A Next-generation Sequencing Analysis to Investigate the Clinical Impact of Concomitant Genetic Alterations in the Patients With Advanced EGFR-mutated Lung Adenocarcinoma: A Multicenter Study.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Change of mutation profiles between pre/post TKI treatment
研究概览
简要总结
The concomitant co-mutation with epidermal growth factor receptor (EGFR) mutation might influence the clinical outcomes. The investigators will identify the impact of concommitant mutation on clinical outcome in patients with advanced -EGFR mutated adenocarcinoma.
The investigators will compare the genetic alterations between tumors of pre and post Tyrosin Kinase Inhibitor(TKI) treatments and predict the resistance mechanism for EGFR-TKIs by next-generation sequencing(NGS) analysis.
详细描述
The current standard therapies in the treatment of advanced EGFR-mutated lung cancer patients are the 1st or 2nd EGFR-TKIs. Although 70-80% of patients treated by EGFR-TKIS show good responses, they have progression after around 12 months. The concomitant co-mutation with EGFR mutation might influence the drug response of EGFR TKI. The investigators will compare the progression-free survival (PFS) of EGFR-TKI according to co-occuring mutations.
The patients experience the change of molecular profiles after using the TKI. Therefore, the investigators will investigate the molecular profiles through NGS panel with foundation medicine in the tissue of pre/post EGFR-TKI, compare the change of the molecular profiles and tumor mutation burden(TMB), and identify novel mechanisms of drug resistance.
The investigators will collect the tumor tissues and blood of around 80 patients in multi-centers prospectively. Then, They will be sent to FoundationOne in the US and perform NGS analysis. The type of EGFR-TKIs would be selected according to physicians' preference. NGS will be performed twice before the EGFR-TKIs treatment and after the progression.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form
- •Age ≥19 years
- •EGFR-mutated stage IV lung adenocarcinoma patients
- •Archival biopsy tissues which are from core needle biopsies, endobronchial ultrasound (EBUS) guided- lymph node biopsy or lymph node excisional biopsy at baseline and at radiologic progression
- •Availability of the 10 unstained slides and 1 H&E slides at pre/ post TKI treatment
- •Samples should contain a minimum of 20% viable tumor cells that preserve
排除标准
- •Tumor tissue from bone metastases that have been decalcified are not acceptable.
结局指标
主要结局
Change of mutation profiles between pre/post TKI treatment
时间窗: through study completion, an average of 1 year
Comparison of the kinds of the mutation between pre- and post TKI treatment
次要结局
- The number and the kinds of co-occurring mutations on tumors before and after TKI treatment(through study completion, an average of 1 year)
- Tumor mutation burden in tumors tissues before and after TKI treatment(through study completion, an average of 1 year)
- PFS according to the co-occurring mutations with pre-TKI treatment(through study completion, an average of 1 year)
- The correlation between the change of variant allele frequency(VAF) and drug response in matched tumors tissues before and after TKI treatment(through study completion, an average of 1 year)
- The concordance the the mutation profiles in the NGS results of tissue and blood in the same patients(through study completion, an average of 1 year)
研究者
Kye Young Lee
Professor
Konkuk University Medical Center