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

Early Phase 1

• Conditions: Hepatocellular Carcinoma; Liver Neoplasms; Liver Cancer; Metastatic Liver Cancer

• Registration Number: NCT03965546
• Lead Sponsor: First Affiliated Hospital Xi'an Jiaotong University

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.

Study Timeline

• Status Verified: 2019-05
• Study First Submitted: 2019-05-24
• Study First Submitted QC: 2019-05-24
• Study First Posted: 2019-05-29
• Study Start: 2019-05-30
• Last Update Submitted: 2019-08-06
• Last Update Posted: 2019-08-08
• Primary Completion: 2021-06
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 27

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Frequency of ARTEMIS T cell treatment-related adverse events	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shaanxi, China