A novel implantable drug-eluting device that delivers an anti-androgen to the prostate to treat localized early stage prostate cancer

Abstract Prostate cancer (PCa) is the most common cancer in men. In the majority of men, the disease will remain in the prostate and not impact survival. Nonetheless, over 30,000 men die from prostate cancer each year, indicating clear unmet need for improvements in treatment options. While early stage prostate cancer is treated with either active surveillance, prostatectomy or prostate radiation, higher risk unfavorable localized prostate cancer often benefits from the addition of hormonal therapy. However, these therapeutic benefits come with undesirable side effects including an increased risk of cardiovascular disease, metabolic syndrome, osteoporosis, and loss of libido and sexual function. As such, the benefits of adjuvant hormonal therapy are countervailed in men who have one or more comorbid conditions, leading to poor compliance and non-adherence to physician recommendations. The ability to provide localized hormonal therapy would provide a novel strategy to deliver adjuvant therapy without the additional systemic side effects. To address this unmet need, we have designed a novel silicone based implantable device with the goal of local, controlled delivery of an anti-androgen, bicalutamide, in the prostate while minimizing systemic exposure, to provide a tolerable, effective, long-term option for men who may otherwise forego hormonal therapy due to side effects. To date, we have successfully tested prototype implant devices in proof of concept and preclinical studies using relevant mouse and dog models. A critical element to the use of the implant involves safe and minimally invasive placement into the affected prostate tumor using an insertion device. A novel insertion device was designed to enable sterile, reliable transfer of the implant to surgical tools used for transperineal implantation, and also function as primary package for the implants. Our initial prototype of the device needs to be tailored for specific insertion into tumors from men planning to undergo prostate radiation, with the goals of enabling placement of multiple implants to tumors while preventing yield losses and meeting manufacturing specifications. We plan to conduct a first-in-human study in collaboration with the National Cancer Institute (NCI) to test localized hormonal drug delivery in men undergoing radiation therapy for unfavorable early stage prostate cancer. To facilitate this study, this application would support the following aims: 1) redesign and optimization of the implant insertion device; 2) manufacture of implants / insertion device to support the clinical study and; 3) conduct testing to confirm that implants and insertion devices are suitable for human use, sustain radiation therapy and establish the shelf life of the implant product. Together these aims ready this promising product for FDA-approval of the planned clinical feasibility study. The team working on this project is highly experienced in combination (drug- device) and pharmaceutical product development and has successfully brought similar products to the clinic. The data from the feasibility study will establish safety of the approach and inform the design of a subsequent Phase 2 efficacy study where we plan to compare the implant against active surveillance.Public Health Relevance Prostate cancer remains the most common male cancer, with ~ 200,000 cases per year and hormonal therapy has clearly shown to benefit many of these men, however, systemic side effects often countervail the benefits. We have designed a novel drug-eluting implant/delivery system which includes a novel device insertion device that selectively delivers an anti-androgen to the prostate to treat localized early stage prostate cancer while minimizing systemic side effects. We plan to test this device in a clinical feasibility study in men undergoing prostate radiation.