{
  "abstract": "Introduction The prolonged survival of lung cancer patients is accompanied by an increasing incidence of leptomeningeal metastases (LM). Patients with LM have a poor prognosis, significantly impacting their quality of life and overall survival. Recent studies have shown that while intrathecal pemetrexed (IP) can improve symptoms and confer a survival benefit in non-small cell lung cancer (NSCLC) patients with LM, drug resistance remains a significant challenge. As for systemic therapy, intravenous bevacizumab combined with chemotherapy has demonstrated clinical benefits in NSCLC patients. However, clinical data on intrathecal bevacizumab remain scarce. Therefore, this study aims to preliminarily explore the efficacy and safety of intrathecal pemetrexed and bevacizumab in the treatment of NSCLC patients with LM.Methods and analysis This is a single-centre, single-arm, prospective, investigator-initiated phase Ia clinical trial sponsored by Shanghai Chest Hospital, involving patients with advanced NSCLC and LM. Participants will be enrolled and allocated into two predefined cohorts. Cohort A: six participants will receive IP monotherapy for safety exploration. Cohort B: participants will receive intrathecal pemetrexed and bevacizumab. Pemetrexed will be administered at a fixed dose, while the dosage exploration for bevacizumab will employ a combination of a 3+3 design and an accelerated titration design (ATD). The primary endpoint is the safety and the secondary endpoint is the overall survival (OS).Ethics and dissemination This study protocol (Version 1.1, dated 8 October 2024) was approved by the Ethics Commission of Shanghai Chest Hospital (IS24103) on 23 October 2024. Trial results will be published in a peer-reviewed journal.Trial registration number NCT06663306, ClinicalTrials.gov.",
  "authors": [
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Yanbin Kuang"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Jiajun Teng"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Weimin Wang"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Bo Zhang"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Lei Cheng"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Yao Zhang"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Wanting Liu"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Zhiqiang Gao"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Wei Nie"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Liwen Xiong"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Chunlei Shi"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Wei Zhang"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Yuqing Lou"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Baohui Han"
    },
    {
      "affiliations": [
        "Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Hua Zhong"
    }
  ],
  "title": "Safety and efficacy of intrathecal pemetrexed and bevacizumab in non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM): protocol for a single-arm, prospective, phase Ia trial",
  "uid": "e3ccf7cd-1838-565b-b561-f2634b00fc59"
}