Retrospective Study Based on Pharmacokinetics, Somatic Mutations and Genetic Polymorphisms Related to Individual Variations of Drug Effect and Adverse Drug Reaction of Imatinib in Gastrointestinal Stromal Tumor Treatment.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
For patients of GIST (Gastrointestinal Stromal Tumor), Imatinib has been widely used in GIST with KIT or PDGFRA sensitive mutations. From clinical points of view, individual differences often occur between different patients, leading diverse effect in ADR and drug effect. Meanwhile, the drug effect and adverse drug reaction was significantly influenced by the pharmacokinetic factors and pharmacodynamic and other factors. In this research, we try to establish a more sensitive method to detect sensitive mutations in plasma and discover the correlation between somatic and germline mutations, plasma trough concentration and drug effect, the association between ADME-associated SNP, Target/Receptor/Pathway-associated SNP, trough concentration and TKI adverse effect. Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.
详细描述
The plasma concentration of Imatinib were established. The ADME-associated SNPs included are CYP3A4, CYP3A4, CYP1A1, CYP2C9, CYP2C19, ABCB1, ABCG2, ABCC4, SLC22A1, SLCO1B3 and so on. The Target/Receptor/Pathway-associated SNP s included KIT, PDGFRA, PDGFRB, FLT1, FLT3, MAPK1, SHC1, CCL5, CXCL14 and so on. The somatic mutations included are KIT, PDGFRA, BRAF and so on.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main patient entry criteria included: age≥ 18 years; histologically and cytologically proved GIST; Eastern cooperative oncology group performance status (ECOGPS)≤2; adequate hematological,renal,and hepatic functions.
排除标准
- •uncontrolled systemic disease,and other chemotherapy at the time of inclusion. The protocol was approved by the Ethical Committee of Cancer Center of Sun Yat-Sen University (CCSU), and written informed consent was obtained form each patient.
结局指标
主要结局
Progression free survival
时间窗: The time from the date of randomisation (baseline) to the date of objective tumour progression，and expected average of 36 months.
Excluding clinical deterioration without evidence of objective progression according to the Response Evaluation Criteria In Solid Tumors (RECIST), or death from any cause.
次要结局
- Number of patients with objective response and adverse events(one month, three month, 12 month)
研究者
Xueding Wang
Institute of Clinical Pharmacology
Sun Yat-sen University