Advanced Hepatocellular Carcinoma
Conditions
Interventions
experimental group:Interventional reinfusion of CD147-CART through hepatic artery
Sponsors
Intervention and Cell Therapy Center, Peking University Shenzhen Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: (1) Aged >= 18 year and <= 70 years, both male and female; (2) Advanced hepatocellular carcinoma (HCC) patient, who is failed in at least first-line and second-line of therapy, standard systemic chemotherapy, and unwilling or intolerance to targeted therapy; Remarks: Advanced HCC is defined as not meeting the conditions of surgery / local therapy, or residual or progression after surgery / local therapy. Targeted drugs include but are not limited to sorafenib, rivarotinib, regofinib and cabotinib. (3) The main portal vein was not completely blocked, or the compensatory collateral vessels between hepatic artery and completely blocked portal vein were formed; (4) Patient with measurable HCC focus according to mRECIST; (5) Patient with histologically confirmed diagnosis of CD147+ hepatocellular carcinoma; (6) Sufficient peripheral blood can be obtained through vein from patient, and there are no other contraindications for lymphocyte collection. Peripheral blood mononuclear cells (PBMC) can be collected according to the requirements of cell preparation; (7) The child Pugh grade of liver function was grade A or B (score <= 7) before enrollment; (8) Eastern Cooperative Oncology Group(ECOG) performance score was 0-2 before enrollment; (9) Patient with a life expectancy of greater than three months; (10) After signing the informed consent, the patients can carry out diagnosis and treatment and follow-up observation according to the scheme requirements.
Exclusion criteria
Exclusion criteria: (1) Patients with fibrolamellar carcinoma of livermixed hepatocellular carcinoma or cholangiocarcinoma; (2) Patients with severe hypohepatia including jaundice, hepatic encephalopathy, refractory ascites or hepatorenal syndrome; (3) Patients with severe comorbidity, including any of the following: a. Unstable angina pectoris and/or congestive heart failure need hospitalization; b. Myocardial infarction or cerebrovascular accident (CVA) in the last 6 months; c. Chronic obstructive pulmonary disease progressions or need hospitalization; d. Severe cardiovascular, nervous system, hematological, gastrointestinal, endocrine diseases or metabolic disorders; e. Autoimmune disease or immunodeficiency disease, including such as rheumatoid arthritis, acquired immunodeficiency syndrome (AIDS), etc; f. Acute bacterial infections or fungal infections needs intravenous injection of antibiotics during cell infusion therapy; g. Tuberculosis not cured; h. Other malignancies; (4) Patients who have received gene therapy or cell therapy; (5) Patients who have received organ transplantation; (6) Patients who have received treatment of targeted drugs, immunosuppressive drugs or glucocorticoid within 2 weeks before enrollment; (7) Patients who have received chemotherapy except for lymphocyte clearance within 2 weeks before enrollment; (8) Patients who have received radiotherapy within 2 weeks before enrollment; (9) Patients who did not recover to CTCAE (v5.0) grade 1 from adverse events (excepting hair loss) of previous anti-tumor therapy before enrollment; (10) Syphilis test (TRUST) positive, Anti-HIV positive, Anti-HCV positive or HCV-RNA level higher than the lower limit of detection (LOD); (11) Patients with following abnormalities: a. Absolute neutrophil count (ANC) 1.5 x ULN (upper normal value); c. Total bilirubin (TBIL) > 2 x ULN, ALT, AST or ALP > 5 x ULN; d. Serum creatinine (Cr) >= 1.5 x ULN or glomerular filtration rate (GFR) < 60 mL/min.1.73m^2; e. Left ventricular ejection fraction (LVEF) < 50%; (12) Patients with a history of allergy or expected to be allergic to any ingredient treated in this trial; (13) Patients with known allergy to contrast medium; (14) Patients with a history of mental disorders; (15) Patients with a history of drug abuse; (16) Pregnant and lactating women; (17) Women of childbearing age and fertile men who can not take effective and adequate contraception measures (such as intrauterine device, condom, sperm killing gel, condom and uterine cap) within 3 months after receiving the research drug and post the end of the study; (18) Patients who receive any other investigational agents within the 3 months before enrollment; (19) Patients judged by investigators to be not suitable for this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety;objective response rate (ORR);duration of response (DOR);disease control rate (DCR);time to progress (TTP);progression-free survival (PFS);overall survival (OS); | — |
Secondary
| Measure | Time frame |
|---|---|
| dose limited toxicity (DLT);the survival time of CD147-CART cells in vivo;the functional status of CD147-CART cells in vivo; | — |
Countries
China
Contacts
Public ContactJunhui Chen
Peking University Shenzhen Hospital
Outcome results
None listed