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

项目摘要 根据母公司赠款奖2 R44 CA 224460，先进的化疗技术（ACT）开发了一种 植入式离子导入化疗输送装置（ACT-IOP-003），便于输注广泛的 将各种化疗剂直接注入到它们打算治疗的癌症中，从而最小化全身性 毒性暴露ACT继续专注于用吉西他滨治疗胰腺癌， 提议胰腺癌的五年生存率不到10%，并且依赖手术作为唯一的治疗方法。 治愈的机会。40%的患者由于肿瘤扩展到附近的主要区域而不适合手术 血管或神经。ACT将植入该装置，该装置使用离子电渗原理输送药物， 直接进入肿瘤，并通过终止于皮肤中的导管将该装置连接到体外， 端口在母公司申请和获奖中，ACT在临床前器械的基础上创建了临床质量器械 在广泛的实验室和动物试验中使用，后者显示出非常少的全身吉西他滨递送 当使用离子电渗法靶向药物递送到胰腺时，同时显示出显著的肿瘤消退。在 在该申请中，ACT建议使用ACT-IOP-003系统进行首次人体1a期试验， 升级临床前器械以进行腹腔镜植入，开发适应性皮肤端口设计， 腹膜设计导管技术，升级其定制直流控制器，使其具有可用性和人为因素 改进，并制定GMP生产工艺，以生产临床器械并进行安全和 有效性测试，以确保器械可安全用于人体。拟议的研究将进一步作为下一个 器械开发的关键步骤和靶向输送的概念验证 通过所述装置增加化学治疗剂到达目标的能力，同时减少化学治疗剂的剂量。 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.