Clinical Trials /

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

NCT03084380

Description:

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).

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC)
  • Official Title: Phase I Trial of Anti-GPC3 Chimeric T Cells for Subjects With GPC3-Positive Advanced Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: GPC3CAR
  • NCT ID: NCT03084380

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
Retroviral vector-transduced autologous T cells to express anti-GPC3 CARsanti-GPC3 CAR-T
Fludarabineanti-GPC3 CAR-T
Cyclophosphamideanti-GPC3 CAR-T

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
anti-GPC3 CAR-TExperimentalTranscatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        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
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Xinqiao Hospital of Chongqing

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