Tumor Monorail Device for Serial Glioblastoma Biopsy

项目摘要/摘要 胶质母细胞瘤(GBM)是最常见和最致命的恶性脑肿瘤之一， 患者生存期为12-15个月，5年生存率不到5%。目前的治疗标准是 GBM包括手术切除、放疗和化疗。然而，由于异质性和 GBM肿瘤细胞的侵袭性有很高的复发率(~80%)，导致生存惨淡 50多年来没有显著变化的利率。改善这些问题的主要障碍之一是- 随之而来的是缺乏可靠和准确的手段来监测肿瘤的进展和治疗反应。这个 目前的标准肿瘤监测方法，直接组织活检和外部成像，不能安全地 提供有关肿瘤进展和治疗反应的准确、集中、纵向的信息 将允许临床医生修改治疗方案以改善生存结果。在这里，我们提出了肿瘤 单轨作为一个平台，允许直接、连续地访问肿瘤材料，提供关于 这将帮助临床医生改善积极的治疗管理和患者的生存。 肿瘤单轨是一个突破性的指定设备，并已成为多个FDA预分项的主题 特派团会议以及广泛的核查和生物兼容性测试。通过利用设计和材料本身- 具有长期安全临床使用历史的选择，肿瘤单轨可以安全地提供访问这一典型 在门诊环境中无法接触到的肿瘤。这将为临床医生提供前所未有的信息量- 关于肿瘤遗传学和治疗反应的实时信息对改善预后至关重要。 是来治疗GBM的。这种范式转换诊断工具的潜在影响是广泛的， 包括提高现有护理标准和新治疗方案的疗效，增加临床 通过加快患者安置和数据收集来提高试验效率，消除治疗效果的不确定性 Cacy和成像中固有的肿瘤进展，等等。 该方案的目标是将肿瘤单轨作为一个平台进行优化和临床翻译。 GBM纵向抽样表。在提案的第1阶段中，我们将首先优化采样 设备中的能力和蜂窝迁移，并执行多个临床前验证测试，这将改善 易用性和轻松的监管审批。在第二阶段中，我们将协同验证设备的功效 在啮齿动物模型中进行标准护理治疗，并执行FDA要求的更多临床前测试，这将 确认该设备的长期可外植性、临床可用性和快速临床翻译的准备。 这些活动将确保肿瘤单轨列车处于良好的位置，以便提交调查报告- 副豁免(IDE)、临床翻译和快速采用，为重点关注的GBM提供新的治疗途径 关于积极的疾病管理和个性化的、有针对性的反应治疗，这将使临床医生能够 实时定制干预措施，增加数十年来停滞不前的患者结果。

Project Summary/Abstract Glioblastoma (GBM) is one of the most common and deadliest form of malignant brain tumors, with median patient survival of 12-15 months and five-year survival of less than 5%. The current standard of therapy for GBM comprises surgical resection then radiation and chemotherapy. However, due to the heterogeneity and invasive nature of GBM tumor cells there is a high rate (~80%) of tumor recurrence, leading to dismal survival rates that have not changed significantly in over 50 years. One of the primary hurdles to improving these out- comes is the lack of reliable and accurate means to monitor tumor progression and treatment response. The current standard methods of tumor monitoring, direct tissue biopsy and external imaging, are not able to safely provide accurate, focal, longitudinal information about the tumor progression and treatment response that would allow clinicians to modify treatment regimen to improve survival outcomes. Here we propose the Tumor Monorail as a platform that allows direct, serial access to tumor material, providing critical information about tumors in real time that will help clinicians improve active treatment management and patient survival. The Tumor Monorail is a Breakthrough Designated device and has been the subject of multiple FDA pre-sub- mission meetings and extensive verification and biocompatibility testing. By leveraging design and material se- lections with a long history of safe clinical use, the Tumor Monorail can safely provide access to this typically inaccessible tumor in an outpatient setting. This will provide clinicians with an unprecedented amount of infor- mation about tumor genetics and treatment response in real time that is critically important to improving out- comes for the treatment of GBM. The potential impact of this paradigm shifting diagnostic tool is wide ranging, including enhancing the efficacy of current standard of care and novel treatment regimens, increasing clinical trial efficiency by accelerating patient placement and data collection, removing uncertainty about treatment effi- cacy and tumor progression inherent in imaging, and more. The aims of this proposal are focused on optimization and clinical translation of the Tumor Monorail as a plat- form for longitudinal GBM sampling. In the Phase 1 portion of the proposal we will first optimize the sampling ability and cellular migration in the device and perform multiple pre-clinical verification tests that will improve usability and ease regulatory approval. In the Phase II portion we will validate the device efficacy in concert with standard of care treatment in a rodent model and perform more FDA requested pre-clinical testing that will confirm long term explantability, clinical usability, and preparation of the device for rapid clinical translation. These activities will ensure that the Tumor Monorail is well positioned for submission of an Investigational De- vice Exemption (IDE), clinical translation, and rapid adoption to provide a new treatment path for GBM focused on active disease management and individually targeted, responsive treatment that would allow clinicians to tailor interventions in real time, increasing patient outcomes that have been stagnant for decades.