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

NCT ID: NCT04417764

Last Updated: 2023-02-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-20
• Study Completion Date: 2024-12-31

Brief 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.

Detailed 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.

Conditions

Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TACE combined PD-1 knockout T cell treatment

Group Type: EXPERIMENTAL

Transcatheter arterial chemoembolization

Intervention Type: PROCEDURE

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

PD-1 knockout engineered T cells

Intervention Type: BIOLOGICAL

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.

Interventions

Transcatheter arterial chemoembolization

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

Intervention Type: PROCEDURE

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central South University

OTHER

Sponsor Role: lead

Responsible Party

Wei Wang,MD

Principal for The Institute for Cell Transplantation and Gene Therapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The 3rd Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Wang, MD

Role: CONTACT

cjr.wangwei@vip.163.com

86-0731-88618411

Facility Contacts

Xiaoqian Ma, MD

Role: primary

85316745@qq.com

86-0731-88618413

Other Identifiers

CellTransplant&GeneTherapy2020

Identifier Type: -

Identifier Source: org_study_id