To Investigate the Efficacy and Resistance Mechanisms of Intrathecal Pemetrexed in Advanced Non-small Cell Lung Cancer (NSCLC) Patients Harboring Oncogenic Mutations With Leptomeningeal Metastases
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Intracranial progression-free survival (I-PFS)
研究概览
简要总结
This is a prospective interventional study clinical study to investigate the efficacy and resistance mechanisms of intrathecal pemetrexed in patients with driver gene mutations advanced NSCLC with leptomeningeal metastases.
详细描述
This is a prospective interventional clinical study aimed at investigating the efficacy and resistance mechanisms of intrathecal pemetrexed in advanced NSCLC patients with EGFR, ALK, and ROS1 mutations presenting leptomeningeal metastases. Approximately 30 advanced NSCLC patients with EGFR, ALK, and ROS1 mutations, who have developed leptomeningeal metastases following TKI resistance, will receive intrathecal pemetrexed. Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms and differences. Second-generation gene detection will be performed to identify potential resistance mechanisms to pemetrexed. The study is expected to commence recruitment in mainland China around April 2024, with an anticipated completion date in April 2025.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Histopathology or cytology confirmed metastatic non-small cell lung cancer with leptomeningeal metastasis after TKI resistant.
- •EGFR mutant, ALK fusion, ROS1 fusion, and other oncogenic alterations including RET fusion, BRAF mutation, NTRK fusion, KRAS mutation was confirmed by an accredited local laboratory.
- •Adequate bone marrow hematopoiesis and organ function
- •Agree to receive intrathecal pemetrexed
- •Predicted survival ≥ 12 weeks.
排除标准
- •Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
- •Subjects who have received any of the following treatments must be excluded:
- •Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
- •Presence of spinal cord compression or meningeal metastasis.
- •History of other malignant tumors within 2 years.
- •Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
- •History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
- •The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
- •Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
- •Heart-related diseases or abnormalities
- •Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
- •Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
- •Live vaccine was given 2 weeks before the first medication.
- •Women who are breastfeeding or pregnant.
- •Hypersensitivity to the test drug and the ingredients.
- •Other conditions assessed by the investigator to be unsuitable for participation in the study.
研究组 & 干预措施
Intrathecal pemetrexed
Intrathecal pemetrexed
干预措施: Intrathecal pemetrexed (Drug)
结局指标
主要结局
Intracranial progression-free survival (I-PFS)
时间窗: Time from first subject dose to study completion, or up to 36 month
Intracranial progression-free survival was defined as the duration from the start of IP to the worsening of neurological symptoms, radiological confirmation of brain progression, or patient death
次要结局
- System progression-free survival (s-PFS)(Time from first subject dose to study completion, or up to 36 month)
研究者
Yongchang Zhang
professor
Hunan Province Tumor Hospital