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

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.