A Basic-clinical Translational Research in Hepatitis B Virus (HBV)-Specific Antigen Peptides and HepG2 Cell Lysate Co-activated Dendritic Cells Combined With Transarterial Chemoembolization (TACE) in HBV-related HCC Treatment (BTRHBVAPHCLCDCCTCHBVHCCT)

Sponsor

Yuehua Huang (Other)

Overall Status

Completed

CT.gov ID

NCT03086564

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The effect of anti-tumor treatment is not satisfying in HBV-related hepatocellular carcinoma (HBV-HCC) for reasons that HBV-HCC carries highly heterogeneous antigens to facilitate cancer cells escaping from immune surveillance and constructs an immunosuppressive microenvironment. Correspondingly, dendritic cells activated by HBV antigen peptides and HepG2 cell protein lysate can efficiently present T cells with antigens of HCC to sensitize their antitumor properties meanwhile cyclophosphamide(CY) can effectively improve the microenvironment of immunity. Therefore, we put forward a new scientific therapy called "Activated Dendritic-cells Combined Cyclophosphamide" (ADCC) combining with TACE for patients with advanced hepatocellular carcinoma to prolong their survival time.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Biological: ADCC & TACE Procedure: TACE	Phase 1/Phase 2

Detailed Description

Patients who have good compliance complying with the inclusion criteria will be enrolled into our research. The 70 patients will be randomly assigned to experimental group and control group with the ratio of 1:1, one group (control group) will go on receiving the TACE treatment solely; another group (experimental group) after enrollment will receive TACE in the first course.Then 10ml blood is taken for activated dendritic cells culture.CY treatment will be performed on patients in reasonable dose two days before the second TACE.The day when the second TACE performed, these patients will receive activated-dendritic cells simultaneously. 31 days after the first TACE therapy, all patients are determined if they should continue an additional course by monitoring their blood parameters, tumor indicators and imaging examinations. Additionally, we are setting up a treatment course containing 31 days and going to change one course into 93 days after the third course.

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Basic-clinical Translational Research in Hepatitis B Virus (HBV)-Specific Antigen Peptides and HepG2 Cell Lysate Co-activated Dendritic Cells Combined With Transarterial Chemoembolization (TACE) in HBV-related HCC Treatment

Actual Study Start Date :

May 1, 2017

Actual Primary Completion Date :

May 1, 2020

Actual Study Completion Date :

Oct 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADCC & TACE The first course : Patients in the first day of a clinical course will be performed TACE solely and keep 40ml blood sample as baseline sample for scientific research;in the 17th day, 10ml blood will be taken to culture activated dendritic cells;in 29th day, cyclophosphamide(CY) 250mg/m2 is used through an intravenous drip;in 31th day,patients are going to be performed TACE,1-2*10^8 activated dendritic cells are dripped through peripheral vein, 40ml blood sample will be taken for clinical research, simultaneously. The 31th day in the first course is the same as the first day of the second course, then we come to next therapy course. 31 days are a course of treatment, health conditions of patients who participate in will be monitored closely in the process. After previous 3-courses followed-up period, one course will be changed into 93 days.	Biological: ADCC & TACE Experimental groups will be given TACE as well as Activated-Dendritic Cells(1-2*10^8,intravenous drip),simultaneously.Cyclophosphamide(250mg/cm2,intravenous drip) will be used two days before TACE performed.
Active Comparator: TACE Every course: In the first day,patients are performed TACE solely and taken 40ml blood as baseline sample for scientific research;in the 29th day,patients are needed to reach hospital to check related indicators. In the 31th day, patients are performed TACE again. The 31th day is the same as the first day in the second course. 31 days are a course of treatment, health conditions of patients who participate in will be monitored closely in the process. After previous 3-courses followed-up period, one course will be changed into 93 days.	Procedure: TACE TACE solely in the first day of a clinical course.

Arm

Intervention/Treatment

Experimental: ADCC & TACE

The first course : Patients in the first day of a clinical course will be performed TACE solely and keep 40ml blood sample as baseline sample for scientific research;in the 17th day, 10ml blood will be taken to culture activated dendritic cells;in 29th day, cyclophosphamide(CY) 250mg/m2 is used through an intravenous drip;in 31th day,patients are going to be performed TACE,1-2*10^8 activated dendritic cells are dripped through peripheral vein, 40ml blood sample will be taken for clinical research, simultaneously. The 31th day in the first course is the same as the first day of the second course, then we come to next therapy course. 31 days are a course of treatment, health conditions of patients who participate in will be monitored closely in the process. After previous 3-courses followed-up period, one course will be changed into 93 days.

Biological: ADCC & TACE

Experimental groups will be given TACE as well as Activated-Dendritic Cells(1-2*10^8,intravenous drip),simultaneously.Cyclophosphamide(250mg/cm2,intravenous drip) will be used two days before TACE performed.

Active Comparator: TACE

Every course: In the first day,patients are performed TACE solely and taken 40ml blood as baseline sample for scientific research;in the 29th day,patients are needed to reach hospital to check related indicators. In the 31th day, patients are performed TACE again. The 31th day is the same as the first day in the second course. 31 days are a course of treatment, health conditions of patients who participate in will be monitored closely in the process. After previous 3-courses followed-up period, one course will be changed into 93 days.

Procedure: TACE

TACE solely in the first day of a clinical course.

Outcome Measures

Primary Outcome Measures

Imaging signs [4 years]
The size of tumor decrease.
Alpha-fetoprotein (AFP) [4 years]
To decrease AFP to a low level
Glypican-3 [4 years]
To decrease Glypican-3 to a low level

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:
Patients with history of hepatitis B infection
Stage B or C in Barcelona Clinic Liver Cancer(BCLC)
Eastern Cooperative Oncology Group(ECOG) scores <= 2.(without portal vein involved)
Patients have been unable to be performed surgery or liver transplant
Patients are appropriate to be performed TACE
18 or over 18 years old
Patients haven't received radiation therapy or chemotherapy or immunotherapy
Normal renal function
Blood routine test:Hb>=9g/L,white cell count>=1.510^9/L,platelet count>=5010^9
Liver function: bilirubin<=50ummol/L,aspartate aminotransferase (AST) or alanine aminotransferase (ALT)<=5 times the upper limit of normal
Child-Pugh score<=9
Human Chorionic Gonadotropin (HCG) test negative(-) if patients are women of reproductive ages
Women of reproductive ages promise to contracept until therapy course has been finished for 3 months
Patients who have signed up informed consents
Exclusion Criteria:
Extrahepatic metastasis of hepatocellular carcinoma
History of embolism, chemotherapy or radiation
History of major surgery in last 4 weeks
History of radiofrequency ablation in last 6 weeks
Acute infections in last 2 weeks
Child-Pugh scores>9
Patients with hepatic encephalopathy
Patients with ascites needed drainage
HCC with portal vein involved
Patients have history of cancer
Patients have history of HIV
Pregnant women
Patients with severe diseases like cardiac dysfunction
Patients with mental illness that influence signing informed consents
HBV infection combined with other types of hepatitis
Patients with autoimmune diseases
Immunosuppressant drugs users
Patients cannot follow our trial principle