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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: CAR-T cell immunotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Decai Yu, MD; Phone Number: 8613701585023; Email: yudecai@nju.edu.cn
• Study Contact Backup: Name: Wenfang Tian, PhD; Phone Number: 8613675104348; Email: tiancpu@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
      • Contact: Wenfang Tian, PhD; Phone Number: 8613675104348; Email: tiancpu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T cells; CAR-T cells targeting GPC3 will be administered to enrolled patients with hepatocellular carcinoma.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2019
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 8, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 3, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma (HCC); chimeric antigen receptor T cell (CAR- T); glypican-3 (GPC3)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: v1.0 20180620

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No