Clinical trial NCT04417764: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Keywords: CRISPR Cas 9
TACE
PD-1 knockout engineered T cells
Advanced hepatocellular carcinoma
Locally administered treatment
Lead sponsor: Central South University
Sponsor class: OTHER
First posted: 2020-06-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: up to 2 years
Secondary outcomes:
measure: Response Rate
timeFrame: up to 12 months
measure: Time to First Response
timeFrame: up to 2 years
measure: Duration of Response
timeFrame: up to 2 years
measure: Progression Free Survival
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Changsha
country: China
facility: The 3rd Xiangya Hospital of Central South University
state: Hunan
Study officials:
References: