Hepatocellular Carcinoma
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety and efficacy of anti-GPC3 scFv-41BB-CD3ζ-tEGFR chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating patients with GPC3-positive advanced hepatocellular carcinoma (HCC).
Detailed description
Primary Objectives: 1. To evaluate the safety of intravenous administration of the anti-GPC3 CAR-T cells in patients with HCC or lung squamous cell carcinoma 2. To access the safety of anti-GPC3 CAR-T cells in HCC patients through catheter injection Secondary Objectives: 1. To evaluate the efficacy of anti-GPC3 CAR-T cells in patients with advanced HCC or lung squamous cell carcinoma 2. To monitor the serum cytokine and expression level of tumor markers such as AFP, CEA and GPC3 3. To assess the persistence in peripheral blood and intratumoral infiltration of anti-GPC3 CAR-T cells
Interventions
BIOLOGICALRetroviral vector-transduced autologous T cells to express anti-GPC3 CARs
transcatheter arterial chemoembolization + CAR-T infusion
DRUGFludarabine
Fludarabine will be administered at dose of 25mg/m2/d
DRUGCyclophosphamide
Cyclophosphamide will be administered at dose of 40mg/kg for 1 day and then fludarabine will be given for the next 5 days and then the T cells will be administered
Sponsors
Xinqiao Hospital of Chongqing
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Expected to survive more than 3 months * PS 0-2 * Immunohistochemistry was confirmed to be GPC3 positive hepatocellular carcinoma * Patients with no ability to receive TACE combined with sorafenib * WBC\>3.5×1e+9/L,Hb\>90g/L,PLT\>75×1e+9/L * HBV DNA copy number less than 100/ml * ALT≤5ULN, AST≤5ULN, TB≤1.5ULN, ALB≥35g/L * Understand this test and have signed informed consent
Exclusion criteria
* Hepatic encephalopathy, autoimmune diseases, or any uncontrolled active disease that hinders participation in the trial * Decompensated liver cirrhosis, liver function Child-pugh C grade * Portal vein tumor thrombus, arterial portal fistula, hepatic arteriovenous * Long-term use of immunosuppressive agents after organ transplantation * Screening indicated that the target cell transfection rate was less than 30% * Invasive pulmonary embolism, deep venous thrombosis, or other major arterial / venous thromboembolic events occurred 30 days or 30 days prior to randomization * Subjects had an active or uncontrollable infection requiring systemic therapy 14 days or 14 days prior to randomization * Pregnant or lactating subjects * In the opinion of the investigator, the presence of a medical history or a history of mental state may increase the number of subjects associated with the risk factors associated with the study or study drug administration * Subjects who have signed a written consent or who are in compliance with the study procedure; or who are unwilling or unable to comply with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | 4 weeks | Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Overall complete remission rate defined by the standard response criteria | 8 weeks | Overall complete remission rate defined by the standard response criteria |
| Persistence: Duration of CAR-positive T cells in circulation | 6 months | Duration of CAR-positive T cells in circulation |
Countries
China
Outcome results
None listed