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

项目概要/摘要 据估计，每年有10万名患者被诊断患有原发性肝癌或胰腺癌， 许多患者会发生肝转移。不幸的是，这些患者中的绝大多数都不是 手术切除是唯一可靠的治愈性治疗方法，可获得5年生存率 对于原发性疾病患者，约为10%至20%。临床上的挑战是， 肿瘤形成于器官深处，靠近主要血管、胆管或神经， 的拔除.计算机控制电穿孔（ACE）是一种新的微创技术， PI用于治疗不可手术的肿瘤。这种治疗方法使用短暂的电脉冲来破坏细胞的稳定性 膜，并诱导坏死和凋亡细胞死亡的可调组合。我们已经验证了反- ACE对体外模型、小动物肿瘤模型和80多个兽医临床试验的癌症疗效 例在这个学术-工业合作伙伴关系提案中，我们将把这种经过验证的技术从实验室 通过开发临床仪器和配套的一次性施源器，这 将在猪肝模型中对仪器进行确认，以生成510（k）监管所需的数据 意见书。新系统的抗肿瘤疗效将在22只犬肝脏的队列中得到证实 NCSU兽医学院收治的癌症患者。本研究的数据将支持上市前 针对肿瘤适应症的上市前批准（PMA）监管申报，并提供必要的数据以证明 人体临床试验为了实现这些目标，我们组建了一个多学科的生物医学团队， 工程师、免疫学家、兽医、肝胆病理学家和介入肿瘤学家。发展 临床系统和一次性施用器的工作将由两个工业合作伙伴完成：梯度 Medical Inc. Nocturnal Product Development LLC.这些合作伙伴在以下领域拥有丰富的经验： 脉冲电场设备的开发，I、II和III类医疗器械的商业化，质量 系统管理（GMP/GLP）以及CE、510（k）和PMA监管提交。拟议工作 将导致开发出适合临床试验和商业化的完整医疗器械，沿着 提供支持提交FDA监管文件所需的数据。这项工作将通过四个 具体目标：（1）表征用于真实的治疗监测的微处理器，（2）设计和微处理器 适用于法规评估的临床ACE脉冲发生系统，（3）ACE的表征 在大型动物临床模型中的治疗，（4）评价ACE对自发性 犬肝细胞癌

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.