"Cocktail" Therapy for Hepatitis B Related Hepatocellular Carcinoma

Yuehua Huang

Status and phase: Unknown; Phase 2

Conditions: Hepatocellular Carcinoma

Treatments: Biological: Multiple Signals loaded Dendritic Cells Vaccine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT04317248

2019B110233002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 6 patient groups

MSDCV immune therapy combined with radical surgery therapy

Experimental group

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

Treatment:

Drug: Cyclophosphamide

Biological: Multiple Signals loaded Dendritic Cells Vaccine

Radical surgery therapy

No Intervention group

Description:

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

MSDCV immune therapy combined with TACE therapy

Experimental group

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; 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

Treatment:

Drug: Cyclophosphamide

Biological: Multiple Signals loaded Dendritic Cells Vaccine

TACE therapy

No Intervention group

Description:

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

MSDCV immune therapy combined with targeted agents therapy

Experimental group

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

Treatment:

Drug: Cyclophosphamide

Biological: Multiple Signals loaded Dendritic Cells Vaccine

Targeted agents therapy

No Intervention group

Description:

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