Tumor Monorail Device for Serial Glioblastoma Biopsy

项目概要/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， 患者存活12 - 15个月，5年存活率低于5%。目前的治疗标准 GBM包括手术切除，然后放疗和化疗。然而，由于异质性和 GBM肿瘤细胞的侵袭性存在高的肿瘤复发率（~80%），导致令人沮丧的生存 50多年来没有发生重大变化。其中一个主要的障碍，以改善这些- 另一个问题是缺乏可靠和准确的手段来监测肿瘤进展和治疗反应。的 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 提供关于肿瘤进展和治疗反应的准确、局部、纵向信息， 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，连续访问肿瘤材料，提供关键信息， 真实的实时监测肿瘤，这将有助于临床医生改善积极的治疗管理和患者生存。 Tumor Monorail是一种突破性的指定器械，已成为多个FDA预分... 使命会议和广泛的验证和生物相容性试验。通过充分利用设计和材料， 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这种典型的 无法触及的肿瘤这将为临床医生提供前所未有的信息量- 关于肿瘤遗传学和真实的治疗反应的信息，这对改善 用于治疗GBM这种范式转变诊断工具的潜在影响是广泛的， 包括提高当前标准治疗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，消除治疗效果的不确定性，提高试验效率， cacy和肿瘤进展固有的成像，等等。 该提案的目的是将肿瘤单轨作为平台进行优化和临床转化， 纵向GBM取样表。在提案的第1阶段，我们将首先优化采样 并执行多项临床前验证测试， 可用性和易于监管批准。在II期部分，我们将共同验证器械的有效性 在啮齿动物模型中进行标准治疗，并进行更多FDA要求的临床前试验， 确认器械的长期稳定性、临床可用性和快速临床转化准备。 这些活动将确保Tumor Monorail能够很好地提交研究性报告， 副豁免（IDE），临床翻译和快速采用，为GBM提供新的治疗途径， 积极的疾病管理和个性化的针对性治疗，使临床医生能够 在真实的时间内定制干预措施，提高数十年来停滞不前的患者治疗效果。

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.