Hepatocellular CarcinomaPhase 2NCT04011033
Study of Adoptive Transfer of iNKT Cells Combined With TAE/TACE to Treat Unresectable HCC
A Phase 2 study testing iNKT cells, Human recombinated Interleukin-2 and TAE/TACE in people with Hepatocellular Carcinoma, run by Beijing YouAn Hospital at 1 site in China.
Trial summary
Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- iNKT cells, Human recombinated Interleukin-2 and TAE/TACE
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2018to 1 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age 18-80 years.
- Patients with hepatocellular carcinoma (BCLC, stageB/C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time.
- Life expectancy of ≥ 12 weeks.
- WBC>3.0×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.
- iNKT>10 cell/mL in peripheral blood mononuclear cell (PBMC).
- Able to understand and sign the informed consent.
Who cannot join
- Any uncontrolled systematic disease: hypertension, heart disease, and et al.;
- Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;
- Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;
- Unstable immune systematic diseases or infectious diseases;
- Combined with AIDS or syphilis;
- Patients with history of stem cell or organ transplantation;
Show all 10Show fewer
- Patients with allergic history to related drugs and immunotherapy;
- Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage;
- Pregnant or lactating subjects;
- Unsuitable subjects considered by clinicians.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Youan Hospital,Capital Medical University
Beijing, Beijing Municipality, 100069
About this study
Official title: Study of Adoptive Transfer of Invariant Natural Killer T Cells Combined With TAE/TACE to Treat Unresectable Hepatocellular Carcinoma (HCC): Phase II Clinical Trial
Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. invariant Natural Killer T (iNKT) cell exhibit antitumor activity against malignant tumors through producing high levels of cytokines. iNKT cells are abundant in the liver, but their function is defective in liver cancer. After expansion and restored function in vitro, iNKT cells can home to liver, then they play key antitumor function. We have finished a phase I study of adoptive transfer of autologous iNKT cells for treating patients with unresectable HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study was to verify the effectiveness of iNKT cell infusion in patients with unresectable HCC who had previously failed transcatheter arterial embolization (TAE) / transcatheter arterial chemoembolization (TACE).
Read the detailed description
Patients with unresectable HCC will be enrolled and divided into two groups. Patients in trial group will be treated with combination of TAE/TACE and adoptive transfer of autologus iNKT cells. TAE/TACE will be performed at 0th and 4th week. iNKT cells will be infused at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. Patients in control group will be treated with TAE/TACE at 0th and 4th week. Overall survival (OS) time, progression-free survival (PFS) time, objective response rate(ORR), disease control rate(DCR) will be monitored.
According to JSH guidelines, TAE/TACE failure is defined as an insufficient response after ≧2 consecutive TAE/TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, these patients do not respond sufficiently to TAE/TACE.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- iNKT cells, Human recombinated Interleukin-2, TAE/TACE
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iNKT cellsBiological
Also called invariant Natural Killer T cells
5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy.
Human recombinated Interleukin-2Drug
Also called IL-2
IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion.
TAE/TACEProcedure or surgery
Also called Transcatheter Arterial embolization/Transcatheter Arterial chemoembolization
TAE/TACE will be conducted to all patients at 0th week and 4th week.
| Study group | Role | What they receive |
|---|---|---|
| TAE/TACE+iNKT for unresectable HCC | Experimental | TAE/TACE combined with autologous iNKT cells infusion will be applied for patients in experimental group. TAE/TACE will be performed at 0th and 4th week. 5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. Receives: Biological: iNKT cells; Drug: Human recombinated Interleukin-2; Procedure: TAE/TACE |
| TAE/TACE for unresectable HCC | Other | TAE/TACE will be conducted at 0th week and 4th week. Receives: Procedure: TAE/TACE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival(PFS)
PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression.
Progression is defined using Modified RECIST (mRECIST),as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.
Measured: From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.
Secondary outcomes (5)
Overall Survival(OS)
OS is the duration from the date of enrollment to the date of death due to any causes.
Measured: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.
Objective Response Rate(ORR)
ORR is the proportion of patients who had a response rate including complete remission (CR) and partial remission (PR) evaluated by imaging according to mRECIST for target lesions and assessed by MRI/CT: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions；Partial Response (PR), At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Overall Response (OR) = CR + PR.
Measured: Evaluation was performed at the 12th week after the start of the treatment.
Disease Control Rate (DCR)
DCR is the proportion of patients who had a response rate including complete remission (CR), partial remission (PR) and disease stabilization (SD) evaluated by imaging according to mRECIST for target lesions and assessed by MRI/CT: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target lesions；Partial Response (PR), At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions;Stable disease(SD), Any cases that do not qualify for either partial response or progressive disease. Disease Control Rate (DCR) = CR + PR + SD.
Measured: Evaluation was performed at the 12th week after the start of the treatment.
Adverse Events(AEs)
The severities of AEs will be divided into 5 levels according to the National Cancer Institute (NCI) Common Terminology Standard for Adverse Events (CTCAE) version 4.03.
Measured: The occurrence of AEs was observed for an average of 24 weeks after the completion of treatment (between 0-11 weeks of treatment) for up to a 60 week period in total.
Time to Quality of Life (QoL) Deterioration
EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30.
The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=[1-(RS-1)/n] x100 (function) or SS=[（RS-1）/n]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level.
Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.
Measured: Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study start1 Mar 2018
- Primary completion1 Mar 2020
- Study completion1 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing YouAn Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Shijitan Hospital, Capital Medical University, Beijing Ditan Hospital
- Responsible party
- Principal investigator, LU JUN, Beijing YouAn Hospital
- Investigators
- Jun Lu, Director, Study chair, Beijing YouAn Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04011033
- Sponsor's protocol ID
- Beijing Youan Ethics [2018]016
- Status last verified
- Sep 2024
- First submitted
- 3 Jul 2019
- Last updated
- 8 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guo J, Bao X, Liu F, Guo J, Wu Y, Xiong F, Lu J. Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial. J Hepatocell Carcinoma. 2023 Aug 21;10:1379-1388. doi: 10.2147/JHC.S416933. eCollection 2023.
PubMed 37637501
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Adoptive Transfer of Invariant Natural Killer T Cells Combined With TAE/TACE to Treat Unresectable Hepatocellular Carcinoma (HCC): Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT04011033
- Acronym / sponsor ID
- Beijing Youan Ethics [2018]016
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Beijing YouAn HospitalUniversity, hospital or other
- Collaborators
- Beijing Shijitan Hospital, Capital Medical University, Beijing Ditan Hospital
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 1 Oct 2023 (actual)
- First posted
- 8 Jul 2019 (actual)
- Results
- Posted 8 Oct 2024
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) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. invariant Natural Killer T (iNKT) cell exhibit antitumor activity against malignant tumors through producing high levels of cytokines. iNKT cells are abundant in the liver, but their function is defective in liver cancer. After expansion and restored function in vitro, iNKT cells can home to liver, then they play key antitumor function. We have finished a phase I study of adoptive transfer of autologous iNKT cells for treating patients with unresectable HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study was to verify the effectiveness of iNKT cell infusion in patients with unresectable HCC who had previously failed transcatheter arterial embolization (TAE) / transcatheter arterial chemoembolization (TACE).
Detailed description
Patients with unresectable HCC will be enrolled and divided into two groups. Patients in trial group will be treated with combination of TAE/TACE and adoptive transfer of autologus iNKT cells. TAE/TACE will be performed at 0th and 4th week. iNKT cells will be infused at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. Patients in control group will be treated with TAE/TACE at 0th and 4th week. Overall survival (OS) time, progression-free survival (PFS) time, objective response rate(ORR), disease control rate(DCR) will be monitored.
According to JSH guidelines, TAE/TACE failure is defined as an insufficient response after ≧2 consecutive TAE/TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, these patients do not respond sufficiently to TAE/TACE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAE/TACE+iNKT for unresectable HCC | Experimental | Biological: iNKT cells, Drug: Human recombinated Interleukin-2, Procedure: TAE/TACETAE/TACE combined with autologous iNKT cells infusion will be applied for patients in experimental group. TAE/TACE will be performed at 0th and 4th week. 5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. |
| TAE/TACE for unresectable HCC | Other | Procedure: TAE/TACETAE/TACE will be conducted at 0th week and 4th week. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-80 years.
- Patients with hepatocellular carcinoma (BCLC, stageB/C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time.
- Life expectancy of ≥ 12 weeks.
- WBC>3.0×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.
- iNKT>10 cell/mL in peripheral blood mononuclear cell (PBMC).
Key exclusion criteria (10 listed)
- Any uncontrolled systematic disease: hypertension, heart disease, and et al.;
- Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;
- Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;
- Unstable immune systematic diseases or infectious diseases;
- Combined with AIDS or syphilis;
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 |
|---|---|---|
| iNKT cellsAlso: invariant Natural Killer T cells5×10^8-10^9/m2 iNKT cells will be infused to patients at 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. | Biological | TAE/TACE+iNKT for unresectable HCC |
| Human recombinated Interleukin-2Also: IL-2IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion. | Drug | TAE/TACE+iNKT for unresectable HCC |
| TAE/TACEAlso: Transcatheter Arterial embolization/Transcatheter Arterial chemoembolizationTAE/TACE will be conducted to all patients at 0th week and 4th week. | Procedure or surgery | TAE/TACE for unresectable HCC, TAE/TACE+iNKT for unresectable HCC |
Primary outcome
Progression-Free Survival(PFS)
Time frame: From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.
PFS is the duration from the date of enrolled into clinical trial to the date of first documentation of tumor progression. Progression is defined using Modified RECIST (mRECIST),as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.
5 secondary outcomes
Overall Survival(OS)
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months.
Objective Response Rate(ORR)
Time frame: Evaluation was performed at the 12th week after the start of the treatment.
Disease Control Rate (DCR)
Time frame: Evaluation was performed at the 12th week after the start of the treatment.
Adverse Events(AEs)
Time frame: The occurrence of AEs was observed for an average of 24 weeks after the completion of treatment (between 0-11 weeks of treatment) for up to a 60 week period in total.
Time to Quality of Life (QoL) Deterioration
Time frame: Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37637501Guo J, Bao X, Liu F, Guo J, Wu Y, Xiong F, Lu J. Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial. J Hepatocell Carcinoma. 2023 Aug 21;10:1379-1388. doi: 10.2147/JHC.S416933. eCollection 2023.
- Individual participant dataSharing planned: No
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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.
Jun Lu, Director study chair
Beijing YouAn Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing iNKT cells, Human recombinated Interleukin-2 and TAE/TACE in people with Hepatocellular Carcinoma, run by Beijing YouAn Hospital 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 6 inclusion and 10 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 8 Oct 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-Free Survival(PFS) (time frame: From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years.). 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 NCT04011033, which also lists 1 linked publication.
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 8 Oct 2024.