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GPC3-targeted CAR-T Cell for Treating GPC3 Positive Advanced HCC

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T cell immunotherapy
Sponsored by
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. GPC3 positive HCC, tumor size >= 5 cm, cannot receive standard treatment, Expected survival time>=3 months.
  2. Routine blood test: white blood cell count（WBC)>= 2.5×10^9/L, hemoglobin (Hb)>= 9.0 g/dL, blood platelet >= 60×10^9/L, Lymphocyte percentage>=15%.
  3. Blood biochemical parameters: ALB >= 30 g/L, ALT <= 5 times of the normal value, AST <= 5 times of the normal value, serum lipase<=1.5 times of the normal value, serum amylase<=1.5 times of the normal value， total bilirubin <= 2.5 times of the normal value.
  4. Prothrombin time INR < 1.7.
  5. Ejection fraction (EF) >= 55%, oxygen saturation (SO2) > 90%.
  6. No allergic reaction to contrast material.
  7. Karnofsky score >= 60%.
  8. Child-puge score <7.
  9. Peripheral venous access.
  10. Voluntarily signed informed consent.

Exclusion Criteria:

  1. Pregnancy or lactation.
  2. Systemic steroid treatment ( >prednisone equivalent/kg/day).
  3. Patients with previous history of cell immunotherapy or antibody therapy.
  4. Patients received radiotherapy/chemotherapy in the past 4 weeks.
  5. Patients are participating in other clinical trials.
  6. Patients with uncontrolled symptoms including infection, heart failure, arrhythmia.
  7. Patients with acute allergic reaction.
  8. History of liver transplantation.
  9. Patients with anticoagulant treatment.
  10. Patients with hepatic encephalopathy.
  11. Eligible for hepatectomy, liver transplantation or other standard treatment.
  12. Unstable gastrointestinal and respiratory bleeding.
  13. Active viral, fungal or bacterial infections.
  14. Heart failure classification (NYHA): II-IV.
  15. Patients are unable or unwilling to comply with the requirements of the study protocol.
  16. Patients do not meet the criteria above.

Sites / Locations

  • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T cells

Arm Description

CAR-T cells targeting GPC3 will be administered to enrolled patients with hepatocellular carcinoma.

Outcomes

Primary Outcome Measures

Number of patient with dose limiting toxicity
After each dose of T cell infusion, the adverse effects related to T cell therapy such as fever and jaundice are observed.

Secondary Outcome Measures

Radiological evaluation of tumor size after CAR- T immunotherapy
Evaluate the therapeutic effect of CAR-T immunotherapy radiological observation of the tumor size after infusion of CAR-T cells.
Peripheral tumor marker
After CAR-T cell infusion, alpha fetoprotein (AFP) will be tested regularly in blood.
Number of Peripheral CAR-T cell
The number and proliferation in vivo are tested with Flow Cytometry regularly.

Full Information

First Posted
October 8, 2019
Last Updated
March 1, 2021
Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
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1. Study Identification

Unique Protocol Identification Number
NCT04121273
Brief Title
GPC3-targeted CAR-T Cell for Treating GPC3 Positive Advanced HCC
Official Title
Clinical Study of GPC3-targeted Chimeric Antigen Receptor T Cells fo Treating Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 5, 2019 (Actual)
Primary Completion Date
October 1, 2021 (Anticipated)
Study Completion Date
November 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Patients with hepatocellular carcinoma (a type of primary liver cancers) are enrolls in this study. The cancer has progressed after standard treatment, or the patient cannot receive regular treatment. Investigator made a gene called chimeric antigen receptor derived from an antibody that recognizes Glypican 3, a protein detected in in a large proportion of hepatocellular carcinoma. The gene will introduce into T cell from patient's blood to make them recognize and kill cancer cells. The aim of this study is to evaluate the efficacy, tolerance and safety of chimeric antigen receptor-modified T (CAR-T) cell targeting Glypican 3 for advanced hepatocellular carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
chimeric antigen receptor T cell (CAR- T), glypican-3 (GPC3), hepatocellular carcinoma (HCC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T cells
Arm Type
Experimental
Arm Description
CAR-T cells targeting GPC3 will be administered to enrolled patients with hepatocellular carcinoma.
Intervention Type
Biological
Intervention Name(s)
CAR-T cell immunotherapy
Intervention Description
Patients enrolled will recieve three different doses of the CAR-T cell every two weeks as follows: Dose 1: 1x10^7/m2 Dose 2: 3x10^7/m2 Dose 3: 1x10^8/m2 The cell numbers are calculated according to CAR-positive T cells.
Primary Outcome Measure Information:
Title
Number of patient with dose limiting toxicity
Description
After each dose of T cell infusion, the adverse effects related to T cell therapy such as fever and jaundice are observed.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Radiological evaluation of tumor size after CAR- T immunotherapy
Description
Evaluate the therapeutic effect of CAR-T immunotherapy radiological observation of the tumor size after infusion of CAR-T cells.
Time Frame
3 months
Title
Peripheral tumor marker
Description
After CAR-T cell infusion, alpha fetoprotein (AFP) will be tested regularly in blood.
Time Frame
3 months
Title
Number of Peripheral CAR-T cell
Description
The number and proliferation in vivo are tested with Flow Cytometry regularly.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: GPC3 positive HCC, tumor size >= 5 cm, cannot receive standard treatment, Expected survival time>=3 months. Routine blood test: white blood cell count（WBC)>= 2.5×10^9/L, hemoglobin (Hb)>= 9.0 g/dL, blood platelet >= 60×10^9/L, Lymphocyte percentage>=15%. Blood biochemical parameters: ALB >= 30 g/L, ALT <= 5 times of the normal value, AST <= 5 times of the normal value, serum lipase<=1.5 times of the normal value, serum amylase<=1.5 times of the normal value， total bilirubin <= 2.5 times of the normal value. Prothrombin time INR < 1.7. Ejection fraction (EF) >= 55%, oxygen saturation (SO2) > 90%. No allergic reaction to contrast material. Karnofsky score >= 60%. Child-puge score <7. Peripheral venous access. Voluntarily signed informed consent. Exclusion Criteria: Pregnancy or lactation. Systemic steroid treatment ( >prednisone equivalent/kg/day). Patients with previous history of cell immunotherapy or antibody therapy. Patients received radiotherapy/chemotherapy in the past 4 weeks. Patients are participating in other clinical trials. Patients with uncontrolled symptoms including infection, heart failure, arrhythmia. Patients with acute allergic reaction. History of liver transplantation. Patients with anticoagulant treatment. Patients with hepatic encephalopathy. Eligible for hepatectomy, liver transplantation or other standard treatment. Unstable gastrointestinal and respiratory bleeding. Active viral, fungal or bacterial infections. Heart failure classification (NYHA): II-IV. Patients are unable or unwilling to comply with the requirements of the study protocol. Patients do not meet the criteria above.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Decai Yu, MD
Phone
8613701585023
Email
yudecai@nju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wenfang Tian, PhD
Phone
8613675104348
Email
tiancpu@163.com
Facility Information:
Facility Name
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210008
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenfang Tian, PhD
Phone
8613675104348
Email
tiancpu@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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GPC3-targeted CAR-T Cell for Treating GPC3 Positive Advanced HCC

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