A Phase II, Open-label, Study in Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy
试验速览
- 阶段
- 2 期
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Response rate
研究概览
简要总结
KIT is a receptor tyrosine kinase that binds to stem-cell factor (SCF), activating a series of downstream effector pathways. KIT is an established therapeutic target in cancer with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and significant benefit is achieved with various small molecule inhibitors of KIT such as imatinib mesylate. Moreover, there is increasing evidence implicating KIT mutations as tractable therapeutic targets in melanoma. Additional information is required to characterize the functional role of low-frequency mutations in KIT and to determine whether amplification of wild type KIT is a real driver that can be targeted therapeutically. Except GIST and melanoma, other solid cancers were reported to have KIT mutation even in low frequency. A molecular profiling of the tumors of patients referred to the phase I clinic at the M.D. Anderson Cancer Center showed KIT mutation in 7 patients in total of 431 patients (2%).
Hence, the investigators planned this study to apply the molecularly targeted agent, imatinib to various types of cancers harboring KIT mutation or amplification.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •advanced, refractory cancer patients who failed standard of care (SOC)
- •KIT aberration: defined as mutation in exons 9, 11, 13, 17 or 18, or nanostring CNV by quantitative PCR (greater than 3 copies) or subject with specific sensitivity (Z-score<-1) to imatinib by Avatar scan whose disease has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy
- •ECOG performance status of 0~2
- •measurable or evaluable lesion per RECIST 1.1 criteria
- •adequate marrow, hepatic, renal and cardiac functions
- •Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
- •Total serum bilirubin ≤ 1.5 x ULN
- •Absolute neutrophil count(ANC) ≥ 1,500/uL
- •Platelets ≥ 100,0000/uL
- •Hemoglobin ≥ 9.0 g/dL
- •provision of a signed written informed consent
排除标准
- •severe co-morbid illness and/or active infections
- •pregnant or lactating women
- •history of major surgery or radiotherapy within 4 weeks
- •active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
- •known history of hypersensitivity to study drugs
研究组 & 干预措施
Imatinib
Imatinib 400mg qd daily Until disease progression, patient's refusal
干预措施: Imatinib (Drug)
结局指标
主要结局
Response rate
时间窗: expected average of 24 weeks
Response will be evaluated according to RECIST(Response Evaluation Criteria In Solid Tumors) 1.1 guidelines.Tumor responses will be assessed after the 2cycle chemotherapy and after completion of treatment. They should be classified as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) according to the Revised Response Criteria for refractory, metastatic cancer harboring KIT mutation or amplification.
次要结局
- Progression-free survival(expected average of 24 weeks)
- Duration of response(expected average of 24 weeks)
- Overall survival(expected average of 3years)
- Number of subjects with Adverse Events as a measure of safety(expected average of 24 weeks)
研究者
Jeeyun Lee
MD,PhD
Samsung Medical Center