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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03084380
• Other study ID #: GPC3CAR
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: March 5, 2017
• Last updated: March 17, 2017
• Start date: June 1, 2017
• Est. completion date: May 31, 2020

Study information

• Verified date: March 2017
• Source: Xinqiao Hospital of Chongqing
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: May 31, 2020
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs
transcatheter arterial chemoembolization + CAR-T infusion

Drug:
• Fludarabine
Fludarabine will be administered at dose of 25mg/m2/d
• Cyclophosphamide
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

Locations

Country	Name	City	State
China	Department of Oncology, Xinqiao Hospital	ChongQing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Xinqiao Hospital of Chongqing

Country where clinical trial is conducted

China, 

Outcome

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