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Hepatocellular CarcinomaPhase 1NCT03349255

Clinical Study of ET1402L1-CAR T Cells in AFP Expressing Hepatocellular Carcinoma

A Phase 1 study testing autologous ET1402L1-CART cells in people with Hepatocellular Carcinoma and Liver Cancer, run by Aeon Therapeutics (Shanghai) Co., Ltd. at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
autologous ET1402L1-CART cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteChina
Study dates
6 Oct 2017to 10 Jan 2019
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • AFP-expressing HCC and serum AFP >100 ng/mL.
  • Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 20 mm.
  • Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
  • Child-Pugh score of A or B
  • Life expectancy > 4 months
  • Age at time of enrollment is ≥18 years of age.
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  • KPS ≥70%
  • Adequate organ function as defined below:
  • A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute.
  • Patients must have a serum direct bilirubin ≤2 x ULN, ALT and AST ≤5 times the institutional upper limits of normal.
  • Ejection Fraction measured by echocardiogram or MUGA >45% (evaluation done within 6 weeks of screening does not need to be repeated)
  • DLCO or FEV1 >45% predicted
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
  • Platelet count ≥ 50,000/mm3 (10^9/L)
  • Negative serum pregnancy test for women with childbearing potential
  • Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • Patients with decompensated cirrhosis: Child-Pugh Score C
  • Patients with an organ transplantation history
  • Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
  • Patients with dependence on corticosteroids
  • Patients with active autoimmune diseases requiring systemic immunosuppressive therapy
  • Patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery
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  • Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
  • Patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.).
  • Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. Patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled.
  • Patients with other uncontrolled diseases, such as active infections:
  • Acute or chronic active hepatitis B or hepatitis C.
  • HIV-infection
  • Women who are pregnant

Trial locations and contacts

1 site in 1 country.

China1 site

  • Renmin Hospital of Wuhan University

    Wuhan, Hubei, 430060

Other trials in China

About this study

Official title: Phase 1, Open-label, Two Routes IV and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-CAR T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC

Read the detailed description

The molecular target for ET1402L1-CART is alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ET1402L1-CART is a second generation (CD28/CD3ζ) chimeric antigen receptor (CAR) engineered with a human single-chain variable antibody fragments (scFv) against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-CART-cells in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Patients with lesion(s) localized in liver will be enrolled in the IA arm, with the ET1402L1-CART-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the IV arm, with the ET1402L1-CART-cells administered through intravenous infusion.

Being tested
autologous ET1402L1-CART cells
Keywords
alpha-fetoprotein, AFP, HCC, CAR T cell therapy
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

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

  • autologous ET1402L1-CART cellsBiological

    Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1)-CAR expression construct

Study groups in NCT03349255
Study groupRoleWhat they receive
intravenous (i.v.) armExperimentalautologous ET1402L1-CART cells administered by intravenous (IV) infusion
Receives: Biological: autologous ET1402L1-CART cells
intra-hepatic artery (i.a.) armExperimentalautologous ET1402L1-CART cells administered by intra-hepatic artery (IA) infusion
Receives: Biological: autologous ET1402L1-CART 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 ET1402L1-CART-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.

    Measured: 28 days up to 2 years

  2. Toxicity profile of ET1402L1-CART-cell treatment

    Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET1402L1-CART T cells related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits.

    Measured: 28 days up to 2 years

Secondary outcomes (9)

  1. Rate of disease response by RECIST in the liver

    Response rates will be estimated as the percent of patients with objective response (OR), complete remission (CR), partial response (PR), stable disease (SD), no response (NR), overall survival (OS).

    Measured: 2 years

  2. Rate of disease response by RECIST at non-liver sites

    Response rates will be estimated as the percent of patients with objective response (OR), complete remission (CR), partial response (PR), stable disease (SD), no response (NR), overall survival (OS).

    Measured: 2 years

  3. Anti-tumor responses

    Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years

    Measured: 4 months, 1 year, 2 years

  4. AFP serum levels

    Percent change compared to the baseline

    Measured: 2 years

  5. CART cell engraftment

    Number and % of ET1402L1-CART cells in peripheral blood will be presented as Time to peak, Time to baseline level and the overall exposure will be presented as area under curve (AUC).

    Measured: 2 years

  6. AFP expression in tumors

    Percent of AFP-positive cells in randomly selected fields in tumor biopsies

    Measured: 4-8 weeks

  7. Tmax of serum cytokine levels

    Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as time to peak level.

    Measured: 24 weeks

  8. Time to baseline for serum cytokine levels

    Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as Time to baseline.

    Measured: 24 weeks

  9. AUC of serum cytokine levels

    Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as area under curve (AUC).

    Measured: 24 weeks

Timeline

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

  1. First posted21 Nov 2017
  2. Study start6 Oct 2017
  3. Primary completion10 Jan 2019
  4. Study completion10 Jan 2019

Why it stopped: Will study new T-cell construct for the same indication

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03349255
Sponsor's protocol ID
ETCH17AFPCAR101
Status last verified
Jun 2019
First submitted
24 Oct 2017
Last updated
1 Jul 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing autologous ET1402L1-CART cells in people with Hepatocellular Carcinoma and Liver Cancer, run by Aeon Therapeutics (Shanghai) Co., Ltd. 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 16 inclusion and 13 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: stopped early, as of the sponsor's last update on 1 Jul 2019. 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 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 was stopped early (reason given: Will study new T-cell construct for the same indication). Results are not available in the source record.

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?

Number of patients with dose-limiting toxicity (time frame: 28 days up to 2 years). 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 NCT03349255.

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 1 Jul 2019.

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