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

Hepatocellular Carcinoma Clinical Trial

Official title:

Clinical Study of GPC3-targeted Chimeric Antigen Receptor T Cells fo Treating Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04121273
• Other study ID #: v1.0 20180620
• Status: Recruiting
• Phase: Phase 1
• Start date: October 5, 2019
• Est. completion date: November 1, 2021

Study information

• Verified date: March 2021
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Decai Yu, MD
• Phone: 8613701585023
• Email: yudecai[@]nju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 1, 2021
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• CAR-T cell immunotherapy
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.

Locations

Country	Name	City	State
China	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 months
Secondary	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.	3 months
Secondary	Peripheral tumor marker	After CAR-T cell infusion, alpha fetoprotein (AFP) will be tested regularly in blood.	3 months
Secondary	Number of Peripheral CAR-T cell	The number and proliferation in vivo are tested with Flow Cytometry regularly.	3 months