search
Back to results

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

Primary Purpose

Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasms

Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Sorafenib combined with ET140202-T cell
TAE combined with ET140202-T cell
ET140202-T cell
Sponsored by
First Affiliated Hospital Xi'an Jiaotong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

ET140202-T cell combine with Sorafenib

ET140202-T cell combine with TAE

solo ET140202-T cell

Arm Description

Sorafenib treatment everyday and autologous ET140202-T cell administered by intravenous (IV) infusion

TAE treatment ahead every two times of autologous ET140202-T cell administered by intravenous (IV) infusion

autologous ET140202-T cell administered by intravenous (IV) infusion

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
May 24, 2019
Last Updated
August 6, 2019
Sponsor
First Affiliated Hospital Xi'an Jiaotong University
Collaborators
Eureka Therapeutics Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03965546
Brief Title
ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Liver Cancer
Official Title
Clinical Study of ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Advanced Liver Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 30, 2019 (Actual)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
June 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First Affiliated Hospital Xi'an Jiaotong University
Collaborators
Eureka Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasms, Metastatic Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ET140202-T cell combine with Sorafenib
Arm Type
Experimental
Arm Description
Sorafenib treatment everyday and autologous ET140202-T cell administered by intravenous (IV) infusion
Arm Title
ET140202-T cell combine with TAE
Arm Type
Experimental
Arm Description
TAE treatment ahead every two times of autologous ET140202-T cell administered by intravenous (IV) infusion
Arm Title
solo ET140202-T cell
Arm Type
Experimental
Arm Description
autologous ET140202-T cell administered by intravenous (IV) infusion
Intervention Type
Combination Product
Intervention Name(s)
Sorafenib combined with ET140202-T cell
Intervention Description
Sorafenib starting dose of 400mg b.i.d. a.c. Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct by intravenous (IV) infusion
Intervention Type
Combination Product
Intervention Name(s)
TAE combined with ET140202-T cell
Intervention Description
Transarterial embolization(TAE) treatment Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct -intravenous (i.v.)
Intervention Type
Biological
Intervention Name(s)
ET140202-T cell
Intervention Description
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) - expression construct -intravenous (i.v.)
Primary Outcome Measure Information:
Title
Frequency of ARTEMIS T cell treatment-related adverse events
Description
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.
Time Frame
28 days up to 2 years
Secondary Outcome Measure Information:
Title
Rate of disease response by RECIST in the liver
Description
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.
Time Frame
2 years
Title
Rate of disease response by RECIST at non-liver sites
Description
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).
Time Frame
2 years
Title
Progression free survival (PFS)
Description
Progression free survival (PFS) at 4 months, 1 year and 2 years
Time Frame
at 4 months, 1 year, 2 years
Title
Median Survival（MS）
Description
Median Survival（MS）at 4 months, 1 year and 2 years
Time Frame
at 4 months, 1 year, 2 years
Title
Overall survival（OS）
Description
overall survival（OS）at 2 years
Time Frame
at 2 years
Title
AFP serum levels
Description
Percent change compared to the baseline
Time Frame
2 years
Title
Number of ET140202-T cells in peripheral blood
Description
Number of ET140202-T cells in peripheral blood will be presented as Time to peak, Time to baseline level
Time Frame
2 years
Title
Alpha-fetoprotein (AFP) expression in tumors
Description
Percent of AFP-positive cells in randomly selected fields in tumor biopsies.
Time Frame
4-8 weeks
Title
IL-6 serum levels
Description
Amount change compared to the baseline
Time Frame
4-8 weeks
Title
IL-2 serum levels
Description
Amount change compared to the baseline
Time Frame
4-8 weeks
Title
IL-10 serum levels
Description
Amount change compared to the baseline
Time Frame
4-8 weeks
Title
TNF-α serum levels
Description
Amount change compared to the baseline
Time Frame
4-8 weeks
Title
IFN-γ serum levels
Description
Amount change compared to the baseline
Time Frame
4-8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute. Patients must have a serum direct bilirubin ≤3 x ULN, ALT and AST ≤5 x ULN. Ejection Fraction measured by echocardiogram or MUGA >50% (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) INR ≤1.5 x ULN 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yun Wang, PHD
Phone
86-18681869114
Email
foolishyun@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xue Hui, PHD
Organizational Affiliation
First Affiliated Hospital of Xian Jiaotong University
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710061
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yun Wang
Phone
86-18681869114
Email
foolishyun@126.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs