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Hepatocellular CarcinomaEarly Phase 1NCT03888859

ET1402L1-ARTEMIS™2 T Cells in Alpha Fetoprotein (AFP) Expressing Hepatocellular Carcinoma

A Early Phase 1 study testing ET1402L1-ARTEMIS™ T cells -IV, ET1402L1-ARTEMIS™ T cells -intra-hepatic artery and ET1402L1-ARTEMIS™ T cells -Intratumoral Injections in people with Hepatocellular Carcinoma and Liver Cancer, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site 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

Clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of ET1402L1-ARTEMIS™2 T cells in patients with alpha fetoprotein positive (AFP+ ) hepatocellular carcinoma (HCC). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
ET1402L1-ARTEMIS™ T cells -IV, ET1402L1-ARTEMIS™ T cells -intra-hepatic artery and ET1402L1-ARTEMIS™ T cells -Intratumoral Injections
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
6 Dec 2017to 8 Dec 2020
Phase
Early 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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • AFP-expressing HCC and serum AFP >100 ng/mL.
  • Abandon or failure in first or second line treatment
  • Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
  • Child-Pugh score of A or B, Barcelona Clinic Liver Cancer stage of C or D
  • Life expectancy > 4 months
  • Karnofsky score ≥70%
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  • Adequate organ function as defined below:
  • Patients must have a serum Total bilirubin ≤2 x Upper Limit of Normal (ULN), Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤5 times the institutional ULN.
  • A pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute
  • Ejection fraction measured by echocardiogram or Multiple gated acquisition scanning (MUGA) >45% (evaluation done with 6 weeks of screening does not need to be repeated)
  • Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1)>45% predicted
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
  • Platelet count ≥ 50,000/mm3 (10^9/L)
  • 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 tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
  • Patients with an organ transplantation history
  • 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)
  • 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.
  • Women who are pregnant or breast-feed
  • HIV-infection

Trial locations and contacts

1 site in 1 country.

China1 site

  • The First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, 710061

Other trials in China

About this study

Official title: Phase 1, Open-label, Three Routes IV, Intratumoral Injections and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-ARTEMIS™2™ T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

Clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of ET1402L1-ARTEMIS™2 T cells in patients with alpha fetoprotein positive (AFP+ ) hepatocellular carcinoma (HCC).

Read the detailed description

The molecular target for ET1402L1-ARTEMIS™2 is human leukocyte antigen (HLA) -A02 complexed with a HLA-A02-restricted peptide of alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ARTEMIS™2 is a second generation ARTEMIS™ receptor engineered with a human antibody domain against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-ARTEMIS™2 T-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 intra-hepatic artery (IA) arm or Intratumoral Injections arm, with the ET1402L1-ARTEMIS™2 T-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the intravenous (IV) arm, with the ET1402L1-ARTEMIS™2 T-cells administered through intravenous infusion.

Being tested
ET1402L1-ARTEMIS™ T cells -IV, ET1402L1-ARTEMIS™ T cells -intra-hepatic artery, ET1402L1-ARTEMIS™ T cells -Intratumoral Injections
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.

  • ET1402L1-ARTEMIS™ T cells -IVBiological

    Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct -intravenous (i.v.) arm

  • ET1402L1-ARTEMIS™ T cells -intra-hepatic arteryBiological

    Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: intra-hepatic artery (i.a.) arm

  • ET1402L1-ARTEMIS™ T cells -Intratumoral InjectionsBiological

    Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: Intratumoral Injections (i.t.) arm

Study groups in NCT03888859
Study groupRoleWhat they receive
Intravenous (i.v.) armExperimentalautologous ET1402L1-ARTEMIS™2 T cells administered by intravenous (IV) infusion
Receives: Biological: ET1402L1-ARTEMIS™ T cells -IV
Intra-hepatic artery (i.a.) armExperimentalautologous ET1402L1-ARTEMIS™2 T cells administered by intra-hepatic artery (IA) infusion
Receives: Biological: ET1402L1-ARTEMIS™ T cells -intra-hepatic artery
Intratumoral Injections (i.t.) armExperimentalautologous ET1402L1-ARTEMIS™2 T cells administered by intratumoral injections (i.t.) infusion
Receives: Biological: ET1402L1-ARTEMIS™ T cells -Intratumoral Injections

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-ARTEMIS™2 T-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.

    Measured: 28 days up to 2 years

  2. Frequency of ARTEMIS T cell treatment-related adverse events

    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: Time Frame: 28 days up to 2 years

Secondary outcomes (12)

  1. Rate of disease response by RECIST in the liver

    Response rates will be estimated as the percent of patients with objective response (OR)，which was defined as any of complete remission (CR), partial response (PR) at 2 years.

    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)，which was defined as any of complete remission (CR), partial response (PR) at 2 years.

    Measured: 2 years

  3. Progression free survival (PFS)

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

    Measured: at 4 months, 1 year, 2 years

  4. Median Survival（MS）

    Median Survival（MS）at 4 months, 1 year and 2 years

    Measured: at 4 months, 1 year, 2 years

  5. Overall survival（OS）

    overall survival（OS）at 2 years

    Measured: at 2 years

  6. AFP serum levels

    Percent change compared to the baseline

    Measured: 2 years

  7. Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood

    Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level

    Measured: 2 years

  8. % of ET1402L1-ARTEMIS™2 T cells in peripheral blood

    %of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level

    Measured: 2 years

  9. AFP expression in tumors

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

    Measured: 4-8 weeks

  10. Tmax of serum Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor(TNF)-α and Interferon gamma (INFγ)

    Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for Tmax.

    Measured: 24 weeks

  11. AUC of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ

    Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for area under curve (AUC).

    Measured: 24 weeks

  12. Time to baseline for serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ

    Increase or decreases in the amount of IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing.

    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 posted25 Mar 2019
  2. Study start6 Dec 2017
  3. Primary completion13 Apr 2019
  4. Study completion8 Dec 2020

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
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03888859
Sponsor's protocol ID
XJTU1AF2017LSL-C002
Status last verified
Mar 2021
First submitted
1 Feb 2019
Last updated
29 Mar 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing ET1402L1-ARTEMIS™ T cells -IV, ET1402L1-ARTEMIS™ T cells -intra-hepatic artery and ET1402L1-ARTEMIS™ T cells -Intratumoral Injections in people with Hepatocellular Carcinoma and Liver Cancer, run by First Affiliated Hospital Xi'an Jiaotong 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 14 inclusion and 12 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 29 Mar 2021. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

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 NCT03888859.

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 29 Mar 2021.

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