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

Phase 1

Recruiting

• Conditions: Advanced Hepatocellular Carcinoma
• Interventions: Procedure: Transcatheter arterial chemoembolization; Biological: PD-1 knockout engineered T cells

• Registration Number: NCT04417764
• Lead Sponsor: Central South University

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.

Study Timeline

• Study Start: 2019-06-20
• Study First Submitted: 2020-05-29
• Study First Submitted QC: 2020-06-02
• Study First Posted: 2020-06-05
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-09
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TACE combined PD-1 knockout T cell treatment	PD-1 knockout engineered T cells	-
TACE combined PD-1 knockout T cell treatment	Transcatheter arterial chemoembolization	-

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events	up to 2 years	Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	up to 2 years	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.
Overall Survival	up to 2 years	To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.
Time to First Response	up to 2 years	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).
Response Rate	up to 12 months	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.
Duration of Response	up to 2 years	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.

Trial Locations

Locations (1)

The 3rd Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China