Clinical trial NCT04317248: "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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
hepatitis B
Dendritic cells vaccine
cell therapy
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
name: Nanfang Hospital, Southern Medical University
First posted: 2020-03-23
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free-Survival (PFS), month
timeFrame: 240 weeks
Secondary outcomes:
measure: serum AFP(alpha fetoprotein）, ng/ml
timeFrame: 240 weeks
measure: serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), μg/L
timeFrame: 240 weeks
measure: Overall Survival (OS), month
timeFrame: 240 weeks
measure: tumor size, mm
timeFrame: 240 weeks
measure: Number of participants with treatment-related adverse events
timeFrame: 240 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer center
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Zhongshan University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Yuehua Huang, doctorate
role: PRINCIPAL_INVESTIGATOR
References: