CAR-T Cell Immunotherapy for HCC Targeting GPC3

• ClinicalTrials.gov Identifier: NCT02723942
• Recruitment Status: Withdrawn
• First Posted: March 31, 2016
• Last Update Posted: July 16, 2020
• Sponsor: Fuda Cancer Hospital, Guangzhou
• Information provided by (Responsible Party): Fuda Cancer Hospital, Guangzhou

Study Description

Brief Summary:

The purpose of this study is to preliminarily evaluate the safety and efficacy of CAR-T cell immunotherapy for GPC3 positive hepatocellular carcinoma.

Condition or disease	Intervention/treatment	Phase
GPC3 Positive Hepatocellular Carcinoma; CAR-T Cell Immunotherapy	Biological: CAR-T cell immunotherapy	Phase 1; Phase 2

Detailed Description:

Chimeric antigen receptor (CAR) is a recombinant receptor with both antigen-binding and T cell activating functions. Chimeric antigen receptor T cell Immunotherapy has more advantages compared with conventional immunotherapy, especially in dealing with patients of hematologic malignancies and solid malignant tumors.This study design a novel specific Chimeric antigen receptor targeting glypican-3(GPC3) antigen.After CAR-T cell infusion,At periodic intervals, the investigators will evaluate clinical symptoms Improved conditions of this disease.Through this study,the investigators will evaluate the safety and efficacy of CAR-T cell immunotherapy in treating with GPC3 positive malignant glioma patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Chimeric Antigen Receptor-Modified T Cell (CAR-T) Immunotherapy for Hepatocellular Carcinoma (HCC) Targeting Glypican-3 (GPC3)
• Actual Study Start Date: June 2015
• Actual Primary Completion Date: August 15, 2016
• Actual Study Completion Date: August 15, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: CAR-T cell immunotherapy; Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen by infusion.	Biological: CAR-T cell immunotherapy; This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen.
No Intervention: no intervention; no intervention

Outcome Measures

Primary Outcome Measures :

1. Radiological assessment [ Time Frame: 3 months ]
   Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan.

Secondary Outcome Measures :

1. The safety of CAR-T cell immunotherapy (adverse events) [ Time Frame: 4 weeks ]
   After CAR-T cell infusion,we will observe the potential adverse events related to the T-cell infusion such as high fever,jaundice, kidney failure and so on.
2. Peripheral blood tumor markers [ Time Frame: 3 months ]
   tested regularly to reflect the role of the Chimeric Antigen Receptor-Modified T Cell in the removal of residual tumor cells.
3. CAR-T cell testing [ Time Frame: 3 months ]
   The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age:18-70 years.
2. Gender:both.
3. GPC3 high expression hepatocellular carcinoma patients.
4. Non diffuse hepatocellular carcinoma，no extrahepatic metastasis or portal vein vascular invasion.
5. Degree of liver cirrhosis：class A or class B 7 according to Child-puge grading standard.
6. Routine blood test：white blood cell count（WBC)>=3×10^9/L, Lymphocyte percentage>=15%, hemoglobinHbo（Hb）>=90g/L, prothrombin time（PT） prolongation<=50% normal value, Cluster of differentiation 3(CD3) positive T cell count>=0.8×10^9/L.
7. Liver and Pancreatic function：Alanine aminotransferase/Aspartate transaminase(ALT/AST)<=5 times of the normal value, total bilirubin(TBiL)<=3.0mg/dL, albumin(ALB)>=35g/L, prothrombin time(PT):International Normalized Ratio(INR)<=1.7 or prothrombin time(PT) prolongation<=4s, Serum lipase<=1.5 times of the normal value, Serum amylase<=1.5 times of the normal value.
8. Renal function：Serum creatinine(SCr)<=221μmol/L(2.5mg/L).
9. Karnofsky Performance Status(KPS)>=60；Expected survival time>=12 weeks.
10. Peripheral venous access ；no contraindication of lymphocyte separation.
11. No other serious complications.
12. Voluntarily signed informed consent.

Exclusion Criteria:

1. Pregnant and lactating women.
2. Lymphocyte separation or peripheral venous access cannot be performed in patients .
3. Patients in the active stage of infection or with coagulation disorders.
4. Patients with a previous history of hepatic coma.
5. Patients with severe gastrointestinal ulcers or gastrointestinal bleeding.
6. Patients with organ transplantation or waiting for organ transplantation.
7. Patients with anticoagulant therapy.
8. Patients with antiplatelet therapy.
9. Serum sodium(Na)<125 mmol/L.
10. Serum potassium(K)<3.5 mmol/L(except patients up to the standards after the use of supplements).

11. Patients with organ failure：

    1. cardiac function：level three or above according to New York Heart Association (NYHA) criteria.
    2. liver function:class C or above according to Child-puge grading standard.
    3. renal function:Chronic kidney disease(CKD) phase 4 or more; renal insufficiency phase Ⅲ or more.
    4. pulmonary function：severe respiratory failure symptoms, involving other organs.
    5. Brain function:central nervous system abnormalities or disturbance of consciousness.
12. Patients with non controlled infectious diseases,for example,HIV positive, syphilis, hepatitis A, hepatitis B, hepatitis C, hepatitis E virus (HEV) positive etc.
13. Patients used corticosteroids or other immunosuppressive agents in the past 4 weeks.
14. Patients with autoimmune disease.
15. Patients with previous history of gene therapy.
16. The actual transfection rate of T cells was lower than 30% or the proliferation was less than 5 times after costimulation.
17. Patients participated in other drug trials in the past 4 weeks.
18. Patients received radiation treatment in the past 4 weeks.
19. Patients do not meet the criteria above.

Contacts and Locations

Locations

China, Guangdong

Central laboratory in Fuda cancer hospital

Guangzhou, Guangdong, China, 510000

Sponsors and Collaborators

Fuda Cancer Hospital, Guangzhou

Investigators

• Study Chair: Lizhi Niu, PhD; Fuda Cancer Hospital

More Information

• Responsible Party: Fuda Cancer Hospital, Guangzhou
• ClinicalTrials.gov Identifier: NCT02723942
• Other Study ID Numbers: CAR-T for GPC3+ HCC
• First Posted: March 31, 2016
• Last Update Posted: July 16, 2020
• Last Verified: July 2020

Keywords provided by Fuda Cancer Hospital, Guangzhou:

glypican-3(GPC3); chimeric antigen receptor-modified T cell(CAR-T); hepatocellular carcinoma(HCC)

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Immunomodulating Agents; Immunologic Factors; Physiological Effects of Drugs