Prostate cancer (PCa) is the most common cancer in men. In the majority of men, the disease will remain in theprostate and not impact survival. Nonetheless, over 30,000 men die from prostate cancer each year, indicatingclear unmet need for improvements in treatment options. While early stage prostate cancer is treated with eitheractive surveillance, prostatectomy or prostate radiation, higher risk unfavorable localized prostate cancer oftenbenefits from the addition of hormonal therapy. However, these therapeutic benefits come with undesirable sideeffects including an increased risk of cardiovascular disease, metabolic syndrome, osteoporosis, and loss oflibido and sexual function. As such, the benefits of adjuvant hormonal therapy are countervailed in men whohave one or more comorbid conditions, leading to poor compliance and non-adherence to physicianrecommendations. The ability to provide localized hormonal therapy would provide a novel strategy to deliveradjuvant 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, toprovide a tolerable, effective, long-term option for men who may otherwise forego hormonal therapy due to sideeffects. To date, we have successfully tested prototype implant devices in proof of concept and preclinical studiesusing relevant mouse and dog models. A critical element to the use of the implant involves safe and minimallyinvasive placement into the affected prostate tumor using an insertion device. A novel insertion device wasdesigned 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 forspecific insertion into tumors from men planning to undergo prostate radiation, with the goals of enablingplacement 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 localizedhormonal drug delivery in men undergoing radiation therapy for unfavorable early stage prostate cancer. Tofacilitate this study, this application would support the following aims: 1) redesign and optimization of the implantinsertion device; 2) manufacture of implants / insertion device to support the clinical study and; 3) conduct testingto confirm that implants and insertion devices are suitable for human use, sustain radiation therapy and establishthe shelf life of the implant product. Together these aims ready this promising product for FDA-approval of theplanned 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 subsequentPhase 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. Affect ; Androgen Antagonists ; Anti-Androgen ; Anti-Androgen Agents ; Antiandrogen Agents ; Antiandrogens ; androgen inhibitor ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Clinical Research ; Clinical Study ; Clinical Trials ; comorbidity ; co-morbid ; co-morbidity ; Disease ; Disorder ; Canis familiaris ; Canine Species ; Dogs ; Dogs Mammals ; canine ; domestic dog ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Elements ; Feasibility Studies ; Gamma Rays ; Gamma Radiation ; γ-Radiation ; γ-Ray ; Goals ; Health ; Human ; Modern Man ; implantable device ; biomedical implant ; implant device ; indwelling device ; Implantation procedure ; implant placement ; implant procedure ; indexing ; Libido ; sex drive ; male ; men ; men's ; Mus ; Mice ; Mice Mammals ; Murine ; Needles ; Osteoporosis ; Physicians ; Production ; Prostate ; Prostate Gland ; Prostatic Gland ; Prostatectomy ; Prostatic Neoplasms ; Prostate Neoplasms ; Prostate Tumor ; Prostatic Neoplasia ; Radiation therapy ; Radiotherapeutics ; Radiotherapy ; radiation treatment ; radio-therapy ; treatment with radiation ; Recommendation ; Safety ; Silicones ; Testing ; Vacuum ; Work ; Drug Delivery Systems ; Drug Delivery ; Guidelines ; analytical method ; base ; improved ; Clinical ; Phase ; Ensure ; hormone therapy ; Endocrine Therapy ; Hormonal Therapy ; Collaborations ; Letters ; Bicalutamide ; Casodex ; Cosudex ; Therapeutic ; Exposure to ; tool ; Filamentous Fungi ; Molds ; Malignant Tumor of the Prostate ; Malignant prostatic tumor ; Prostate CA ; Prostate Cancer ; Prostatic Cancer ; Malignant neoplasm of prostate ; Life ; Clinic ; System ; Hormonal ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; meetings ; experience ; Adjuvant Therapy ; sterile ; Sterility ; novel ; Devices ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Radiation ; Modeling ; Metabolic syndrome ; cardiovascular disease risk ; cardiovascular disorder risk ; Pharmaceutical Agent ; Pharmaceuticals ; Pharmacological Substance ; Pharmacologic Substance ; preventing ; prevent ; Address ; Data ; NCI Organization ; National Cancer Institute ; Process ; Adjuvant ; preclinical study ; pre-clinical study ; Sex Functioning ; sexual functioning ; design ; designing ; novel strategies ; new approaches ; novel approaches ; novel strategy ; human study ; innovation ; innovate ; innovative ; Implant ; Early treatment ; early therapy ; implantation ; usability ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; prototype ; tumor ; high risk ; public health relevance ; minimally invasive ; product development ; stability testing ; Sterilization ; safety and feasibility ; efficacy study ; first-in-human ; first in man ; side effect ;
