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

Primary Purpose

Hepatocellular Carcinoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs

Fludarabine

Cyclophosphamide

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Oncology, Xinqiao Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-GPC3 CAR-T

Arm Description

Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Efficacy: Overall complete remission rate defined by the standard response criteria

Overall complete remission rate defined by the standard response criteria

Persistence: Duration of CAR-positive T cells in circulation

Duration of CAR-positive T cells in circulation

Full Information

NCT ID

NCT03084380

First Posted

March 5, 2017

Last Updated

March 17, 2017

Sponsor

Xinqiao Hospital of Chongqing

1. Study Identification

Unique Protocol Identification Number

NCT03084380

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Unknown status

Study Start Date

June 1, 2017 (Anticipated)

Primary Completion Date

May 31, 2019 (Anticipated)

Study Completion Date

May 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Xinqiao Hospital of Chongqing

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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: 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

anti-GPC3 CAR-T

Arm Type

Experimental

Arm Description

Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion

Intervention Type

Biological

Intervention Name(s)

Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs

Intervention Description

transcatheter arterial chemoembolization + CAR-T infusion

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

Fludarabine will be administered at dose of 25mg/m2/d

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

Description

Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Efficacy: Overall complete remission rate defined by the standard response criteria

Description

Overall complete remission rate defined by the standard response criteria

Time Frame

8 weeks

Title

Persistence: Duration of CAR-positive T cells in circulation

Description

Duration of CAR-positive T cells in circulation

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

Department of Oncology, Xinqiao Hospital

City

ChongQing

State/Province

Chongqing

ZIP/Postal Code

400037

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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