Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of GST-HG161
Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of the Selective c-MET Inhibitor GST-HG161 in Patients With Advanced or Metastatic Solid Tumors
研究概览
详细说明
This is a phase I trial to evaluate safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy GST-HG161.
There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort. Recommended protocal in the dose expansion stage will be determined by the results in the dose escalation stage .
研究类型
注册 (预期的)
阶段
- 阶段1
联系人和位置
学习地点
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Shanghai
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Shanghai、Shanghai、中国、200135
- 招聘中
- Shanghai Oriental Hospital
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接触:
- JI LI, Professor
- 电话号码:+86 021-38804518
- 邮箱:lijin@csco.org.cn
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Voluntarily participate in this study and sign the informed consent;
- Aged >=18 years;
- Patients with advanced or metastatic solid tumors diagnosed histologically or cytologically, and no approved standard treatment regimen or no efficacy or intolerance to standard treatment regimen;
- Patients with solid tumors confirmed c-Met positive by testing. The definition of c-Met positive is: 1) IHC expression of c-Met (positive criteria : 1+ and above); 2) FISH amplification of c-Met (positive criteria: Ratio>=1.8), any positive of the above two methods can be enrolled into the group;
- The investigators evaluate according to RECIST v1.1, subjects must have at least one evaluable focus;
- Performance status 0 or 1 based on ECOG scale;
Adequate bone marrow and major organ functions:
Bone marrow: Hemoglobin>=9.0 g/dL, absolute count of neutrophils>1.5x10^9/L, platelet≥75x10^9/L; Coagulation function: Prothrombin time (PT)<=1.5 ULN, international normalized ratio (INR)<=1.5 ULN; Hepatic function: Total bilirubin<=1.5 ULN, ALT<=2.5 ULN, AST<=2.5 ULN; For patients with hepatic metastases or hepatoma, total bilirubin<=2 ULN, ALT<=5 ULN, AST<=5 ULN are allowed; Renal function: Serum creatinine<1.5 ULN, creatinine clearance rate>50mL/min; Other laboratory inspection indexes: Lipase 1.5 ULN, amylase<1.5 ULN, albumin>=28g/L;
- Expected survival time>=12 weeks;
- Fertile men and women must agree to carry out birth control with effective methods for a period of 180 days from the signing of the informed consent form until the last administration of investigational drug. Fertile women include premenopausal women and women 2 years before menopause. Fertile women must have a negative pregnancy test within 7 days (including) before the first dose of the investigational drug;
- Subjects or their legal representatives are able to communicate well with the investigators and complete the study in accordance with protocol.
Exclusion Criteria:
- Patients with clinical symptoms of brain metastasis, spinal cord compression, carcinomatous meningitis, or other evidence showing that the brain or spinal cord metastasis has not been controlled, and patients not suitable for the group judged by the investigators;
- Obvious basic cardiovascular diseases, including the following conditions: Prolonged QT/QTcF interval in baseline ECG (QTcF >480ms); Severe abnormalities in baseline ECG, including rhythm, conduction, and form. For example, complete left bundle branch block, degree III atrioventricular block, etc.; Cardiovascular abnormalities identified within 6 months, such as myocardial infraction, arrhythmia, angina, angioplasty, stent implantation, coronary artery bridging, congestive heart failure, etc.; Left ventricular ejection fraction is lower than the minimum normal value showed by cardiac ultrasound; Uncontrolled hypotension or uncontrolled hypertension;
- Digestive tract disorder that affect clinical trials, such as: Intractable hiccups, nausea, emesis, etc.; Chronic digestive diseases: Crohn's disease, ulcerative colitis, etc.; Dysphagia;
- Patients with a history of other serious underlying diseases, such as: A definite history of neurological or psychiatric disorders, including epilepsy or dementia; Patients with active hepatitis B (HBV-DNA>1000 copy number/mL), or hepatitis C virus antibody or HCV-RNA positive, or infected with human immunodeficiency virus (HIV); A history of organ transplantation; Severe infection;
- Pregnant or lactating women;
- Received chemotherapy, radiation therapy, hormonal therapy, biological therapy or other anti-tumor treatment within 4 weeks (from the last medication of mitomycin and nitrosoureas for at least 6 weeks, from the last medication of fluorouracil oral drugs, such as Tegafur, Capecitabine for at least 2 weeks), or the treatment is still within 5 half-life period;
- The adverse reactions of previous anti-tumor treatments have not recovered to CTCAE 5.0 level<=1 (except for hair loss);
- Participated in other clinical trials as a subject within 4 weeks prior to this study;
- The investigators determine ineligible to participate in the clinical trial for other reasons.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:GST-HG161
There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort.
Recommended dose in the dose expansion stage will be determined by the results in the dose escalation stage .
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There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort.
Recommended dose in the dose expansion stage will be determined by the results in the dose escalation stage .
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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DLT (Dose-Limiting Toxicity)
大体时间:Up to 27 days
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DLT was defined as one of the following adverse events (AEs) observed in 27 days: Grade 4 hematologic AE; Grade >=3 febrile neutropenia; Grade 3 thrombocytopenia with bleeding; Grade >=3 nausea, emesis, diarrhea and constipation, despite optimal treatment; Grade >=3 non-hematological AE.
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Up to 27 days
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MTD (Maximum Tolerated Dose)
大体时间:Up to 27 days
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MTD was defined as the dose level at which 1 out of 6 subjects or no one experienced a DLT.
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Up to 27 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Area Under Curve (AUC)
大体时间:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Peak Plasma Concentration (Cmax)
大体时间:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Cl/F
大体时间:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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T1/2
大体时间:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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ORR
大体时间:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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Objective response rate (ORR) is defined as the proportion of subjects with complete or partial response as determined by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
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From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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PFS
大体时间:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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PFS(Progression-Free-Survival) was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever came first.
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From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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合作者和调查者
调查人员
- 首席研究员:JI LI, PHD、Shanghai Oriental Hospital ,China
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- GST-HG161-I
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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实体瘤的临床试验
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AstraZeneca招聘中Adv Solid Malig - H&N SCC、ATM Pro / Def NSCLC、胃癌、乳腺癌和卵巢癌西班牙, 美国, 比利时, 英国, 法国, 匈牙利, 加拿大, 大韩民国, 澳大利亚
GST-HG161的临床试验
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Fujian Akeylink Biotechnology Co., Ltd.招聘中
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Baylor College of MedicineGeorge Washington University; Children's National Research Institute完全的
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Fujian Akeylink Biotechnology Co., Ltd.The First Hospital of Jilin University招聘中