"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04317248
• Other study ID #: 2019B110233002
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2020
• Est. completion date: April 30, 2022

Study information

• Verified date: October 2020
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: Yuehua HYuang, doctorate
• Phone: 0086-13822232795
• Email: huangyh53[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatitis
• Hepatitis B
• Hepatocellular Carcinoma

Intervention

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)

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;

Locations

Country	Name	City	State
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer center	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Zhongshan University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Yuehua Huang	Nanfang Hospital of Southern Medical University, Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free-Survival (PFS), month	The time from randomization until first documented progression or death from any cause,whichever came first	240 weeks
Secondary	serum AFP(alpha fetoprotein), ng/ml	Measured for each subjects at each visits	240 weeks
Secondary	serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), µg/L	Measured for each subjects at each visits	240 weeks
Secondary	Overall Survival (OS), month	The time from random assignment to death from any cause	240 weeks
Secondary	tumor size, mm	Utilizing Liver CT or MR examination	240 weeks
Secondary	Number of participants with treatment-related adverse events	Assessed by CTCAE v4.0	240 weeks