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

项目总结 在父母资助奖2R44CA224460下，先进化疗技术公司(ACT)开发了一种 植入式离子导入化疗给药装置(ACT-IOP-003)，便于广泛的输注 各种化疗药物直接进入他们打算治疗的癌症，从而最大限度地减少系统性 接触有毒物质。ACT继续专注于用吉西他滨治疗胰腺癌 求婚。胰腺癌的五年存活率不到10%，唯一依赖手术的是 治愈的机会。40%的患者由于肿瘤扩散到附近的主要部位而不符合手术条件 血管或神经。ACT将植入该装置，该装置利用离子导入原理输送药物， 直接进入肿瘤，并通过端接在皮肤上的导管将设备连接到体外 左舷。在母公司的申请和奖励中，ACT基于临床前设备创建了一种临床质量设备 在广泛的试验台和动物试验中，后者几乎没有全身给药。 当使用离子导入向胰腺靶向给药时，肿瘤有明显的消退。在……里面 这项申请，ACT建议使用ACT-IOP-003系统进行首个人类1a期试验， 升级腹腔镜植入物的临床前设备，开发适合的皮肤端口设计 腹膜设计导管技术，升级其定制DC控制器，使其具有易用性和人为因素 改进，并开发GMP制造工艺以生产临床设备并进行安全和 功效测试，以确保设备对人类使用是安全的。拟议的研究将进一步作为下一步 设备开发的关键步骤和有针对性地交付的概念验证演示 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 Under the parent grant award 2R44CA224460, Advanced Chemotherapy Technologies (ACT) developed an Implantable Iontophoresis Chemotherapy Delivery Device (ACT-IOP-003) that facilitates the infusion of a wide variety of chemotherapy agents directly into the cancer they are intended to treat, thereby minimizing systemic toxic exposure. ACT continues to focus specifically on treating pancreatic cancer with gemcitabine for this proposal. Pancreatic cancer has a five-year survival rate of less than 10% 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. In the parent application and award, ACT has created a clinical quality device based on a pre-clinical device used in extensive bench top and animal testing, the latter 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 conduct the first-in-human Phase 1a trial using the ACT-IOP-003 System, upgrade the preclinical device for laparoscopic implantation, develop an adapted skin port design based on peritoneal design catheter technology, upgrade their custom DC controller with usability and human factors improvements, and develop GMP manufacturing processes to produce clinical devices and conduct safety and efficacy testing to ensure the device is safe for human use. The proposed studies will further serve as the next 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.