"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

October 28, 2020 updated by: Yuehua Huang

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

600

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Sun Yat-sen University
        • Contact:
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Nanfang Hospital
        • Contact:
      • Guangzhou, Guangdong, China, 510630
        • Recruiting
        • The Third Affiliated Hospital of Zhongshan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MSDCV immune therapy combined with radical surgery therapy
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
Drug: Cyclophosphamide
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）
Other Names:
  • Endoxan
Biological: Multiple Signals loaded Dendritic Cells Vaccine
one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, intravenous driptotal 6 times;
Other Names:
  • MSDCV
No Intervention: Radical surgery therapy
Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time
Experimental: MSDCV immune therapy combined with TACE therapy
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
Drug: Cyclophosphamide
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）
Other Names:
  • Endoxan
Biological: Multiple Signals loaded Dendritic Cells Vaccine
one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, intravenous driptotal 6 times;
Other Names:
  • MSDCV
No Intervention: TACE therapy
Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: perform when necessary according to Subjects condition
Experimental: MSDCV immune therapy combined with targeted agents therapy
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
Drug: Cyclophosphamide
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）
Other Names:
  • Endoxan
Biological: Multiple Signals loaded Dendritic Cells Vaccine
one time every 4 weeks during 0 weeks to 20 weeks, about 5*10^7 cells per time, intravenous driptotal 6 times;
Other Names:
  • MSDCV
No Intervention: Targeted agents therapy
Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free-Survival (PFS), month
Time Frame: 240 weeks
The time from randomization until first documented progression or death from any cause，whichever came first
240 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
serum AFP(alpha fetoprotein）, ng/ml
Time Frame: 240 weeks
Measured for each subjects at each visits
240 weeks
serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), μg/L
Time Frame: 240 weeks
Measured for each subjects at each visits
240 weeks
Overall Survival (OS), month
Time Frame: 240 weeks
The time from random assignment to death from any cause
240 weeks
tumor size, mm
Time Frame: 240 weeks
Utilizing Liver CT or MR examination
240 weeks
Number of participants with treatment-related adverse events
Time Frame: 240 weeks
Assessed by CTCAE v4.0
240 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yuehua Huang

Collaborators

Sun Yat-sen University
Nanfang Hospital of Southern Medical University

Investigators

  • Principal Investigator: Yuehua Huang, doctorate, Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2020

Primary Completion (Anticipated)

April 30, 2022

Study Completion (Anticipated)

April 30, 2022

Study Registration Dates

First Submitted

October 7, 2019

First Submitted That Met QC Criteria

March 19, 2020

First Posted (Actual)

March 23, 2020

Study Record Updates

Last Update Posted (Actual)

October 29, 2020

Last Update Submitted That Met QC Criteria

October 28, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019B110233002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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