Tumor Monorail Device for Serial Glioblastoma Biopsy

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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.