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"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Cyclophosphamide

Multiple Signals loaded Dendritic Cells Vaccine

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, hepatitis B, Dendritic cells vaccine, cell therapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

In accordance with AASLD guidelines for the diagnosis of hepatocellular carcinoma，histology or imaging confirmed as primary hepatocellular carcinoma
Patients with history of hepatitis B infection
Male and female adult subjects (18～70 years old)
Patients haven't received radiation therapy or chemotherapy or immunotherapy
Normal renal function
Blood routine test: Hb>=9g/dL, white cell count>=1.5*10^9/L, platelet count>=50*10^9/L
Liver function: bilirubin<=50umol/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 oHistory 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
Patients have history of other 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

Sites / Locations

Nanfang HospitalRecruiting
Sun Yat-sen University Cancer centerRecruiting
Sun Yat-sen UniversityRecruiting
The Third Affiliated Hospital of Zhongshan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Arm Label

MSDCV immune therapy combined with radical surgery therapy

Radical surgery therapy

MSDCV immune therapy combined with TACE therapy

TACE therapy

MSDCV immune therapy combined with targeted agents therapy

Targeted agents therapy

Arm Description

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, total 6 times; Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time before the first time of MSDCV immune therapy

Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, total 6 times; Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: the first time of TACE therapy must perform before the first time of MSDCV immune therapy， then perform when necessary according to subjects condition

Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: perform when necessary according to Subjects condition

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, total 6 times; Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

Outcomes

Primary Outcome Measures

Progression-Free-Survival (PFS), month

The time from randomization until first documented progression or death from any cause，whichever came first

Secondary Outcome Measures

serum AFP(alpha fetoprotein）, ng/ml

Measured for each subjects at each visits

serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), μg/L

Measured for each subjects at each visits

Overall Survival (OS), month

The time from random assignment to death from any cause

tumor size, mm

Utilizing Liver CT or MR examination

Number of participants with treatment-related adverse events

Assessed by CTCAE v4.0

Full Information

NCT ID

NCT04317248

First Posted

October 7, 2019

Last Updated

October 28, 2020

Sponsor

Yuehua Huang

Collaborators

Sun Yat-sen University, Nanfang Hospital, Southern Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04317248

Brief Title

"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

Official Title

Precision Study on "Cocktail" Therapy to Improve the Efficacy of Hepatitis B-related Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Unknown status

Study Start Date

April 1, 2020 (Actual)

Primary Completion Date

April 30, 2022 (Anticipated)

Study Completion Date

April 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Yuehua Huang

Collaborators

Sun Yat-sen University, Nanfang Hospital, Southern Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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, multiple signals loaded dendritic cells vaccine can efficiently present T cells with antigens of HCC sensitize their antitumor properties meanwhile low dose cyclophosphamide (CY) can effectively improve the microenvironment of immunity. Therefore, we put forward a new scientific therapy called "multiple signals loaded dendritic cells vaccine combined low dose of cyclophosphamide" combining with radical surgery or TACE or targeted agents for patients with hepatocellular carcinoma to prolong their survival time.

Detailed Description

Detailed Description Patients who have good compliance complying with the inclusion criteria will be enrolled into our research. The 600 patients will be randomly assigned to experimental group and control group with the ratio of 1:1, control group will receive radical surgery or TACE or targeted agent treatment solely; another group (experimental group) after enrollment will radical surgery or TACE or targeted agent treatment in the first course. Then 20ml blood is taken for multiple signals loaded dendritic cells (MSDCV) culture (cell culture takes 7 days). Low dose (250mg/m^2) CY treatment will be performed on patients two days before the MSDCV treatment. The MSDCV combined CY therapy will perform per 4 weeks, total 6 times. All patients are evaluated the safety and efficacy of treatment by monitoring their blood parameters, tumor indicators and imaging examinations at each visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma, hepatitis B, Dendritic cells vaccine, cell therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MSDCV immune therapy combined with radical surgery therapy

Arm Type

Experimental

Arm Description

Arm Title

Radical surgery therapy

Arm Type

No Intervention

Arm Description

Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time

Arm Title

MSDCV immune therapy combined with TACE therapy

Arm Type

Experimental

Arm Description

Arm Title

TACE therapy

Arm Type

No Intervention

Arm Description

Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: perform when necessary according to Subjects condition

Arm Title

MSDCV immune therapy combined with targeted agents therapy

Arm Type

Experimental

Arm Description

Arm Title

Targeted agents therapy

Arm Type

No Intervention

Arm Description

Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Endoxan

Intervention Description

Intravenous drip，250mg/m^2 per time，two days before each times of MSDCV therapy，total 6 times, in order to improve the immunosuppressive microenvironment of tumor，reduce CD4+CD25+FOXP3+regulatory T cells (Tregs）

Intervention Type

Biological

Intervention Name(s)

Multiple Signals loaded Dendritic Cells Vaccine

Other Intervention Name(s)

MSDCV

Intervention Description

one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, intravenous driptotal 6 times;

Primary Outcome Measure Information:

Title

Progression-Free-Survival (PFS), month

Description

The time from randomization until first documented progression or death from any cause，whichever came first

Time Frame

240 weeks

Secondary Outcome Measure Information:

Title

serum AFP(alpha fetoprotein）, ng/ml

Description

Measured for each subjects at each visits

Time Frame

240 weeks

Title

serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), μg/L

Description

Measured for each subjects at each visits

Time Frame

240 weeks

Title

Overall Survival (OS), month

Description

The time from random assignment to death from any cause

Time Frame

240 weeks

Title

tumor size, mm

Description

Utilizing Liver CT or MR examination

Time Frame

240 weeks

Title

Number of participants with treatment-related adverse events

Description

Assessed by CTCAE v4.0

Time Frame

240 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In accordance with AASLD guidelines for the diagnosis of hepatocellular carcinoma，histology or imaging confirmed as primary hepatocellular carcinoma Patients with history of hepatitis B infection Male and female adult subjects (18～70 years old) Patients haven't received radiation therapy or chemotherapy or immunotherapy Normal renal function Blood routine test: Hb>=9g/dL, white cell count>=1.5*10^9/L, platelet count>=50*10^9/L Liver function: bilirubin<=50umol/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 oHistory 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 Patients have history of other 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yuehua HYuang, doctorate

Phone

0086-13822232795

huangyh53@mail.sysu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Yifan Lian, doctorate

Phone

0086-13824441190

lianyf@mail3.sysu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuehua Huang, doctorate

Organizational Affiliation

Third Affiliated Hospital, Sun Yat-Sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nanfang Hospital

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Li Liu, doctorate

Phone

0086-18602062738

fimmu@gmail.com

Facility Name

Sun Yat-sen University Cancer center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ming Shi, doctorate

Phone

0086-13925006889

shiming@sysu.edu.cn

Facility Name

Sun Yat-sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiajun Zhang, doctorate

Phone

0086-13751725506

zhjiajun@mail.sysu.edu.cn

Facility Name

The Third Affiliated Hospital of Zhongshan University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510630

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yanhua Bi

Phone

0086-13829710921

821771928@qq.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

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