TACE Combined With PD-1 Knockout Engineered T Cell in Advanced Hepatocellular Carcinoma.

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

Safety and Effect Assessment of TACE in Combination With Autologous PD-1 Knockout Engineered T Cells by Percutaneous Infusion in the Paitents With Advanced Hepatocellular Carcinoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04417764
• Other study ID #: CellTransplant&GeneTherapy2020
• Status: Recruiting
• Phase: Phase 1
• Start date: June 20, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2023
• Source: Central South University
• Contact: Wei Wang, MD
• Phone: 86-0731-88618411
• Email: cjr.wangwei[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and effect of transcatheter arterial chemoembolization (TACE)combined with percutaneous transhepatic PD-1 knockout engineered T cell infusion in the Paitents with advanced hepatocellular carcinoma(HCC). Blood and tissue samples will also be collected for research purposes.

Description:

This is a clinical study to investigate the safety and effect of transcatheter arterial chemoembolization (TACE) in combination with PD-1 knockout engineered T cells in the Paitents with advanced hepatocellular carcinoma. TACE would block the blood supply of the tumor to achieve ischemic, hypoxic andnecrotic effects. The PD-1 knockout engineered T cells were also prepared from autologous origin using CRISPR Cas9 technology. The patients performed one TACE treatment followed by 3 cycles of PD-1 edited T cells by percutaneous infusion in the peripheral of tumor under the guide of CT every four weeks. The safety and clinical efficacy will be evaluated. biomarkers and immunological markers will be monitored.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with unresectable hepatocellular carcinoma;

2. More than 18 years old;

3. Patients diagnosed with hepatocellular carcinoma by histopathology or imagings;

4. Liver function ChildPugh =7 points, Physical strength score ECOG-pts 0-1 points;

5. Maximum tumor diameter =10cm, tumor number =10, no vascular invasion or extrahepatic metastasis;

6. Other organs of the whole body function well;

7. Sign the informed consent;

8. Passed the review by the ethics committee.

Exclusion Criteria:

1. Less than 18 or more than 70 years old;

2. Lack of autonomous decision-making ability;

3. ECOG score >2, cachexia or multiple organ failure;

4. Metastases; The tumor was diffuse or metastasized widely and the expected survival time was less than 3 months.

5. Uncorrectable coagulation dysfunction with a history of bleeding; Organ transplant;

6. Patients with severe autoimmune diseases; Iodine contrast agent allergy; High allergic constitution;

7. The main portal vein was completely blocked by cancer embolism, with little collateral vascular formation;

8. Severe infection; AIDS, syphilis infection;

9. T cell lymphoma;

10. Patients with mental illness, severe trauma or other stress conditions;

11. Pregnant or nursing women;

12. Abnormal peripheral blood routine detection;

13. Failing to comply with the study protocol to complete the diagnosis and treatment project; Failed ethics committee review.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Procedure:
• Transcatheter arterial chemoembolization
The patients are plan to operated by Transcatheter arterial chemoembolization(TACE).

Biological:
• PD-1 knockout engineered T cells
The PD-1 knockout engineered T cells are prepared from autologous origin using CRISPR Cas9 technology. The patients are plan to receive 3 or more cycles of PD-1 knockout engineered T cells infusion by percutaneous fine needle liver puncture with a 4-weeks interval. A total of 1 to 3× 10^9 PD-1 edited T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.

Locations

Country	Name	City	State
China	The 3rd Xiangya Hospital of Central South University	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events	Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.	up to 2 years
Secondary	Response Rate	To evaluate the objective response rate (ORR) ,refers to the proportion of patients whose tumors shrink to a certain extent and remain unchanged for a certain period of time, including patients with CR+PR.Tumors are assessed at baseline, the 8th week, the 16th week,the 24th week, and once every 12 weeks during the treatment and follow-up period per RECIST1.1.	up to 12 months
Secondary	Time to First Response	To evaluate time to first response, defined as the time from the first cell infusion to the first observed complete response (CR) or partial response (PR).	up to 2 years
Secondary	Duration of Response	To evaluate the duration of response (DOR), defined as the time from the first observed CR or PR to the first observed PD or death from any cause.	up to 2 years
Secondary	Progression Free Survival	To evaluate the progression free survival (PFS), defined as the time from the first cell infusion to the first observed PD or death from any cause.	up to 2 years
Secondary	Overall Survival	To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.	up to 2 years