Clinical trial NCT04121273: GPC3-targeted CAR-T Cell for Treating GPC3 Positive Advanced HCC
Official title: Clinical Study of GPC3-targeted Chimeric Antigen Receptor T Cells fo Treating Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: chimeric antigen receptor T cell (CAR- T)
glypican-3 (GPC3)
hepatocellular carcinoma (HCC)
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2019-10-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with hepatocellular carcinoma (a type of primary liver cancers) are enrolls in this study. The cancer has progressed after standard treatment, or the patient cannot receive regular treatment.

Investigator made a gene called chimeric antigen receptor derived from an antibody that recognizes Glypican 3, a protein detected in in a large proportion of hepatocellular carcinoma. The gene will introduce into T cell from patient's blood to make them recognize and kill cancer cells.

The aim of this study is to evaluate the efficacy, tolerance and safety of chimeric antigen receptor-modified T (CAR-T) cell targeting Glypican 3 for advanced hepatocellular carcinoma.


Eligibility criteria: Inclusion Criteria:

1. GPC3 positive HCC, tumor size \>= 5 cm, cannot receive standard treatment, Expected survival time\>=3 months.
2. Routine blood test: white blood cell count（WBC)\>= 2.5×10\^9/L, hemoglobin (Hb)\>= 9.0 g/dL, blood platelet \>= 60×10\^9/L, Lymphocyte percentage\>=15%.
3. Blood biochemical parameters: ALB \>= 30 g/L, ALT \<= 5 times of the normal value, AST \<= 5 times of the normal value, serum lipase\<=1.5 times of the normal value, serum amylase\<=1.5 times of the normal value， total bilirubin \<= 2.5 times of the normal value.
4. Prothrombin time INR \< 1.7.
5. Ejection fraction (EF) \>= 55%, oxygen saturation (SO2) \> 90%.
6. No allergic reaction to contrast material.
7. Karnofsky score \>= 60%.
8. Child-puge score \<7.
9. Peripheral venous access.
10. Voluntarily signed informed consent.

Exclusion Criteria:

1. Pregnancy or lactation.
2. Systemic steroid treatment ( \>prednisone equivalent/kg/day).
3. Patients with previous history of cell immunotherapy or antibody therapy.
4. Patients received radiotherapy/chemotherapy in the past 4 weeks.
5. Patients are participating in other clinical trials.
6. Patients with uncontrolled symptoms including infection, heart failure, arrhythmia.
7. Patients with acute allergic reaction.
8. History of liver transplantation.
9. Patients with anticoagulant treatment.
10. Patients with hepatic encephalopathy.
11. Eligible for hepatectomy, liver transplantation or other standard treatment.
12. Unstable gastrointestinal and respiratory bleeding.
13. Active viral, fungal or bacterial infections.
14. Heart failure classification (NYHA): II-IV.
15. Patients are unable or unwilling to comply with the requirements of the study protocol.
16. Patients do not meet the criteria above.

Primary outcomes:
measure: Number of patient with dose limiting toxicity
timeFrame: 2 months
Secondary outcomes:
measure: Radiological evaluation of tumor size after CAR- T immunotherapy
timeFrame: 3 months
measure: Peripheral tumor marker
timeFrame: 3 months
measure: Number of Peripheral CAR-T cell
timeFrame: 3 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
References: