"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

Phase 2

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Cyclophosphamide; Biological: Multiple Signals loaded Dendritic Cells Vaccine

• Registration Number: NCT04317248
• Lead Sponsor: Yuehua Huang

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.

Study Timeline

• Study First Submitted: 2019-10-07
• Study First Submitted QC: 2020-03-19
• Study First Posted: 2020-03-23
• Study Start: 2020-04-01
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-28
• Last Update Posted: 2020-10-29
• Primary Completion: 2022-04-30
• Study Completion: 2022-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 600

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSDCV immune therapy combined with TACE therapy	Cyclophosphamide	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
MSDCV immune therapy combined with TACE therapy	Multiple Signals loaded Dendritic Cells Vaccine	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
MSDCV immune therapy combined with targeted agents therapy	Multiple Signals loaded Dendritic Cells Vaccine	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
MSDCV immune therapy combined with radical surgery therapy	Cyclophosphamide	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
MSDCV immune therapy combined with radical surgery therapy	Multiple Signals loaded Dendritic Cells Vaccine	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
MSDCV immune therapy combined with targeted agents therapy	Cyclophosphamide	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

Primary Outcome Measures

Name	Time	Method
Progression-Free-Survival (PFS), month	240 weeks	The time from randomization until first documented progression or death from any cause，whichever came first

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Sun Yat-sen University Cancer center; 🇨🇳 Guangzhou, Guangdong, China

Nanfang Hospital; 🇨🇳 Guangzhou, Guangdong, China

Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

The Third Affiliated Hospital of Zhongshan University; 🇨🇳 Guangzhou, Guangdong, China