Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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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
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Primary Objectives: To evaluate the safety of intravenous administration of the anti-GPC3 CAR-T cells in patients with HCC or lung squamous cell carcinoma To access the safety of anti-GPC3 CAR-T cells in HCC patients through catheter injection Secondary Objectives: To evaluate the efficacy of anti-GPC3 CAR-T cells in patients with advanced HCC or lung squamous cell carcinoma To monitor the serum cytokine and expression level of tumor markers such as AFP, CEA and GPC3 To assess the persistence in peripheral blood and intratumoral infiltration of anti-GPC3 CAR-T cells

Official Title
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Phase I Trial of Anti-GPC3 Chimeric T Cells for Subjects With GPC3-Positive Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-GPC3 CAR-T<br>Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion | Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs<br>* transcatheter arterial chemoembolization + CAR-T infusion<br>Drug: Fludarabine<br>* Fludarabine will be administered at dose of 25mg/m2/d<br>Drug: Cyclophosphamide<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Overall complete remission rate defined by the standard response criteria | Overall complete remission rate defined by the standard response criteria | 8 weeks | 
| Persistence: Duration of CAR-positive T cells in circulation | Duration of CAR-positive T cells in circulation | 6 months |