Phase I Trial of Anti-GPC3 Chimeric T Cells for Subjects With GPC3-Positive Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and efficacy of anti-GPC3 scFv-41BB-CD3ζ-tEGFR chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating patients with GPC3-positive advanced hepatocellular carcinoma (HCC).
详细描述
Primary Objectives:
- To evaluate the safety of intravenous administration of the anti-GPC3 CAR-T cells in patients with HCC or lung squamous cell carcinoma
- To access the safety of anti-GPC3 CAR-T cells in HCC patients through catheter injection
Secondary Objectives:
- To evaluate the efficacy of anti-GPC3 CAR-T cells in patients with advanced HCC or lung squamous cell carcinoma
- To monitor the serum cytokine and expression level of tumor markers such as AFP, CEA and GPC3
- To assess the persistence in peripheral blood and intratumoral infiltration of anti-GPC3 CAR-T cells
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Expected to survive more than 3 months
- •Immunohistochemistry was confirmed to be GPC3 positive hepatocellular carcinoma
- •Patients with no ability to receive TACE combined with sorafenib
- •WBC>3.5×1e+9/L,Hb>90g/L,PLT>75×1e+9/L
- •HBV DNA copy number less than 100/ml
- •ALT≤5ULN, AST≤5ULN, TB≤1.5ULN, ALB≥35g/L
- •Understand this test and have signed informed consent
排除标准
- •Hepatic encephalopathy, autoimmune diseases, or any uncontrolled active disease that hinders participation in the trial
- •Decompensated liver cirrhosis, liver function Child-pugh C grade
- •Portal vein tumor thrombus, arterial portal fistula, hepatic arteriovenous
- •Long-term use of immunosuppressive agents after organ transplantation
- •Screening indicated that the target cell transfection rate was less than 30%
- •Invasive pulmonary embolism, deep venous thrombosis, or other major arterial / venous thromboembolic events occurred 30 days or 30 days prior to randomization
- •Subjects had an active or uncontrollable infection requiring systemic therapy 14 days or 14 days prior to randomization
- •Pregnant or lactating subjects
- •In the opinion of the investigator, the presence of a medical history or a history of mental state may increase the number of subjects associated with the risk factors associated with the study or study drug administration
- •Subjects who have signed a written consent or who are in compliance with the study procedure; or who are unwilling or unable to comply with the study
研究组 & 干预措施
anti-GPC3 CAR-T
Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
干预措施: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs (Biological)
anti-GPC3 CAR-T
Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
干预措施: Fludarabine (Drug)
anti-GPC3 CAR-T
Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
时间窗: 4 weeks
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
次要结局
- Persistence: Duration of CAR-positive T cells in circulation(6 months)
- Efficacy: Overall complete remission rate defined by the standard response criteria(8 weeks)
研究者
Qingzhu Jia, M.D.
Secretary of research
Xinqiao Hospital of Chongqing