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

Phase 1

• Conditions: Hepatocellular Carcinoma
• Interventions: Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT03084380
• Lead Sponsor: Xinqiao Hospital of Chongqing

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

Study Timeline

• Status Verified: 2017-03
• Study First Submitted: 2017-03-05
• Study First Submitted QC: 2017-03-17
• Last Update Submitted: 2017-03-17
• Study First Posted: 2017-03-20
• Last Update Posted: 2017-03-20
• Study Start: 2017-06-01
• Primary Completion: 2019-05-31
• Study Completion: 2020-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-GPC3 CAR-T	Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs	Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
anti-GPC3 CAR-T	Fludarabine	Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
anti-GPC3 CAR-T	Cyclophosphamide	Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Persistence: Duration of CAR-positive T cells in circulation	6 months	Duration of CAR-positive T cells in circulation
Efficacy: Overall complete remission rate defined by the standard response criteria	8 weeks	Overall complete remission rate defined by the standard response criteria

Trial Locations

Locations (1)

Department of Oncology, Xinqiao Hospital; 🇨🇳 ChongQing, Chongqing, China