A Clinical Trial of Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Clinical response rate
研究概览
简要总结
Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in the treatment of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. Due to its small molecule properties, it can effectively penetrate the central nervous system barrier and deliver an effective antitumor effect. An international multi-center clinical study published in 2019 confirmed that double-dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R/T790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, whether third-generation small molecule TKI drugs (e.g. 'osimertinib') combined with intrathecal pemetrexed could benefit patients with LM from EGFR- mutant NSCLC remains undetermined.
详细描述
The aim of this Study is to compare the effects of intra-pemetrexed Plus third-generation small molecule TKI drugs (e.g. 'osimertinib') versus third-generation small molecule TKI drugs alone in leptomeningeal metastasis from EGFR mutation positive NSCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Male or female aged between 18 and 75 years.
- •Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).
- •Confirmed diagnosis of leptomeningeal metastasis according to ESMO/EANO guidelines.
- •Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm
- •No history of severe nervous system disease.
- •No severe dyscrasia.
排除标准
- •Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than
- •Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
- •Patients with poor compliance or other reasons that were unsuitable for this study.
研究组 & 干预措施
Group A
Intra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib')
干预措施: Osimertinib (Drug)
Group A
Intra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib')
干预措施: Pemetrexed (Drug)
Group B
Third-generation small molecule TKI drugs (e.g. 'osimertinib') alone
干预措施: Osimertinib (Drug)
结局指标
主要结局
Clinical response rate
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
次要结局
- Overall survival(From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).)
- Incidence of treatment-related adverse events(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.)
研究者
Zhenyu Pan
Professor
Guangzhou Medical University