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| Name | Class |
|---|---|
| Beijing Shijitan Hospital, Capital Medical University | OTHER |
| Beijing Ditan Hospital | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| TAE/TACE for unresectable HCC | Other | TAE/TACE will be conducted at 0th week and 4th week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| iNKT cells | Biological | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival(OS) | OS is the duration from the date of enrollment to the date of death due to any causes. | From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months. |
| Objective Response Rate(ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jun Lu, Director | Beijing YouAn Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Youan Hospital,Capital Medical University | Beijing | Beijing Municipality | 100069 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37637501 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | TAE/TACE+iNKT for Unresectable HCC | 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. iNKT cells: 5×10^8-10^9/m2 iNKT cells will be infused to patients at1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. Human recombinated Interleukin-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
| FG001 | TAE/TACE for Unresectable HCC | TAE/TACE will be conducted at 0th week and 4th week. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | TAE/TACE+iNKT for Unresectable HCC | 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 1st, 3rd, 5th, 7th, 9th, 11th week after first TAE/TACE therapy. iNKT 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-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Median | 95% Confidence Interval | months | From date of enrollment to disease progression according to mRECIST, or death from any cause, whichever occurred first，approximately 2 years. |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TAE/TACE+iNKT for Unresectable HCC | 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. iNKT 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-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Systematic Assessment |
One limitation of our study is that patients only received two cycles of TAE and the duration of iNKT therapy was only 3 months; thus, our study was not long enough to adequately assess OS. A second limitation was the small sample size, but our promising data prompts future studies in larger cohorts to more thoroughly delineate how iNKT cell therapy can be used in the context of TACE/TAE to improve therapeutic options for patients with unresectable HCC.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lu Jun | BeijingYouan Hospital | +86-010-83997153 | lujun98@ccmu.edu.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 1, 2017 | Mar 28, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D007376 | Interleukin-2 |
| ID | Term |
|---|---|
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
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| Human recombinated Interleukin-2 | Drug | IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days after iNKT cells infusion. |
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| TAE/TACE | Procedure | TAE/TACE will be conducted to all patients at 0th week and 4th week. |
|
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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. |
| 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. | 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. | 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. | Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks. |
| BG001 | TAE/TACE for Unresectable HCC | TAE/TACE will be conducted at 0th week and 4th week. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | TAE/TACE for Unresectable HCC | TAE/TACE will be conducted at 0th week and 4th week. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. |
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|
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| Secondary | Overall Survival(OS) | OS is the duration from the date of enrollment to the date of death due to any causes. | Posted | Median | 95% Confidence Interval | months | From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months. |
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| Secondary | 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. | Posted | Count of Participants | Participants | Evaluation was performed at the 12th week after the start of the treatment. |
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|
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| Secondary | 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. | Posted | Count of Participants | Participants | Evaluation was performed at the 12th week after the start of the treatment. |
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| Secondary | 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. | Posted | Count of Participants | Participants | 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. |
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| Secondary | 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. | Posted | Median | 95% Confidence Interval | months | Data will be collected at baseline and every 4 weeks until disease progression, then every 8 weeks for up to 60 weeks. |
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| 5 |
| 27 |
| 0 |
| 27 |
| 14 |
| 27 |
| EG001 | TAE/TACE for Unresectable HCC | TAE/TACE will be conducted at 0th week and 4th week. TAE/TACE: TAE/TACE will be conducted to all patients at 0th week and 4th week. | 4 | 27 | 0 | 27 | 15 | 27 |
| Fever | General disorders | Systematic Assessment |
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| Callosity | General disorders | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Alkaline phosphatase increased | Investigations | Systematic Assessment |
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| Glutamyl transpeptidase increased | Investigations | Systematic Assessment |
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| Cholesterol high | Investigations | Systematic Assessment |
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| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| Fatigue(Any Grade) |
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| Fatigue(≧ Grade 3) |
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| Fever (Any Grade) |
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| Fever (≧ Grade 3) |
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| Injection site reaction(Any Grade) |
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| Injection site reaction (≧ Grade 3) |
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| Callosity(Any Grade) |
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| Callosity(≧ Grade 3) |
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| Activation time of partial prothrombin (Any Grade) |
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| Activation time of partial prothrombin (≧ Grade 3) |
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| Alanine aminotransferase increased (Any Grade) |
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| Alanine aminotransferase increased (≧ Grade 3) |
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| Aspartate aminotransferase increased (Any Grade) |
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| Aspartate aminotransferase increased (≧ Grade 3) |
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| Blood bilirubin increased (Any Grade) |
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| Blood bilirubin increased (≧ Grade 3) |
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| Alkaline phosphatase increased (Any Grade) |
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| Alkaline phosphatase increased (≧ Grade 3) |
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| Glutamyl transpeptidase increased (Any Grade) |
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| Glutamyl transpeptidase increased (≧ Grade 3) |
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| Cholesterol high(Any Grade) |
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| Cholesterol high(≧ Grade 3) |
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