Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasms, Metastatic Liver Cancer
Conditions
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.
Interventions
COMBINATION_PRODUCTSorafenib combined with ET140202-T cell
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
COMBINATION_PRODUCTTAE combined with ET140202-T cell
1. Transarterial embolization(TAE) treatment 2. Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct -intravenous (i.v.)
BIOLOGICALET140202-T cell
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) - expression construct -intravenous (i.v.)
Sponsors
Eureka Therapeutics Inc.
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Progression free survival (PFS) | at 4 months, 1 year, 2 years | Progression free survival (PFS) at 4 months, 1 year and 2 years |
| Median Survival（MS） | at 4 months, 1 year, 2 years | Median Survival（MS）at 4 months, 1 year and 2 years |
| Overall survival（OS） | at 2 years | overall survival（OS）at 2 years |
| AFP serum levels | 2 years | Percent change compared to the baseline |
| 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 |
| 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. |
| IL-6 serum levels | 4-8 weeks | Amount change compared to the baseline |
| 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 |
| 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 |
| Alpha-fetoprotein (AFP) expression in tumors | 4-8 weeks | Percent of AFP-positive cells in randomly selected fields in tumor biopsies. |
Countries
China
Contacts
Primary ContactYun Wang, PHD
Outcome results
None listed