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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03965546
• Other study ID #: 2019(ZD13)
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 30, 2019
• Est. completion date: June 2022

Study information

• Verified date: May 2019
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Yun Wang, PHD
• Phone: 86-18681869114
• Email: foolishyun[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: June 2022
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Cancer
• Liver Neoplasms
• Metastatic Liver Cancer

Intervention

Combination Product:
• Sorafenib combined with ET140202-T cell
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
• TAE combined with ET140202-T cell
Transarterial embolization(TAE) treatment Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) expression construct -intravenous (i.v.)

Biological:
• ET140202-T cell
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET140202) - expression construct -intravenous (i.v.)

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University	Eureka Therapeutics Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	28 days up to 2 years
Secondary	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.	2 years
Secondary	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).	2 years
Secondary	Progression free survival (PFS)	Progression free survival (PFS) at 4 months, 1 year and 2 years	at 4 months, 1 year, 2 years
Secondary	Median Survival(MS)	Median Survival(MS)at 4 months, 1 year and 2 years	at 4 months, 1 year, 2 years
Secondary	Overall survival(OS)	overall survival(OS)at 2 years	at 2 years
Secondary	AFP serum levels	Percent change compared to the baseline	2 years
Secondary	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	2 years
Secondary	Alpha-fetoprotein (AFP) expression in tumors	Percent of AFP-positive cells in randomly selected fields in tumor biopsies.	4-8 weeks
Secondary	IL-6 serum levels	Amount change compared to the baseline	4-8 weeks
Secondary	IL-2 serum levels	Amount change compared to the baseline	4-8 weeks
Secondary	IL-10 serum levels	Amount change compared to the baseline	4-8 weeks
Secondary	TNF-a serum levels	Amount change compared to the baseline	4-8 weeks
Secondary	IFN-? serum levels	Amount change compared to the baseline	4-8 weeks