Clinical trial NCT03965546: 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
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hepatocellular Carcinoma
Liver Cancer
Liver Neoplasms
Metastatic Liver Cancer
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Eureka Therapeutics Inc.
First posted: 2019-05-29
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Frequency of ARTEMIS T cell treatment-related adverse events
timeFrame: 28 days up to 2 years
Secondary outcomes:
measure: Rate of disease response by RECIST in the liver
timeFrame: 2 years
measure: Rate of disease response by RECIST at non-liver sites
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: at 4 months, 1 year, 2 years
measure: Median Survival（MS）
timeFrame: at 4 months, 1 year, 2 years
measure: Overall survival（OS）
timeFrame: at 2 years
measure: AFP serum levels
timeFrame: 2 years
measure: Number of ET140202-T cells in peripheral blood
timeFrame: 2 years
measure: Alpha-fetoprotein (AFP) expression in tumors
timeFrame: 4-8 weeks
measure: IL-6 serum levels
timeFrame: 4-8 weeks
measure: IL-2 serum levels
timeFrame: 4-8 weeks
measure: IL-10 serum levels
timeFrame: 4-8 weeks
measure: TNF-α serum levels
timeFrame: 4-8 weeks
measure: IFN-γ serum levels
timeFrame: 4-8 weeks
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Xue Hui, PHD
role: STUDY_CHAIR
References: