Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, hepatitis B, Dendritic cells vaccine, cell therapy
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.
Interventions
DRUGCyclophosphamide
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）
BIOLOGICALMultiple 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;
Sponsors
Sun Yat-sen University
Nanfang Hospital, Southern Medical University
Yuehua Huang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free-Survival (PFS), month | 240 weeks | The time from randomization until first documented progression or death from any cause，whichever came first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| serum AFP(alpha fetoprotein）, ng/ml | 240 weeks | Measured for each subjects at each visits |
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactYuehua HYuang, doctorate
Backup ContactYifan Lian, doctorate
Outcome results
None listed