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Hepatocellular CarcinomaPhase 1NCT03884751

Chimeric Antigen Receptor T Cells Targeting Glypican-3

A Phase 1 study testing CAR-GPC3 T Cells in people with Hepatocellular Carcinoma, run by CARsgen Therapeutics Co., Ltd. at 6 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients with Advanced Hepatocellular Carcinoma Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
CAR-GPC3 T Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
6 sitesChina
Study dates
15 Aug 2019to 3 Dec 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 to 70 years, male or female;
  • Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology who are not suitable for surgery or local treatment (including ablation, intervention, and radiotherapy), have developed progressive disease or intolerability after standard systemic therapies (including but not limited to systemic chemotherapy, molecular targeted therapy) and have no effective treatment at the time of enrollment;
  • According to RECIST 1.1, patients have at least one evaluable target lesion, defined as: the longest diameter of non-lymph node lesion ≥ 10 mm, or the shortest diameter of lymph node lesion ≥ 15 mm); hepatic lesions require arterial phase contrast enhancement;
  • In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
  • According to Barcelona Clinic Liver Cancer staging(BCLC), the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
  • Expected survival is > 12 weeks;
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  • Cirrhosis status Child-Pugh score: Grade A;
  • Eastern Cooperative Oncology Group(ECOG) Performance Status score: 0 to 1 point;
  • Without active hepatitis B and/or Hepatitis C;
  • Have venous accesses for pheresis;
  • Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment;
  • Adequate liver, renal, cardiovascular, respiratory function;
  • Subjects of childbearing age must undergo a serum pregnancy test within 14 days before the initiation of the study and the result must be negative. In addition, they should be willing to use a reliable method of contraception during the trial (within 24 months (M24) after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial;
  • Understand and sign informed consent.

Who cannot join

  • Pregnant or breast-feeding women;
  • HCV-RNA(Hepatitis C Virus RNA ), HIV antibodies or Syphilis Serological tests are positive;
  • HBV（Hepatitis B） and HCV(Hepatitis C virus ) infection exist simultaneously;
  • Any uncontrollable active infection
  • Patients who had received systemic steroids or other immunosuppressive agents
  • Previous or present hepatic encephalopathy;
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  • Current clinically significant ascites;
  • ≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
  • Metastases to the central nervous system and clinically significant central nervous system diseases;
  • Patients with existing heart disease in need of treatment or hypertension that be poorly controlled
  • Patients with known active autoimmune diseases which require to be treated with immunosuppressive agents including biological agents;
  • Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
  • Patients with local treatments such as surgical treatment, interventional therapy, radiotherapy, ablation or systemic chemotherapy were performed for the studied disease within 2 weeks prior to apheresis;Or received immunotherapy (PD-1/ PD-L1 monoclonal antibody, see Section 15) or any Chinese herbal or proprietary medicine for the control of liver cancer within 1 week prior to apheresis;Or received sorafenib, regofenib, ramvastinib and other tyrosine kinase inhibitor targeted drugs within 1 week prior to apheresis;Targeted therapy with anti-angiogenic monoclonal antibodies such as bevacizumab or its analogue 4 weeks prior to apheresis;
  • Patiens with previous treatment with targeted GPC3, TCR-T or CAR-T;
  • Patients who previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks prior to apheresis;
  • Patients who had uncured malignant tumors in the past 5 years or at the same time, excluding in situ cervical cancer and skin basal cell carcinoma;
  • Other serious illnesses that may limit subjects to participate in the trial (such as poorly controlled diabetes mellitus, severe cardiac insufficiency , myocardial infarction or unstable arrhythmia or unstable angina pectoris within the last 6 months, lung embolism, chronic obstructive pulmonary diseases, interstitial pulmonary diseases,gastric ulcer, a history of gastrointestinal bleeding or a clear tendency to gastrointestinal bleeding;
  • According to the investigators' evaluation, patients are unable or unwilling to comply with the requirements of the study protocol.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

China6 sites

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510000

  • The First Affiliated Hospital Zhejiang University

    Hangzhou, Zhejiang, 310006

  • The 81st Hospital of Chinese PLA

    Nanjing, Jiangsu, 210002

  • Renji Hospital Shang Hai Jiaotong Unversity of Medicine

    Shanghai, Shanghai Municipality, 200001

  • Zhongshan Hospital of Fudan University

    Shanghai, Shanghai Municipality, 200001

  • The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450000

Other trials in China

About this study

Official title: A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients With Advanced Hepatocellular Carcinoma

A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients with Advanced Hepatocellular Carcinoma

Read the detailed description

This is a phase I open-label, single-arm, multicenter clinical trial designed to observe and evaluate the safety, cell metabolokinetics, and efficacy of CAR-GPC3 T cells infused intravenously at single escalating doses in patients with advanced hepatocellular carcinoma.

Primary objectives:

  • To evaluate the safety and tolerability of CAR-GPC3 T cells infused intravenously at escalating doses in patients with advanced hepatocellular carcinoma.

Secondary objectives：

  • To evaluate the metabolic kinetics of single infusion of CAR-GPC3 T cells
  • To evaluate the overall safety and tolerability of infusion of CAR-GPC3 T cells
  • To observe the efficacy of CAR-GPC3 T cells in the treatment of advanced hepatocellular carcinoma
Being tested
CAR-GPC3 T Cells
Keywords
Hepatocellular Carcinoma, CAR-T
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • CAR-GPC3 T CellsBiological

    Also called Chimeric Antigen Receptor T Cells Targeting Glypican-3

    CAR-GPC3 T Cells injection

Study groups in NCT03884751
Study groupRoleWhat they receive
CAR-GPC3 T CellsExperimentalThe subjects are enrolled into 2 dose levels cohorts in sequence
Receives: Biological: CAR-GPC3 T Cells

What is being measured

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

  1. Dose-limiting toxicity (DLT)

    Safety

    Measured: After 28 days of single infusion

  2. Maximum tolerated dose (MTD)

    tolerability

    Measured: After 28 days of single infusion

Secondary outcomes (9)

  1. Pharmacokinetics (the copies of cells in vivo)

    Pharmacokinetics is the"Implantation endpoint" which is defined as the number of copies of CAR-GPC3 DNA in peripheral blood at each visit after infusion until any two consecutive test results are negative or below the detection limit. It aims to calculate the Peak Plasma Concentration (Cmax)

    Measured: Day0~Week 26

  2. Pharmacokinetics ( the duration of survival of cells in vivo)

    Duration of CAR-GPC3 T cell persistence is the period from the day of infusion to the first negative test result or result lower than the detection limit.It aims to calculate the area under the plasma concentration versus time curve (AUC)

    Measured: Day0~Week 26

  3. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Adverse events up to 24 months of follow-up visit judged by the investigator to be associated with CAR-GPC3T cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.

    Measured: Month 24

  4. Antitumor efficacy-Progression-free survival (PFS)

    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.

    Measured: Month 24

  5. Antitumor efficacy-Duration of response (DOR)

    The period from the first evaluation of CR or PR to the first evaluation of PD(Progressive Disease) or death of any cause.

    Measured: Month 24

  6. Antitumor efficacy-Duration of disease control (DDC)

    The period from the first evaluation of CR, PR, or SD to the first evaluation of PD or any cause of death.

    Measured: Month 24

  7. Antitumor efficacy-Overall survival (OS)

    The period from the first infusion to any cause of death

    Measured: Month 24

  8. Antitumor efficacy-Objective response rate (ORR);

    The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation

    Measured: Month 24

  9. Antitumor efficacy-Disease control rate (DCR)

    The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%).

    Measured: Month 24

Timeline

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

  1. First posted21 Mar 2019
  2. Study start15 Aug 2019
  3. Primary completion28 May 2021
  4. Study completion3 Dec 2021

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03884751
Sponsor's protocol ID
CT011-HCC-01
Status last verified
Feb 2022
First submitted
25 Feb 2019
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAR-GPC3 T Cells in people with Hepatocellular Carcinoma, run by CARsgen Therapeutics Co., Ltd. at 6 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 14 inclusion and 18 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: finished, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (DLT) (time frame: After 28 days of single infusion). The study lists 2 primary outcomes in all. 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 NCT03884751.

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 24 Feb 2022.

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