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CAR-T Cell Immunotherapy for HCC Targeting GPC3

Primary Purpose

GPC3 Positive Hepatocellular Carcinoma, CAR-T Cell Immunotherapy

Status

Withdrawn

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR-T cell immunotherapy

About this trial

This is an interventional treatment trial for GPC3 Positive Hepatocellular Carcinoma focused on measuring glypican-3(GPC3), chimeric antigen receptor-modified T cell(CAR-T), hepatocellular carcinoma(HCC)

Eligibility Criteria

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

Inclusion Criteria:

Age:18-70 years.
Gender:both.
GPC3 high expression hepatocellular carcinoma patients.
Non diffuse hepatocellular carcinoma，no extrahepatic metastasis or portal vein vascular invasion.
Degree of liver cirrhosis：class A or class B 7 according to Child-puge grading standard.
Routine blood test：white blood cell count（WBC)>=3×10^9/L, Lymphocyte percentage>=15%, hemoglobinHbo（Hb）>=90g/L, prothrombin time（PT） prolongation<=50% normal value, Cluster of differentiation 3(CD3) positive T cell count>=0.8×10^9/L.
Liver and Pancreatic function：Alanine aminotransferase/Aspartate transaminase(ALT/AST)<=5 times of the normal value, total bilirubin(TBiL)<=3.0mg/dL, albumin(ALB)>=35g/L, prothrombin time(PT):International Normalized Ratio(INR)<=1.7 or prothrombin time(PT) prolongation<=4s, Serum lipase<=1.5 times of the normal value, Serum amylase<=1.5 times of the normal value.
Renal function：Serum creatinine(SCr)<=221μmol/L(2.5mg/L).
Karnofsky Performance Status(KPS)>=60；Expected survival time>=12 weeks.
Peripheral venous access ；no contraindication of lymphocyte separation.
No other serious complications.
Voluntarily signed informed consent.

Exclusion Criteria:

Pregnant and lactating women.
Lymphocyte separation or peripheral venous access cannot be performed in patients .
Patients in the active stage of infection or with coagulation disorders.
Patients with a previous history of hepatic coma.
Patients with severe gastrointestinal ulcers or gastrointestinal bleeding.
Patients with organ transplantation or waiting for organ transplantation.
Patients with anticoagulant therapy.
Patients with antiplatelet therapy.
Serum sodium(Na)<125 mmol/L.
Serum potassium(K)<3.5 mmol/L(except patients up to the standards after the use of supplements).
Patients with organ failure：
1. cardiac function：level three or above according to New York Heart Association (NYHA) criteria.
2. liver function:class C or above according to Child-puge grading standard.
3. renal function:Chronic kidney disease(CKD) phase 4 or more; renal insufficiency phase Ⅲ or more.
4. pulmonary function：severe respiratory failure symptoms, involving other organs.
5. Brain function:central nervous system abnormalities or disturbance of consciousness.
Patients with non controlled infectious diseases,for example,HIV positive, syphilis, hepatitis A, hepatitis B, hepatitis C, hepatitis E virus (HEV) positive etc.
Patients used corticosteroids or other immunosuppressive agents in the past 4 weeks.
Patients with autoimmune disease.
Patients with previous history of gene therapy.
The actual transfection rate of T cells was lower than 30% or the proliferation was less than 5 times after costimulation.
Patients participated in other drug trials in the past 4 weeks.
Patients received radiation treatment in the past 4 weeks.
Patients do not meet the criteria above.

Sites / Locations

Central laboratory in Fuda cancer hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

CAR-T cell immunotherapy

no intervention

Arm Description

Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen by infusion.

no intervention

Outcomes

Primary Outcome Measures

Radiological assessment

Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan.

Secondary Outcome Measures

The safety of CAR-T cell immunotherapy (adverse events)

After CAR-T cell infusion,we will observe the potential adverse events related to the T-cell infusion such as high fever,jaundice, kidney failure and so on.

Peripheral blood tumor markers

tested regularly to reflect the role of the Chimeric Antigen Receptor-Modified T Cell in the removal of residual tumor cells.

CAR-T cell testing

The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival.

Full Information

NCT ID

NCT02723942

First Posted

March 20, 2016

Last Updated

July 14, 2020

Sponsor

Fuda Cancer Hospital, Guangzhou

1. Study Identification

Unique Protocol Identification Number

NCT02723942

Brief Title

CAR-T Cell Immunotherapy for HCC Targeting GPC3

Official Title

Chimeric Antigen Receptor-Modified T Cell (CAR-T) Immunotherapy for Hepatocellular Carcinoma (HCC) Targeting Glypican-3 (GPC3)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Project terminated due to revision of local regulations

Study Start Date

June 2015 (Actual)

Primary Completion Date

August 15, 2016 (Actual)

Study Completion Date

August 15, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fuda Cancer Hospital, Guangzhou

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to preliminarily evaluate the safety and efficacy of CAR-T cell immunotherapy for GPC3 positive hepatocellular carcinoma.

Detailed Description

Chimeric antigen receptor (CAR) is a recombinant receptor with both antigen-binding and T cell activating functions. Chimeric antigen receptor T cell Immunotherapy has more advantages compared with conventional immunotherapy, especially in dealing with patients of hematologic malignancies and solid malignant tumors.This study design a novel specific Chimeric antigen receptor targeting glypican-3(GPC3) antigen.After CAR-T cell infusion,At periodic intervals, the investigators will evaluate clinical symptoms Improved conditions of this disease.Through this study,the investigators will evaluate the safety and efficacy of CAR-T cell immunotherapy in treating with GPC3 positive malignant glioma patients.

6. Conditions and Keywords

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

GPC3 Positive Hepatocellular Carcinoma, CAR-T Cell Immunotherapy

Keywords

glypican-3(GPC3), chimeric antigen receptor-modified T cell(CAR-T), hepatocellular carcinoma(HCC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CAR-T cell immunotherapy

Arm Type

Experimental

Arm Description

Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen by infusion.

Arm Title

no intervention

Arm Type

No Intervention

Arm Description

no intervention

Intervention Type

Biological

Intervention Name(s)

CAR-T cell immunotherapy

Intervention Description

This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen.

Primary Outcome Measure Information:

Title

Radiological assessment

Description

Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

The safety of CAR-T cell immunotherapy (adverse events)

Description

After CAR-T cell infusion,we will observe the potential adverse events related to the T-cell infusion such as high fever,jaundice, kidney failure and so on.

Time Frame

4 weeks

Title

Peripheral blood tumor markers

Description

tested regularly to reflect the role of the Chimeric Antigen Receptor-Modified T Cell in the removal of residual tumor cells.

Time Frame

3 months

Title

CAR-T cell testing

Description

Time Frame

3 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: Age:18-70 years. Gender:both. GPC3 high expression hepatocellular carcinoma patients. Non diffuse hepatocellular carcinoma，no extrahepatic metastasis or portal vein vascular invasion. Degree of liver cirrhosis：class A or class B 7 according to Child-puge grading standard. Routine blood test：white blood cell count（WBC)>=3×10^9/L, Lymphocyte percentage>=15%, hemoglobinHbo（Hb）>=90g/L, prothrombin time（PT） prolongation<=50% normal value, Cluster of differentiation 3(CD3) positive T cell count>=0.8×10^9/L. Liver and Pancreatic function：Alanine aminotransferase/Aspartate transaminase(ALT/AST)<=5 times of the normal value, total bilirubin(TBiL)<=3.0mg/dL, albumin(ALB)>=35g/L, prothrombin time(PT):International Normalized Ratio(INR)<=1.7 or prothrombin time(PT) prolongation<=4s, Serum lipase<=1.5 times of the normal value, Serum amylase<=1.5 times of the normal value. Renal function：Serum creatinine(SCr)<=221μmol/L(2.5mg/L). Karnofsky Performance Status(KPS)>=60；Expected survival time>=12 weeks. Peripheral venous access ；no contraindication of lymphocyte separation. No other serious complications. Voluntarily signed informed consent. Exclusion Criteria: Pregnant and lactating women. Lymphocyte separation or peripheral venous access cannot be performed in patients . Patients in the active stage of infection or with coagulation disorders. Patients with a previous history of hepatic coma. Patients with severe gastrointestinal ulcers or gastrointestinal bleeding. Patients with organ transplantation or waiting for organ transplantation. Patients with anticoagulant therapy. Patients with antiplatelet therapy. Serum sodium(Na)<125 mmol/L. Serum potassium(K)<3.5 mmol/L(except patients up to the standards after the use of supplements). Patients with organ failure： cardiac function：level three or above according to New York Heart Association (NYHA) criteria. liver function:class C or above according to Child-puge grading standard. renal function:Chronic kidney disease(CKD) phase 4 or more; renal insufficiency phase Ⅲ or more. pulmonary function：severe respiratory failure symptoms, involving other organs. Brain function:central nervous system abnormalities or disturbance of consciousness. Patients with non controlled infectious diseases,for example,HIV positive, syphilis, hepatitis A, hepatitis B, hepatitis C, hepatitis E virus (HEV) positive etc. Patients used corticosteroids or other immunosuppressive agents in the past 4 weeks. Patients with autoimmune disease. Patients with previous history of gene therapy. The actual transfection rate of T cells was lower than 30% or the proliferation was less than 5 times after costimulation. Patients participated in other drug trials in the past 4 weeks. Patients received radiation treatment in the past 4 weeks. Patients do not meet the criteria above.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lizhi Niu, PhD

Organizational Affiliation

Fuda Cancer Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Central laboratory in Fuda cancer hospital

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

12. IPD Sharing Statement

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CAR-T Cell Immunotherapy for HCC Targeting GPC3

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