Hepatocellular Carcinoma Clinical Trial
Official title:
Phase 1, Open-label, Two Routes IV and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-CAR T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)
Verified date | June 2019 |
Source | Aeon Therapeutics (Shanghai) Co., Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC
Status | Terminated |
Enrollment | 3 |
Est. completion date | January 10, 2019 |
Est. primary completion date | January 10, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - AFP-expressing HCC and serum AFP >100 ng/mL. - Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is = 20 mm. - Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele - Child-Pugh score of A or B - Life expectancy > 4 months - Age at time of enrollment is =18 years of age. - KPS =70% - Adequate organ function as defined below: - A pretreatment measured creatinine clearance (absolute value) of =50 ml/minute. - Patients must have a serum direct bilirubin =2 x ULN, ALT and AST =5 times the institutional upper limits of normal. - Ejection Fraction measured by echocardiogram or MUGA >45% (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) - Negative serum pregnancy test for women with childbearing potential - 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 an organ transplantation history - Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver. - 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) - Patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.). - 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. - HIV-infection - Women who are pregnant |
Country | Name | City | State |
---|---|---|---|
China | Renmin Hospital of Wuhan University | Wuhan | Hubei |
Lead Sponsor | Collaborator |
---|---|
Aeon Therapeutics (Shanghai) Co., Ltd. | Eureka Therapeutics Inc., Renmin Hospital of Wuhan University |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of patients with dose-limiting toxicity | A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET1402L1-CART-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits. | 28 days up to 2 years | |
Primary | Toxicity profile of ET1402L1-CART-cell treatment | Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET1402L1-CART T cells related toxicity. 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), complete remission (CR), partial response (PR), stable disease (SD), no response (NR), overall survival (OS). | 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 | Anti-tumor responses | Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years | 4 months, 1 year, 2 years | |
Secondary | AFP serum levels | Percent change compared to the baseline | 2 years | |
Secondary | CART cell engraftment | Number and % of ET1402L1-CART cells in peripheral blood will be presented as Time to peak, Time to baseline level and the overall exposure will be presented as area under curve (AUC). | 2 years | |
Secondary | AFP expression in tumors | Percent of AFP-positive cells in randomly selected fields in tumor biopsies | 4-8 weeks | |
Secondary | Tmax of serum cytokine levels | Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as time to peak level. | 24 weeks | |
Secondary | Time to baseline for serum cytokine levels | Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as Time to baseline. | 24 weeks | |
Secondary | AUC of serum cytokine levels | Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as area under curve (AUC). | 24 weeks |
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