ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Liver Cancer

Clinical Study of ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Advanced Liver Cancer

The purpose of this study is to evaluate the efficacy and safety of ET 140202 -T cell combined With TAE or Sorafenib in the treatment of liver cancer

Study Overview

Detailed Description

The molecular target for ET140202-T cells is HLA-A02 complexed with a HLA-A02-restricted peptide of alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). This clinical study evaluates the safety and pharmacokinetics of ET140202-T cells with TAE or Sorafenib in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Study Type

Interventional

Enrollment (Anticipated)

27

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • Recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • AFP-expressing HCC and serum AFP >10 x ULN
  • 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, ECOG 0-2, Life expectancy > 6 months
  • Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured.
  • Negative serum pregnancy test for women with childbearing potential
  • Adequate organ function as defined below:

    1. A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute.
    2. Patients must have a serum direct bilirubin ≤3 x ULN, ALT and AST ≤5 x ULN.
    3. Ejection Fraction measured by echocardiogram or MUGA >50% (evaluation done within 6 weeks of screening does not need to be repeated)
    4. DLCO or FEV1 >45% predicted
    5. Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L), Platelet count ≥ 50,000/mm3 (10^9/L)
    6. INR ≤1.5 x ULN
    7. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ET140202-T cell combine with Sorafenib
Sorafenib treatment everyday and autologous ET140202-T cell administered by intravenous (IV) infusion
  1. Sorafenib starting dose of 400mg b.i.d. a.c.
  2. Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct by intravenous (IV) infusion
EXPERIMENTAL: ET140202-T cell combine with TAE
TAE treatment ahead every two times of autologous ET140202-T cell administered by intravenous (IV) infusion
  1. Transarterial embolization(TAE) treatment
  2. Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct -intravenous (i.v.)
EXPERIMENTAL: solo ET140202-T cell
autologous ET140202-T cell administered by intravenous (IV) infusion
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) - expression construct -intravenous (i.v.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of ARTEMIS T cell treatment-related adverse events
Time Frame: 28 days up to 2 years
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.
28 days up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of disease response by RECIST at non-liver sites
Time Frame: 2 years
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).
2 years
AFP serum levels
Time Frame: 2 years
Percent change compared to the baseline
2 years
Rate of disease response by RECIST in the liver
Time Frame: 2 years
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.
2 years
Progression free survival (PFS)
Time Frame: at 4 months, 1 year, 2 years
Progression free survival (PFS) at 4 months, 1 year and 2 years
at 4 months, 1 year, 2 years
Median Survival(MS)
Time Frame: at 4 months, 1 year, 2 years
Median Survival(MS)at 4 months, 1 year and 2 years
at 4 months, 1 year, 2 years
Overall survival(OS)
Time Frame: at 2 years
overall survival(OS)at 2 years
at 2 years
Number of ET140202-T cells in peripheral blood
Time Frame: 2 years
Number of ET140202-T cells in peripheral blood will be presented as Time to peak, Time to baseline level
2 years
Alpha-fetoprotein (AFP) expression in tumors
Time Frame: 4-8 weeks
Percent of AFP-positive cells in randomly selected fields in tumor biopsies.
4-8 weeks
IL-6 serum levels
Time Frame: 4-8 weeks
Amount change compared to the baseline
4-8 weeks
IL-2 serum levels
Time Frame: 4-8 weeks
Amount change compared to the baseline
4-8 weeks
IL-10 serum levels
Time Frame: 4-8 weeks
Amount change compared to the baseline
4-8 weeks
TNF-α serum levels
Time Frame: 4-8 weeks
Amount change compared to the baseline
4-8 weeks
IFN-γ serum levels
Time Frame: 4-8 weeks
Amount change compared to the baseline
4-8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Chair: Xue Hui, PHD, First Affiliated Hospital of Xian Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 30, 2019

Primary Completion (ANTICIPATED)

June 1, 2021

Study Completion (ANTICIPATED)

June 1, 2022

Study Registration Dates

First Submitted

May 24, 2019

First Submitted That Met QC Criteria

May 24, 2019

First Posted (ACTUAL)

May 29, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 8, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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