NCT04756648进行中（未招募）1 期
An Open, Dose Escalation/Dose Exploration, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single/Multiple Infusion of CT0180 Injection in Patients With Advanced Hepatocellular Carcinoma
Zhejiang University1 个研究点 分布在 1 个国家目标入组 21 人开始时间: 2021年3月10日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Dose-Limiting Toxicity（DLT）
研究概览
简要总结
A Phase I Clinical Study ofCT0180 cells in Patients with Advanced Hepatocellular Carcinoma
详细描述
Primary objectives:
Evaluate the safety and tolerance of CT0180 cells in patients with advanced hepatocellular carcinoma within 28 days after the first infusion
Secondary objectives:
- Evaluate the metabolic kinetics of CT0180 cells ; · Evaluate overall safety and tolerability ; · Evaluate the initial efficacy of CT0180 cell infusion in the treatment of advanced hepatocellular carcinoma with positive Glypican-3（GPC3 ）expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years, either sex；
- •Patients with clinically or pathologically confirmed hepatocellular carcinoma were treated with surgery or local treatment It is not suitable for surgery or local radical treatment;
- •Progression or intolerance after at least one previous systemic treatment, or due to specific reasons unable to receive systemic treatment. Systemic therapy can include: Programmed Death 1（PD-1） / programmed cell death-Ligand 1（PD-L1） monoclonal antibody Antibodies, molecular targeted drugs (e.g. sorafenib, regofinib, renvastinib)and conventional chemotherapy, etc;
- •According to Barcelona Clinic Liver Cancer（BCLC）, the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
- •In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
- •According to Response Evaluation Criteria in SolidTumors（RECIST1.1）,patients have at least one evaluable target lesion, defined as: the longest diameter of non-lymph node lesion ≥ 10 mm, or the shortest diameter of lymph node lesion ≥ 15 mm); hepatic lesions require arterial phase contrast enhancement;
- •Expected survival is > 12 weeks;
- •Cirrhosis status Child-Pugh score: Grade A;
- •Eastern Cooperative Oncology Group（ ECOG） Performance Status score: 0 to 1 point;
- •If the patient is HBsAg positive or HBcAb positive, HBV-DNA should be <2000 IU/ml. HBsAg positive patients must receive antiviral treatment ;
- •Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment and adequate liver, renal, cardiovascular, respiratory function;
- •Have venous accesses for apheresis;
- •Subjects of childbearing age must undergo a serum pregnancy test within 14 days before the initiation of the study and the result must be negative. In addition, they should be willing to use a reliable method of contraception during the trial (within 52 weeks after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial;
- •Understand and sign informed consent.
排除标准
- •Pregnant or breast-feeding women;
- •Hepatitis virus C antibodies ,human immunodeficiency virus（HIV） antibodies or Syphilis Serological tests are positive;
- •Any uncontrol active infection, including but not limited to active tuberculosis;
- •Have clinically significant thyroid dysfunction except the stable control after treatment;
- •Previous or present hepatic encephalopathy;
- •Current clinically significant ascites;
- •Imaging results:≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or metastases to the central nervous system, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
- •Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
- •The side effects caused by the previous treatment of the subjects did not return to Common Terminology Criteria for Adverse Events（CTCAE） ≤1; except hair loss and other tolerable events determined by investigator;
- •Patients who had received systemic steroids or other immunosuppressive agents within 7 days before apheresis, except inhaled steroids;
- •History of severe allergy ,allergic to CT0180 cell fluid adjuvant such as Dimethyl sulfoxide（DMSO）;
- •Has signs of central nervous system disease or an abnormal neurological examination with clinical significance;
- •Subjects with unstable or active ulcers, gastrointestinal bleeding, or pump inhibitor intolerance;
- •Patients with a history of organ transplantation or waiting for organ transplantation;
- •Previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks or local treatment and systemic chemotheray within 2 weeks or immunotheray and molecular targeted drugs within 1 week before apheresis;
- •Previously received GPC3 targeted therapy;
- •Major surgery or significant trauma occurred within 4 weeks before apheresis, or it is expected that major surgery needs to be performed during the trial;
- •Patients who had incurable malignant tumors in the past 5 years or at the same time, except cervical cancer in situ and basal cell carcinoma of skin;
- •Other serious diseases that may restrict the subjects from participating in the trial ；
- •The researcher assessed that the subjects were unable or unwilling to comply with the requirements of the trial protocol.
研究组 & 干预措施
CT0180 cells
Experimental
CT0180 Cells infusion after lymphocyte-depleting with fludarabine and cyclophosphamide.
干预措施: CT0180 Cells (Drug)
结局指标
主要结局
Dose-Limiting Toxicity（DLT）
时间窗: 28 days
Safety
Maximal Tolerable Dose（MTD）
时间窗: 28 days
tolerability evaluation
Adverse Event（AE）
时间窗: 28 days
Incidence rate
Adverse Event of Special Interest （ AESI）
时间窗: 28 days
Incidence rate
次要结局
- Number of cells(52 weeks)
- Antitumor efficacy-Duration of disease control (DDC)(52 weeks)
- Treatment Emergent Adverse Event(TEAE)(52 weeks)
- Antitumor efficacy-Objective response rate (ORR)(52 weeks)
- Antitumor efficacy-Overall survival (OS)(52 weeks)
- Antitumor efficacy-Disease control rate (DCR)(52 weeks)
- Antitumor efficacy-Duration of response (DOR)(52 weeks)
- Antitumor efficacy-Progression-free survival (PFS)(52 weeks)
研究者
TingBo Liang
Professor
Zhejiang University
研究点 (1)
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