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| Name | Class |
|---|---|
| Newish Technology (Beijing) Co., Ltd. | INDUSTRY |
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The purpose of this study is to assess the efficacy and safety of combining autologous Tcm immunotherapy and TACE in HCC patients with MVI after radical resection. Patients will be assigned either to the experimental arm to receive autologous Tcm immunotherapy and TACE or to the active comparator (TACE alone).
Hepatocellular carcinoma (HCC) is one of the common cancer worldwide, which is the third cause of cancer related deaths. Radical hepatic resection remains the main treatment for hepatocellular carcinoma, the 5-year survival rate of HCC after surgery was 60-70%. Unfortunately, HCC is prone to postoperative recurrence that more than 50% of patients relapse within 2 years, which has become the key to restrict the therapeutic effect of hepatocellular carcinoma. Microvascular invasion (MVI) is one of the main risk factors for poor prognosis in HCC.
Autologous cell immunotherapy is to collect patient's own immune cells and then given back to the patient after amplified in vitro that can improve the anti-tumor immune response. Tcm (central memory T cells) are effective anti-tumor immune cells that exhibit the long-term survival and self-renewal capacity in vivo. Autologous Tcm immunotherapy combining chemotherapy, surgery or radiotherapy would effectively prolong survival period, prevent tumor recurrence and metastasis, then improve quality of life in patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TACE+Tcm group | Experimental | Experimental arm: TACE plus autologous Tcm immunotherapy to treat HCC. |
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| TACE group | Active Comparator | Active comparator: TACE to treat HCC. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TACE plus autologous Tcm immunotherapy | Combination Product | TACE:transcatheter arterial chemoembolization. Autologous Tcm immunotherapy: to collect patient's own immune cells and then given back to the patient after amplified in vitro. |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-free Survival (RFS) Time | Recurrence-free survival was defined as the interval (in months) between hepatectomy and diagnosis of recurrence using either intrahepatic recurrence or extrahepatic metastasis. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) Rate at 24 Months | Overall survival rate = the number of patients in TACE/TACE+Tcm group survived at 24 months/the number of total patients assigned into TACE/TACE+Tcm group. | 24 months |
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Inclusion Criteria:
Be willing and able to provide written informed consent for the study.
Subject has accepted radical hepatic resection, and preoperative imaging is no vascular invasion.
Postoperative pathology confirmed Hepatocellular carcinoma with negative margin and microvascular invasion (MVI).
Age between 18-75 years old.
Radiology confirmed complete response (CR) after radical surgery.
Child-Pugh A.
Eastern Cooperative Oncology Group(ECOG) body condition score 0.
Adequate hepatic and renal function:
Hemoglobin ≥ 9.0g/dl. Absolute neutrophil count (ANC) > 1,500/mm3. Platelets ≥ 50,000/ul. Total bilirubin (TBIL) ≤ 2mg/dl. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 the upper limit of normal (ULN) for the institution.
Alkaline phosphatase (ALP) ≤ 4 the upper limit of ULN. Prothrombin time (PT) > 50% or prothrombin time-international normalized ratio (PT-INR) < 2.3.
Serum creatinine (CREA) ≤ 1.5 the upper limit of ULN.
Female subjects have had a negative blood pregnancy test within 2 week,
Subjects be willing to use appropriate contraception during the trial and 2 weeks after the last administration of immunotherapy.
Radiology such as CT and MRI were performed in 4 weeks before the study.
Exclusion Criteria:
Recurrent HCC.
Portal vein embolus.
Cardiovascular disease:
Evidence of NYHA functional class III or IV heart disease. Unstable coronary artery disease (CAD) is not allowed, while Myocardial Infarction (MI) 6 months of starting study is allowed.
Cardiac arrhythmias requiring antiarrhythmic drugs except β-blockers or digoxin are not allowed.
Uncontrolled hypertension.
History of Human Immunodeficiency Virus (HIV) or syphilis infection.
Severe inflammation, NCI CTCAE Version 3.0 grade > 2.
Epilepsy requiring steroid or antiepileptic drugs.
History of allotransplantation.
History or any evidence of hemorrhage.
Subjects undergoing renal dialysis.
Pregnancy or breast-feeding.
Prior or undergoing cancers that primary sites are different from the carcinoma of this study. Exceptions to this are:
Cervical carcinoma in situ (CIS) Cured basal cell carcinoma Superficial bladder tumor Cured cancers over 3 years before the study
Uncontrolled Ascites by diuretic treatment.
History of encephalopathy.
Gastrointestinal hemorrhage in 30 days before the study.
History of esophageal variceal hemorrhage and it is no effective treatment to prevent the recurrence of hemorrhage.
Major surgery except radical hepatic resection was performed in 4 weeks before the study.
Autologous bone marrow transplantation (ABMT) in 4 weeks before the study.
Concurrent treatment on another clinical trial or treatment on another clinical trial in 4 weeks before the study.
Drug abuse, medical treatment, mental illness or social disorders that would interfere with subjects' participation, or confound the results of the trial.
Any condition that would interfere with or endanger the safety and compliance of subjects.
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| Name | Affiliation | Role |
|---|---|---|
| Hong Zhao | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Beijing | Beijing Municipality | 100021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34926296 | Derived | Cai J, Zhao J, Liu D, Xie H, Qi H, Ma J, Sun Z, Zhao H. Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study. Front Oncol. 2021 Dec 3;11:781029. doi: 10.3389/fonc.2021.781029. eCollection 2021. |
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This study was not of a randomized design, patients were recruited by their willingness to receive the Tcm transfusion as the adjuvant therapy after screening and meeting the eligibility criteria. As pathological classification with MVI was determined after 1 week postoperatively, patients consented with radical operation would be screened again.
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| ID | Title | Description |
|---|---|---|
| FG000 | TACE Group | Control arm: only TACE (TACE: transcatheter arterial chemoembolization) |
| FG001 | TACE+Tcm Group | Experimental arm: TACE plus autologous Tcm immunotherapy (TACE:transcatheter arterial chemoembolization) Autologous Tcm immunotherapy: collected patient's own immune cells and then transfused back to patient after being amplified in vitro. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Oct 31, 2019 |
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| TACE | Procedure | TACE:transcatheter arterial chemoembolization. |
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| COMPLETED |
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| NOT COMPLETED |
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Per Protocol Set (PPS):
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| ID | Title | Description |
|---|---|---|
| BG000 | TACE Group | Control arm: only TACE (TACE: transcatheter arterial chemoembolization) |
| BG001 | TACE+Tcm Group | Experimental arm: TACE plus autologous Tcm immunotherapy (TACE:transcatheter arterial chemoembolization) Autologous Tcm immunotherapy: collected patient's own immune cells and then transfused back to patient after being amplified in vitro. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Eastern Cooperative Oncology Group(ECOG) | ECOG STATUS 0, Fully active, able to carry on all pre-disease performance without restriction
| Count of Participants | Participants |
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| 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 | Recurrence-free Survival (RFS) Time | Recurrence-free survival was defined as the interval (in months) between hepatectomy and diagnosis of recurrence using either intrahepatic recurrence or extrahepatic metastasis. | PPS (Per Protocol Set) | Posted | Median | Standard Deviation | months | 12 months |
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| Secondary | Overall Survival (OS) Rate at 24 Months | Overall survival rate = the number of patients in TACE/TACE+Tcm group survived at 24 months/the number of total patients assigned into TACE/TACE+Tcm group. | Posted | Count of Participants | Participants | 24 months |
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12 months
Laboratory examination of blood tests, liver and kidney function of all patients were collected every 4 weeks during Tcm treatment and every 12 weeks after Tcm treatment in 48 weeks or ended the last follow-up. 1 patients assigned into TACE+Tcm group requested withdrawing without any administration of Tcm.
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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 | TACE Group | Control arm: only TACE (TACE: TACE:transcatheter arterial chemoembolization) | 0 | 25 | 0 | 25 | 19 | 25 |
| EG001 | TACE+Tcm Group | Experimental arm: TACE plus autologous Tcm immunotherapy (TACE:transcatheter arterial chemoembolization) Autologous Tcm immunotherapy: collected patient's own immune cells and then transfused back to patient after being amplified in vitro. | 0 | 26 | 0 | 26 | 9 | 26 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic pain | Hepatobiliary disorders | CTCAE (4.0) | Non-systematic Assessment | Patients with total bilirubin or ALT or AST elevation |
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| Bone marrow hypocellular | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | patients with decreasing white blood cells or lymphocytes |
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This study was a pilot study with small sample size, which would influence the statistical results.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Statistician of Clinical Trials | Tsinghua University | majunfan2@sina.com |
| May 11, 2020 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| Between 18 and 65 years |
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| >=65 years |
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