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

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04121273
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 24.9
• Patients Per Site Per Month: 0.8

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Biological: CAR-T cell immunotherapy	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Study of GPC3-targeted Chimeric Antigen Receptor T Cells fo Treating Advanced Hepatocellular Carcinoma
• Actual Study Start Date: Oct 5, 2019
• Anticipated Primary Completion Date: Oct 1, 2021
• Anticipated Study Completion Date: Nov 1, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Number of patient with dose limiting toxicity [2 months]

   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

1. Radiological evaluation of tumor size after CAR- T immunotherapy [3 months]

   Evaluate the therapeutic effect of CAR-T immunotherapy radiological observation of the tumor size after infusion of CAR-T cells.

2. Peripheral tumor marker [3 months]

   After CAR-T cell infusion, alpha fetoprotein (AFP) will be tested regularly in blood.

3. Number of Peripheral CAR-T cell [3 months]

   The number and proliferation in vivo are tested with Flow Cytometry regularly.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China	210008

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Beicheng Sun, Director of Hepatobiliary Surgery, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• ClinicalTrials.gov Identifier: NCT04121273
• Other Study ID Numbers: v1.0 20180620
• First Posted: Oct 9, 2019
• Last Update Posted: Mar 3, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Beicheng Sun, Director of Hepatobiliary Surgery, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: chimeric antigen receptor T cell (CAR- T); glypican-3 (GPC3); hepatocellular carcinoma (HCC)
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

No Results Posted as of Mar 3, 2021