Tumor Monorail Device for Serial Glioblastoma Biopsy

用于连续胶质母细胞瘤活检的肿瘤单轨装置

基本信息

批准号：
10760627
负责人：
Sean Meehan
金额：
$ 39.92万
依托单位：
EXVADE BIOSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10760627
关键词：
Acceleration Adoption Aftercare Award Biopsy Blood - brain barrier anatomy Brain Neoplasms Catheters Cells Chemotherapy and/or radiation Clinical Clinical Treatment Clinical Trials Data Data Collection Device Designs Device or Instrument Development Devices Diffuse Disease Disease Management Drug Screening Effectiveness Emerging Technologies Engineering Ensure Excision Fatality rate Foundations Funding Genetic Glioblastoma Grant Heterogeneity Human Image Implant In Vitro Individual Information Management Instruction International Intervention Lead Malignant neoplasm of brain Marketing Methods Molecular Molecular Profiling Monitor Nature Needles Operative Surgical Procedures Outcome Outpatients Patient-Focused Outcomes Patients Performance Phase Polyurethanes Positioning Attribute Preclinical Testing Preparation Primary Neoplasm Process Production Publishing Puncture biopsy Qualifying Recording of previous events Recurrence Recurrent tumor Risk Rodent Rodent Model Safety Sampling Silicones Speed Suggestion Survival Rate System Technology Testing Thinness Time Tissues Translations Treatment Efficacy Treatment Protocols Treatment outcome Tumor Tissue Uncertainty United States National Institutes of Health active method aggressive therapy biomaterial compatibility cell motility clinical translation clinically relevant copolymer design diagnostic tool effective therapy efficacy evaluation empowerment first-in-human imaging capabilities implantation improved improved outcome in vivo insight interest liquid biopsy meetings migration mortality nanofiber nanopolymer neoplastic cell novel pre-clinical preclinical development radiological imaging response safety and feasibility standard of care subcutaneous survival outcome treatment planning treatment response tumor tumor heterogeneity tumor progression usability virtual

项目摘要

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.

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，中位数为患者生存期为12-15个月，五年生存率低于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 肿瘤细胞具有侵袭性，肿瘤复发率很高（约 80%），导致生存率低下 50多年来未发生显着变化。改善这些输出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进展和治疗反应。这目前肿瘤监测的标准方法，直接组织活检和外部成像，无法安全地提供有关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。这里我们建议肿瘤单轨列车作为一个平台，允许直接、连续地访问肿瘤材料，提供有关肿瘤材料的关键信息实时监测肿瘤，这将有助于临床医生改善积极的治疗管理和患者的生存率。肿瘤单轨列车是一种突破性指定设备，并已成为 FDA 多项预分项的主题。任务会议以及广泛的验证和生物相容性测试。通过利用设计和材料科学具有悠久的临床安全使用历史，肿瘤单轨列车可以安全地提供这种典型的访问在门诊环境中难以接近的肿瘤。这将为临床医生提供前所未有的大量信息实时了解肿瘤遗传学和治疗反应，这对于改善预后至关重要用于治疗 GBM。这种范式转变诊断工具的潜在影响是广泛的，包括提高当前护理标准和新治疗方案的功效，增加临床通过加速患者安置和数据收集，消除治疗效果的不确定性，提高试验效率成像中固有的准确性和肿瘤进展等等。该提案的目标集中于肿瘤单轨作为平台的优化和临床转化。用于纵向 GBM 采样的表格。在提案的第一阶段部分，我们将首先优化采样设备中的能力和细胞迁移，并执行多项临床前验证测试，这将改善可用性并简化监管审批。在第二阶段部分，我们将协同验证设备功效在啮齿动物模型中进行标准护理治疗，并进行更多 FDA 要求的临床前测试，这将确认设备的长期可移植性、临床可用性以及快速临床转化的准备。这些活动将确保肿瘤单轨铁路能够很好地提交研究报告副豁免 (IDE)、临床转化和快速采用，为重点关注的 GBM 提供新的治疗路径积极的疾病管理和个体化、有针对性、反应灵敏的治疗，使临床医生能够实时定制干预措施，提高数十年来停滞不前的患者治疗效果。