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

Primary Purpose

Advanced Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Transcatheter arterial chemoembolization
PD-1 knockout engineered T cells
Sponsored by
Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma focused on measuring CRISPR Cas 9, TACE, PD-1 knockout engineered T cells, Advanced hepatocellular carcinoma, Locally administered treatment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The 3rd Xiangya Hospital of Central South UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TACE combined PD-1 knockout T cell treatment

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Adverse Events
Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.

Secondary Outcome Measures

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.
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).
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.
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.
Overall Survival
To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.

Full Information

First Posted
May 29, 2020
Last Updated
February 7, 2023
Sponsor
Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT04417764
Brief Title
TACE Combined With PD-1 Knockout Engineered T Cell in Advanced Hepatocellular Carcinoma.
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2019 (Actual)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma
Keywords
CRISPR Cas 9, TACE, PD-1 knockout engineered T cells, Advanced hepatocellular carcinoma, Locally administered treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TACE combined PD-1 knockout T cell treatment
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Transcatheter arterial chemoembolization
Intervention Description
The patients are plan to operated by Transcatheter arterial chemoembolization(TACE).
Intervention Type
Biological
Intervention Name(s)
PD-1 knockout engineered T cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
up to 12 months
Title
Time to First Response
Description
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).
Time Frame
up to 2 years
Title
Duration of Response
Description
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.
Time Frame
up to 2 years
Title
Progression Free Survival
Description
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.
Time Frame
up to 2 years
Title
Overall Survival
Description
To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with unresectable hepatocellular carcinoma; More than 18 years old; Patients diagnosed with hepatocellular carcinoma by histopathology or imagings; Liver function ChildPugh ≤7 points, Physical strength score ECOG-pts 0-1 points; Maximum tumor diameter ≤10cm, tumor number ≤10, no vascular invasion or extrahepatic metastasis; Other organs of the whole body function well; Sign the informed consent; Passed the review by the ethics committee. Exclusion Criteria: Less than 18 or more than 70 years old; Lack of autonomous decision-making ability; ECOG score >2, cachexia or multiple organ failure; Metastases; The tumor was diffuse or metastasized widely and the expected survival time was less than 3 months. Uncorrectable coagulation dysfunction with a history of bleeding; Organ transplant; Patients with severe autoimmune diseases; Iodine contrast agent allergy; High allergic constitution; The main portal vein was completely blocked by cancer embolism, with little collateral vascular formation; Severe infection; AIDS, syphilis infection; T cell lymphoma; Patients with mental illness, severe trauma or other stress conditions; Pregnant or nursing women; Abnormal peripheral blood routine detection; Failing to comply with the study protocol to complete the diagnosis and treatment project; Failed ethics committee review.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Wang, MD
Phone
86-0731-88618411
Email
cjr.wangwei@vip.163.com
Facility Information:
Facility Name
The 3rd Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoqian Ma, MD
Phone
86-0731-88618413
Email
85316745@qq.com

12. IPD Sharing Statement

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

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