Implantable iontophoresis chemotherapy delivery device for direct infusion of gemcitabine into pancreatic adenocarcinoma: Device development and First-in-Human clinical trial

项目总结 先进化疗技术公司(ACT)开发了一种专利植入式离子导入设备 这有助于将化疗药物直接注入癌症肿瘤，最大限度地减少对 血管系统和其他器官。ACT专门致力于治疗胰腺癌 吉西他滨适用于这一提议。胰腺癌的五年生存率不到7%，依赖于 手术是治愈的唯一机会。40%的患者因肿瘤扩大而不符合手术条件 进入附近的主要血管或神经。ACT将植入该设备，该设备使用 离子导入原理，直接进入肿瘤，并通过一种 导管在皮肤口终止。ACT设计了一种临床前设备，用于广泛的工作台和 动物试验，并将调整设计用于临床试验。动物模型显示的很少。 吉西他滨全身给药时，使用离子导入向胰腺靶向给药 肿瘤明显消退。在这一应用中，ACT建议重新设计临床前设备并开发 GMP生产流程以生产临床设备，并进行安全性和有效性测试，以确保 该设备对人类使用是安全的。该应用程序将包括一个有限的小型首次人体试验，它将 评估经胰腺离子导入吉西他滨的安全性。拟议的研究将有助于 作为设备开发和概念验证演示的关键一步， 通过该装置增加化疗药物到达靶点的能力，同时降低 系统性影响。

PROJECT SUMMARY Advanced Chemotherapy Technologies (ACT) has developed a proprietary implantable iontophoretic device that facilitates the infusion of chemotherapy agents directly into a cancer tumor, minimizing toxic exposure to the vascular system and other organs. ACT is focusing specifically on treating pancreatic cancer with gemcitabine for this proposal. Pancreatic cancer has a five-year survival rate of less than 7% and relies on surgery as the only opportunity for a cure. 40% of patients are not eligible for surgery due to tumor expansion into nearby major blood vessels or nerves. ACT will implant the device, which delivers the drug using iontophoresis principles, directly into the tumor, and connect the device to the outside of the body through a catheter terminated in a skin port. ACT has designed a pre-clinical device used in extensive bench top and animal testing and will adapt the design for clinical testing. The animal models demonstrated very little systemic gemcitabine delivery when using iontophoresis to target drug delivery to the pancreas while showing marked tumor regression. In this application, ACT proposes to redesign the preclinical device and develop GMP manufacturing processes to produce clinical devices and conduct safety and efficacy testing to ensure the device is safe for human use. This application will include a limited small first-in-human trial that will assess the safety of iontophoretic infusion of gemcitabine into the pancreas. The proposed studies will serve as a critical step in device development and proof-of-concept demonstration of the targeted delivery of the chemotherapeutic agents by the device increasing the ability of the agent to reach the target while decreasing systemic impact.