AzTrials
AzTrials

Hepatocellular CarcinomaPhase 1/2NCT05323201

Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer

A Phase 1/2 study testing fhB7H3.CAR-Ts, Fludarabine and Cyclophosphamide in people with Hepatocellular Carcinoma, run by The Affiliated Hospital of Xuzhou Medical University at 1 site 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
Search all trials

Trial summary

This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating 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?
fhB7H3.CAR-Ts, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteChina
Study dates
10 Feb 2022to 10 Feb 2027
Phase
Phase 1/2
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects should be 18-70 years old.
  • Subject has adequate performance status as defined by ECOG score of≤ 2.
  • Expected life expectancy is no less than 12 weeks.
  • Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
  • Child-Pugh A, B grade.
  • Blood routine:
Show all 12Show fewer
  • white blood cell count≥ 2.5 × 10^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10^9 / L; lymphocyte proportion≥ 15 %;
  • Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:
  • ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
  • No allergic reaction to contrast agents.
  • Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
  • Patients or their legal guardians voluntarily participate in and sign the informed consent form.

Who cannot join

  • The subject is a pregnant or lactating woman.
  • The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
  • The subject has active infection or coagulation dysfunction.
  • Subjects with previous hepatic encephalopathy.
  • The subject is on anticoagulation or antiplatelet therapy.
  • The subject is an organ transplant or waiting for transplant.
Show all 16Show fewer
  • Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
  • The subjects are highly allergic or have a history of severe allergies.
  • The subject has received chemotherapy/radiotherapy within the past 4 weeks.
  • The subject has a history of cellular immunotherapy or antibody therapy.
  • The subject is receiving systemic hormone therapy.
  • Subjects with systemic infection or severe local infection requiring anti-infection treatment.
  • The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
  • The subject is participating in other clinical research.
  • The doctor believes that there are other reasons not to be included in the treatment.
  • Unwilling or unable to provide consent/assent for participation in the study.

Trial locations and contacts

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

China1 site, 1 recruiting

  • The Affiliated Hospital of Xuzhou Medical University

    Xuzhou, Jiangsu, 221002

    Yong Wang, M.D., +86-516-83353391, mumei20071115@163.com

    Yan Li, M.D., +86-516-83353391, 505620539@qq.com

    Recruiting

Other trials in China

About this study

Official title: A Single-Arm, Open-Label Study to Evaluate Safety and Efficacy of B7H3 or HBsAg Targeting CAR-T in Treating Advanced Hepatocellular Carcinoma

This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating hepatocellular carcinoma.

Read the detailed description

Chimeric antigen-modified T cells are genetically modified T cells that use gene transduction technology to introduce CARs, containing tumor antigen-specific recognition single-chain antibodies and T cell activation motifs, into patient T cells, so that these transduction CAR-T cells can directly recognize the specific antigen on tumor cells, thereby killing tumor cells.

Previous studies have confirmed that B7H3 is highly expressed in hepatocellular carcinoma cell lines, which is negatively correlated with the ten-year survival of patients. It is suggested that B7H3 is a specific therapeutic target for liver cancer.

The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells.

The investigators designed a single-arm open-label clinical study, the participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through transhepatic arterial infusion. From the day of infusion, participants' peripheral blood will be collected twice a week in the first month to monitor the survival of fhB7H3.CAR-Ts and evaluate the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until two year. Thereafter, annual follow-up will be completed for 5 years.

This is an investigator-initiated clinical study to assess clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent liver cancer patients in the future.

Being tested
fhB7H3.CAR-Ts, Fludarabine, Cyclophosphamide
Keywords
Fully human B7H3 CAR-T, Recurrent Advanced Hepatocellular Carcinoma
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • fhB7H3.CAR-TsBiological

    Also called B7H3 targeting chimeric antigen receptor T cells

    fhB7H3.CAR-Ts will be transhepatic arterial infused after lymphodepletion. Three dose levels will be evaluated: Dose Level 1 (1×10^6/kg), dose Level 2 (3×10^6/kg) and dose Level 3 (5×10^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10^6/kg /infusion) will be evaluated.

  • FludarabineDrug

    Also called FLUDARA

    30 mg/m2 i.v. for 3 consecutive days (Day -5~Day -3)

  • CyclophosphamideDrug

    Also called Cytoxan

    750 mg/m2 i.v. for once (Day -5)

Study groups in NCT05323201
Study groupRoleWhat they receive
fhB7H3.CAR-T cellsExperimentalIn phase I study , 9 enrolled patients diagnosed with advanced liver cancer will receive one-time transhepatic arterial infusion of fhB7H3.CAR-Ts at the doses of 1×10^6/kg, 3×10^6/kg and 5×10^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts.
Receives: Biological: fhB7H3.CAR-Ts; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Safety of fhB7H3.CAR-T cells

    Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.

    Measured: 1 month

  2. Objective response of fhB7H3.CAR-T cells

    Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

    Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis <10 mm).

    Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive.

    Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: 1 month

Secondary outcomes (1)

  1. In vivo persistence of fhB7H3.CAR-T cells

    Presence of CAR T cells in the peripheral blood will be assessed.

    Measured: 1 month

Timeline

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

  1. First posted12 Apr 2022
  2. Study start10 Feb 2022
  3. Primary completion10 Feb 2024 (estimated)
  4. Study completion10 Feb 2027 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05323201
Sponsor's protocol ID
XYFY2021-KL272-02
Status last verified
Feb 2022
First submitted
13 Feb 2022
Last updated
12 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing fhB7H3.CAR-Ts, Fludarabine and Cyclophosphamide in people with Hepatocellular Carcinoma, run by The Affiliated Hospital of Xuzhou Medical University at 1 site 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 12 inclusion and 16 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 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of fhB7H3.CAR-T cells (time frame: 1 month). 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 NCT05323201.

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 12 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in