AzTrials
AzTrials

Hepatocellular CarcinomaPhase 1NCT03198546

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

A Phase 1 study testing GPC3 and/or TGFβ targeting CAR-T cells in people with Hepatocellular Carcinoma and Immunotherapy, run by Second Affiliated Hospital of Guangzhou Medical University at 2 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatocellular Carcinoma, Immunotherapy, CAR
What is being tested?
GPC3 and/or TGFβ targeting CAR-T cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesChina
Study dates
1 Jul 2017to 1 Aug 2036
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • patients with advanced HCC,which express GPC3 protein.
  • Life expectancy >12 weeks
  • Child-Pugh-Turcotte score <7
  • Adequate heart,lung,liver,kidney function
  • 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
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Who cannot join

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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Zhenfeng Zhang, MD,PhD contact

0086-020-34153532

zhangzhf@gzhmu.edu.cn

Peng Li, PhD contact

+86 20 32015300

lipeng@invivobio.com.cn

China2 sites, 2 recruiting

  • The First Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510072

    Xianhong Xiang, MD,PHD

    Yonghui Huang, MD,PHD

    Recruiting

  • The Second Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong, 510260

    Zhenfeng Zhang, MD,PhD, +86-020-34153532, zhangzhf@gzhmu.edu.cn

    Deji Chen, MD,PhD, +86-020-34153532, chendeji2003@163.com

    Recruiting

Other trials in China

About this study

Official title: CAR-T Cell Targeting GPC3 for Immunotherapy of Hepatocellular Carcinoma: Phase I Clinical Trial

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.

Read the 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 scfv/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 infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
  4. To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3-DAP10-CAR with knockdown of PD1/HPK1;
  5. Evaluate the clinical results as needed.
  6. Will also perform the similar clinical trial on lung squamous carcinoma with the GPC3 expression.
Being tested
GPC3 and/or TGFβ targeting CAR-T cells
Keywords
Hepatocellular carcinoma, immunotherapy, CAR-T cell therapy, GPC3 or TGFβ targeting, Phase I clinical study, squamous cell lung cancer, interventional radiology, IL7-CCL19-secreting, SCFV against PD1/CTLA4/Tigit, knockdown of PD1/HPK1, DAP10
Medical subject headings
Carcinoma, Hepatocellular, Simpson-Golabi-Behmel syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GPC3 and/or TGFβ targeting CAR-T cellsBiological

    Engineering GPC3 or/and TGFβ targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Tigit secreting vector into T cells with knockdown of PD1/HPK1, which are isolated from patients with advanced HCC, and then transfusing them back the patients.

Study groups in NCT03198546
Study groupRoleWhat they receive
CAR-T cell therapy groupOtherAppropriate patients who could benefit from the GPC3 and TGFβ targeting CAR-T cell therapy against HCC are chosen to be the CAR-T cell therapy group.
Receives: Biological: GPC3 and/or TGFβ targeting CAR-T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients with Dose Limiting Toxicity

    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.

    Measured: three months

Secondary outcomes (2)

  1. Percent of Patients with best response as either complete remission or partial remission.

    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.

    Measured: three months

  2. Median CAR-T cell persistence

    Median CAR-T cell persistence will be measured by quantitative rt-PCR.

    Measured: Five years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2017
  2. Study start1 Jul 2017
  3. Primary completion1 Aug 2029 (estimated)
  4. Study completion1 Aug 2036 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03198546
Sponsor's protocol ID
ZZCART-003
Status last verified
Jun 2024
First submitted
21 Jun 2017
Last updated
25 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, Lin S, Wang S, Wu Q, Liang Q, Liu Q, Peng M, Yu F, Weng J, Du X, Pei D, Liu P, Yao Y, Xue P, Li P. Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma. Front Immunol. 2017 Jan 11;7:690. doi: 10.3389/fimmu.2016.00690. eCollection 2016.

    PubMed 28123387

  • Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H, Huang Y, Wu Q, Li X, He B, Li T, Liang B, Zhang J, Cao B, Liu M, Feng Y, Ye X, Chen X, Wang L, Tian Y, Li H, Li J, Hu H, He J, Hu Y, Zhi C, Tang Z, Gong Y, Xu F, Xu L, Fan W, Zhao M, Chen D, Lian H, Yang L, Li P, Zhang Z. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol. 2021 Jul 29;14(1):118. doi: 10.1186/s13045-021-01128-9.

    PubMed 34325726

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GPC3 and/or TGFβ targeting CAR-T cells in people with Hepatocellular Carcinoma and Immunotherapy, run by Second Affiliated Hospital of Guangzhou Medical University at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhenfeng Zhang, MD,PhD (0086-020-34153532, zhangzhf@gzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients with Dose Limiting Toxicity (time frame: three months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03198546, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.

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