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

项目摘要/摘要 据估计，每年有10万名患者被诊断为原发性肝癌或胰腺癌，而且 有多少患者会发生肝转移。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根治方法，可获得五年存活率。 对于患有原发病的患者，大约在10%到20%之间。临床上最大的挑战是 肿瘤在器官深处、主要血管、胆管或神经附近形成，使外科手术复杂化。 移走。算法控制电穿孔(ACE)是由美国医学会发明的一种新型微创技术 PI用于治疗不能手术的肿瘤。这种治疗使用短暂的电脉冲来破坏细胞的稳定 膜并诱导可调节的坏死性和凋亡性细胞死亡的组合。我们已经确认了反- 血管紧张素转换酶对体外模型、小动物肿瘤模型和80多个兽医临床的肿瘤疗效 案子。在这份学术-工业伙伴关系提案中，我们将把这项经过验证的技术从BASE过渡到 通过开发一种临床仪器和与之配套的一次性敷贴器，使患者能够在床边工作。这 仪器将在猪肝脏模型中进行验证，以生成510(K)监管所需的数据 意见书。然后，新系统的抗肿瘤效果将在22只狗的肝脏队列中得到验证。 癌症患者被NCSU兽医学院录取。这项研究的数据将支持上市前 批准(PMA)针对肿瘤学适应症的监管提交，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 临床系统和一次性涂抹器的工作将由两个行业合作伙伴完成：GRADER 医疗公司和夜间产品开发有限责任公司。这些合作伙伴在以下领域拥有丰富的经验 脉冲电场设备的发展、I、II、III类医疗设备的商业化、质量 系统管理(GMP/GLP)以及CE、510(K)和PMA法规提交。拟议中的工作 将导致开发出适合临床试验和商业化的完整医疗设备 拥有支持提交FDA监管文件所需的数据。这项工作将通过四个途径完成 具体目标：(1)实时治疗监测指标的表征；(2)设计和验证 适用于临床常规评估的血管紧张素转换酶脉冲发生系统，(3)血管紧张素转换酶特性 大动物临床模型治疗：(4)评价血管紧张素转换酶治疗自发性疾病的安全性和有效性 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.