HBV/ TCR expressing autologous T cells. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse. |
| No intervention and TCR-T (at crossover) | Other | Biological: No intervention and TCR-T (at crossover)No intervention and to be crossover to experimental arm upon confirmation of disease recurrence. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis as hepatocellular carcinoma (HCC)
- Underwent liver transplantation
- Seropositive for hepatitis B surface antigen (HBsAg), or presence of HBV DNA or HBV RNA before liver transplantation
- Expression of TCR-T target epitopes within specific human leukocyte antigen (HLA) class I profile
- No major post-operative complication
Key exclusion criteria (8 listed)
- Known, clinically suspected or has history or central nervous system (CNS) and bone metastasis
- Significant ongoing immunologic rejection based on pathology and clinical diagnosis
- Evidence or history of significant bleeding diathesis or coagulopathy
- Prior exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy
- Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS)
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 |
|---|---|---|
| TCR-TAutologous T cells transfected with mRNA encoding HBV antigen-specific TCR | Biological | HBV/TCR-T cell infusion |
| No intervention and TCR-T (at crossover)Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR | Biological | No intervention and TCR-T (at crossover) |
Primary outcome
To Evaluate safety of the TCR-T treatment
Time frame: Start of Treatment until 28 days post last dose
Measures include - assessments of Adverse Events (AEs) and Serious AEs,
3 secondary outcomes
To evaluate Progression Free Survival rate
Time frame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate Duration of response rate
Time frame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
To evaluate objective response rate
Time frame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
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 30 Jun 2022.
- Background: PubMed 25308176Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.
- Background: PubMed 21145860Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.
- Background: PubMed 23941866Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.
- Individual participant dataSharing planned: No
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
Xiaoshun He, MD principal investigator
First Affiliated Hospital, Sun Yat-Sen University
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 TCR-T in people with Hepatocellular Carcinoma, run by Lion TCR Pte. Ltd. at 1 site in China.
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 8 inclusion and 8 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 30 Jun 2022. 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 China. 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?
To Evaluate safety of the TCR-T treatment (time frame: Start of Treatment until 28 days post last dose). 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 NCT02686372, which also lists 3 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 30 Jun 2022.