The Efficacy and Safety of Intrathecal Pemetrexed for SCLC Patients With Refractory Brain Metastases or Leptomeningeal Metastasis: A Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis.
详细描述
This is a prospective interventional clinical study to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis. Approximately 80 small cell lung cancer patients with refractory brain and/or leptomeningeal metastasis were enrolled and treated with intrathecal pemetrexed, there were 40 cases in cohort 1 with refractory brain metastasis and 40 cases in cohort 2 with leptomeningeal metastasis.Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms. The study is expected to commence recruitment in mainland China in about September 2024. It is expected that the trial will end in April 2026.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
- •Age ≥ 18 years.
- •Histopathology is confirmed small cell lung cancer .
- •4.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
- •5.Patients with brain progression after whole-brain radiotherapy.
- •Predicted survival ≥ 12 weeks. .
- •Adequate bone marrow hematopoiesis and organ function.
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
Cohort 1
Small Cell Lung Cancer patient with Refractory Brain Metastases
干预措施: Intrathecal Pemetrexed (Drug)
Cohort 2
Small Cell Lung Cancer patient with Leptomeningeal Metastasis
干预措施: Intrathecal Pemetrexed (Drug)
结局指标
主要结局
Overall Survival
时间窗: Time from first subject dose to study completion, or up to last follow up
OS was defined as the duration from the start of intrathecal pemetrexed to patient death
次要结局
- Adverse events (AEs)(Time from first subject dose to study completion, or up to 36 month)
- Intracranial progression-free survival (I-PFS)(Time from first subject dose to study completion, or up to 36 month)
- Intracranial Objective Response Rate (I-ORR)(Time from first subject dose to study completion, or up to 36 month)
- clinical remission rate(Time from first subject dose to study completion, or up to 36 month)
研究者
Yongchang Zhang
Head of Medical Oncology, Director of Early Clinical Trial Center
Hunan Province Tumor Hospital