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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Transcatheter arterial chemoembolization; Biological: PD-1 knockout engineered T cells

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Wang, MD; Phone Number: 86-0731-88618411; Email: cjr.wangwei@vip.163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • The 3rd Xiangya Hospital of Central South University
      • Contact: Xiaoqian Ma, MD; Phone Number: 86-0731-88618413; Email: 85316745@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: TACE combined PD-1 knockout T cell treatment

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Overall Survival	To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.	up to 2 years

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 20, 2019
• Primary Completion (ANTICIPATED): December 30, 2024
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (ACTUAL): June 5, 2020

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: TACE; CRISPR Cas 9; PD-1 knockout engineered T cells; Advanced hepatocellular carcinoma; Locally administered treatment
• 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: CellTransplant&GeneTherapy2020

Drug and device information, study documents

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