Combine TACE and Autologous Tcm Immunotherapy Versus TACE Alone for HCC With MVI After Radical Resection

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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.

Official Title
-----------------
A Single-center, Open-label, Exploratory Trial of Autologous Immunotherapy for Hepatocellular Carcinoma (HCC) With Microvascular Invasion (MVI) After Radical Resection

Conditions
-----------------
Hepatocellular Carcinoma, Malignant Neoplasm

Intervention / Treatment
-----------------
* Combination Product: TACE plus autologous Tcm immunotherapy
* Procedure: TACE


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE+Tcm group<br>Experimental arm: TACE plus autologous Tcm immunotherapy to treat HCC. | Combination Product: TACE plus autologous Tcm immunotherapy<br>* 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.<br>|
| Active Comparator: TACE group<br>Active comparator: TACE to treat HCC. | Procedure: TACE<br>* TACE:transcatheter arterial chemoembolization.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 |