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GPC3-T2-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression

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ClinicalTrials.gov Identifier: NCT03198546
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : November 26, 2019
Sponsor:
Collaborators:
Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
First Affiliated Hospital, Sun Yat-Sen University
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

Brief Summary:
The third/fourth generation of CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART )have been constructed and their anti-HCC function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test the anti-cancer function by the GPC3/TGFβ-CAR-T cells in human HCC patients with GPC3 expression. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/TGFβ-CAR-T cell immunotherapy on human will firstly be tested.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Immunotherapy CAR GPC3 Gene Inactivation T Cell Squamous Cell Lung Cancer Biological: GPC3 and/or TGFβ targeting CAR-T cells Phase 1

Detailed Description:
  1. Choose appropriate patients with advanced hepatocellular carcinoma,with written consent for this study;
  2. Perform biopsy to determine the expression of GPC3 of the tumor by western blotting or IHC;
  3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3/TGFβ targeting CAR (or/and cytokines-secreting), amplify the number of transfected T cells as needed,test the quality and killing activity of the GPC3/TGFβ-CART cells and then transplant back the patients via systemic or local injections, and follow up closely to collect related results as needed;
  4. Evaluate the clinical results as needed.
  5. Will also perform the similar clinical trial on lung squamous carcinoma with the same GPC3 expression.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
CAR-T cell therapy group
Appropriate patients who could benefit from the GPC3 or or TGFβ targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.
Biological: GPC3 and/or TGFβ targeting CAR-T cells
Engineering GPC3 or or TGFβ targeting CAR combined with/or without IL7-CCL19 secreting vector into T cells isolated from patients with advanced HCC, and then transfusing them back the patients.




Primary Outcome Measures :
  1. Number of Patients with Dose Limiting Toxicity [ Time Frame: three months ]
    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-T2-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.


Secondary Outcome Measures :
  1. Percent of Patients with best response as either complete remission or partial remission. [ Time Frame: three months ]
    Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

  2. Median CAR-T cell persistence [ Time Frame: Five years ]
    Median CAR-T cell persistence will be measured by quantitative rt-PCR.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. patients with advanced HCC,which express GPC3 protein.
  2. Life expectancy >12 weeks
  3. Child-Pugh-Turcotte score <7
  4. Adequate heart,lung,liver,kidney function
  5. Available autologous transduced T cells with greater than or equal to 20% expression of GPC3 CAR determined by flow-cytometry and killing of GPC3-positive targets greater than or equal to 20% in cytotoxicity assay
  6. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria:

  1. Had accepted gene therapy before;
  2. Tumor size more than 25cm;
  3. Severe virus infection such as HBV,HCV,HIV,et al
  4. Known HIV positivity
  5. History of liver transplantation
  6. Active infectious disease related to bacteria, virus,fungi,et al
  7. Other severe diseases that the investigators consider not appropriate;
  8. Pregnant or lactating women
  9. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
  10. Other conditions that the investigators consider not appropriate. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03198546


Contacts
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Contact: Zhenfeng Zhang, MD,PhD 0086-020-34153532 zhangzhf@gzhmu.edu.cn
Contact: Peng Li, PhD +86 20 32015300 lipeng@invivobio.com.cn

Locations
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China, Guangdong
The First Affiliated Hospital of Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510072
Contact: Xianhong Xiang, MD,PHD         
Contact: Yonghui Huang, MD,PHD         
The Second Affiliated Hospital of Guangzhou Medical University Recruiting
Guangzhou, Guangdong, China, 510260
Contact: Zhenfeng Zhang, MD,PhD    +86-020-34153532    zhangzhf@gzhmu.edu.cn   
Contact: Deji Chen, MD,PhD    +86-020-34153532    chendeji2003@163.com   
Sponsors and Collaborators
Second Affiliated Hospital of Guangzhou Medical University
Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
First Affiliated Hospital, Sun Yat-Sen University
Investigators
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Principal Investigator: Zhenfeng Zhang, MD,PhD Second Affiliated Hospital of Guangzhou Medical University

Publications of Results:
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Responsible Party: Second Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT03198546     History of Changes
Other Study ID Numbers: CAR-T on HCC
First Posted: June 26, 2017    Key Record Dates
Last Update Posted: November 26, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Second Affiliated Hospital of Guangzhou Medical University:
Hepatocellular carcinoma
immunotherapy
CAR-T cell therapy
GPC3 or TGFβ targeting
Phase I clinical study
squamous cell lung cancer
interventional radiology
IL7-CCL19-secreting
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Immunologic Factors
Physiological Effects of Drugs