DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

PCRP Clinical Consortium: Duke University Clinical Research Site

Principal Investigator: GEORGE, DANIEL J
Institution Receiving Award: DUKE UNIVERSITY
Program: PCRP
Proposal Number: PC161026
Award Number: W81XWH-17-2-0021
Funding Mechanism: Clinical Consortium Research Site Award
Partnering Awards:
Award Amount: $1,272,000.00


TECHNICAL ABSTRACT

Expertise: Led by Drs. Daniel George and Andrew Armstrong in medical oncology, Duke has formed a highly collaborative and multidisciplinary team of prostate cancer (PC) clinical researchers and staff, joined together by the Duke Cancer Institute (DCI) infrastructure. With strong leadership and experience in urology (Drs. Judd Moul and Brant Inman), radiation oncology (Drs. W. Robert Lee and Bridget Koontz), translational research (Drs. Steven Patierno, Donald McDonnell, Smita Nair, Jiaoti Huang, Andrew Armstrong among others), and pathology (Dr. Jiaoti Huang), Duke has mature leaders engaged in high-impact PC focused research, all with 10 or more years of experience in the field. Drs. George, Armstrong, and Moul sit on multiple steering committees of large Phase II-III industry-sponsored trials and Drs. George and Armstrong, together with Dr. Susan Halabi in Biostatistics, are involved in the leadership of the genitourinary section of ALLIANCE, where they have led the way in biomarker and trial development efforts. Dr. Armstrong currently serves as correlative science chair of the current Phase III ALLIANCE A031201 trial of enzalutamide +/- abiraterone acetate and co-chairs PCWG3 [Prostate Cancer Working Group 3] and serves on the NCCN [National Comprehensive Cancer Network] PC guidelines panel. Duke has additionally led a large multicenter PCF [Prostate Cancer Foundation] Challenge Award focused on circulating molecular predictors of AR-therapy response and resistance being conducted through the PCCTC [Prostate Cancer Clinical Trials Consortium], and has developed a range of validated prognostic models and surrogacy biomarker studies in castration-resistant PC (CRPC). Finally, Duke clinical investigators have led and are currently leading over 18 multisite investigator initiated trials in PC across the disease state spectrum.

Resources: Within the DCI, we have established a robust clinical research infrastructure for overseeing project management, monitoring, data collection, and safety reporting for oncology trials. As a group, we include 15 investigators spanning urology, medical oncology, and radiation oncology, 10 research nurses, 4 regulatory coordinators, and 8 clinical trial assistants and data managers. We currently have over 60 clinical trials completed, open and accruing, and funded/planned in PC, including our DoD [Department of Defense] PCCTC trials. In addition, we have a shared resource for tissue biorepository and clinical database development. Institutional laboratory resources for multicenter database development, metastatic tumor tissue acquisition and processing, CTC [circulating tumor cell] profiling, and RNA expression analysis of tumor tissue are available. Other key institutional resources on campus include the DCI safety desk, DCI monitoring team, the Duke Clinical and Translational Institute (CTSI) supported by an NIH [National Institutes of Health] Clinical and Translational Science Award, multiple institutional shared resources for high-throughput DNA, RNA, and protein biomarker discovery and validation and patient derived xenograft development, and the Duke Clinical Research Institute (DCRI) for multicenter trial and registry development.

Population for PCCTC Trials: We have a robust PC patient population with patients seen across urology, medical oncology, and radiation oncology. African Americans make up approximately 24% of our patient demographic for clinic visits for PC, and are represented by approximately 20.5% of our PCCTC clinical research accrual. Each year we see over 300 men with CRPC and have accrued between 40-60 PC patients per year in PCCTC trials since 2007, including over 22% US Veterans. Over the last 2.5 years, we have seen our clinical trial volume increase and have accrued 194 subjects to PCCTC trials for an average of over 77 patients per year, making Duke one of the three top accruing consortium sites since 2013.

Study Design: Duke has built upon multiple high-impact thematic areas of clinical research including (1) PC immunotherapy, (2) biology of racial disparities, (3) biomarkers and mechanisms of lethal disease, and (4) multimodality trials in early-stage, aggressive PC. Proposed and funded trials include Oncolytic Poliovirus immunotherapy for men with metastatic CRPC (mCRPC), salvage apalutamide with ADT [androgen deprivation therapy] and radiation followed by adjuvant docetaxel in PSA [prostate-specific antigen] recurrent PC, a race-stratified trial of abiraterone and apalutamide in mCRPC, PDL-1 inhibition in neuroendocrine PC, and the 5000 patient international IRONMAN registry for advanced PC.

Clinical Impact: Duke continues to make a substantial impact in the field of PC through the DoD PCCTC through novel therapeutic approaches as well as through biomarker discovery and validation studies. We have prioritized clinical trials involving tissue and circulating biomarker collection and validation studies including CTC genomic characterization, and have led the way in standardizing fixed and frozen prostatectomy and metastatic tissue procurement across PCCTC institutions. Our high-impact thematic areas leverage the strengths of our laboratory/translational and pathology resources and clinical research infrastructure to understand the biology of CRPC progression, develop validated biomarkers to predict outcomes and track responses and resistance to therapy, and investigate novel approaches including hormonal, immunologic, cytotoxic, bone microenvironment, and molecularly targeted therapies to favorably impact the lives of men with PC.