Academic-Industrial Partnership to Develop Clinical Tools for Algorithmic Irreversible Electroporation of Inoperable Tumors

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Project Summary / Abstract An estimated 100,000 patients are diagnosed with primary liver or pancreatic cancer per year with an even larger number of patients will developing liver metastasis. Unfortunately, the vast majority of these patients are not candidates for surgical resection, which is the only reliably curative treatment, yielding a five year survival rate of approximately between 10 and 20% for patients with primary disease. The clinical challenge is that most tumors form deep within organs, near major blood vessels, bile ducts, or nerves which complicate surgical removal. Algorithmically Controlled Electroporation (ACE) is a new minimally invasive technique invented by the PI for the treatment of inoperable tumors. This treatment uses brief electrical pulses to destabilize the cell membrane and induce a tunable combination of necrotic and apoptotic cell death. We have validated the anti- cancer efficacy of ACE against in vitro models, small animal tumor models, and in over 80 veterinary clinical cases. In this Academic-Industrial Partnership proposal we will transition this validated technology from bench to bedside through the development of a clinical instrument and matching disposable applicators. This instrumentation will be validated in a porcine liver model to generate data necessary for 510(k) regulatory submissions. The anti-tumor efficacy of the new system will then be demonstrated in a cohort of 22 canine liver cancer patients admitted to the NCSU College of Veterinary Medicine. Data from this study will support premarket approval (PMA) regulatory submissions targeting an oncology indication and provide the necessary data to justify human clinical trials. To accomplish these goals we have assembled a multi-disciplinary team of biomedical engineers, immunologists, veterinarians, hepatobiliary pathologists, and interventional oncologists. Development work for the clinical system and the disposable applicators will be completed by two industrial partners: Gradient Medical Inc. and Nocturnal Product Development LLC. These partners have extensive experience in the development of pulsed electric field devices, commercialization of Class I, II, & III medical devices, quality systems management (GMP/GLP) as well as CE, 510(k), and PMA regulatory submissions. The proposed work will result in the development of a complete medical device suitable for clinical trials and commercialization along with the data necessary to support submission of FDA regulatory filings. This work will be accomplished via four specific aims: (1) Characterization of Metrics for Real Time Treatment Monitoring, (2) Design and Validate Clinical ACE Pulse Generation System Suitable for Regulatory Evaluation, (3) Characterization of ACE Treatments In a Large Animal Clinical Model, (4) Evaluate Safety and Efficacy of ACE Against Spontaneous Canine Hepatocellular Carcinoma.