DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Prostate Cancer Clinical Trials Consortium: Johns Hopkins Kimmel Cancer Center Site

Principal Investigator: ANTONARAKIS, EMMANUEL
Institution Receiving Award: JOHNS HOPKINS UNIVERSITY
Program: PCRP
Proposal Number: PC161032
Award Number: W81XWH-17-2-0027
Funding Mechanism: Clinical Consortium Research Site Award
Partnering Awards:
Award Amount: $1,008,000.00


TECHNICAL ABSTRACT

Expertise: Our research team consists of the Principal Investigator (Dr. Antonarakis), three co-Investigators (Drs. Carducci, Eisenberger, and Paller), and a clinical research coordinator (Ms. Serina King). Dr. Antonarakis is an Associate Professor of Oncology who has led 22 Phase II or I/II studies in the past 8 years, of which 12 have been conducted through the Prostate Cancer Clinical Trials Consortium (PCCTC). He has also led biomarker studies to clinically validate the AR-V7 splice variant. Dr. Carducci is the AEGON Professor of Prostate Cancer Research and is also the Associate Director for Clinical Research, overseeing all clinical trials initiatives. Drs. Eisenberger and Paller are active translational clinicians who contribute to prostate cancer enrolments and clinical trial design. Ms. King is a certified research program coordinator who has worked with our group for 13 years (and with the PCCTC for 10 years); she is our most senior study coordinator and specifically works on multi-center prostate cancer studies.

Resources: The Johns Hopkins Kimmel Cancer Center (JHKCC) Prostate Cancer Program includes 31 faculty members spanning 8 Departments and 3 Schools within the University. Patients are enrolled to clinical trials from the Departments of Oncology, Urology and Radiation Oncology, as well as our Multi-Disciplinary Prostate Cancer Clinic. The Program currently has 9 research nurses, 9 data managers, 2 nurse practitioners, a program manager, and a regulatory specialist. In the preceding 6½ years (last 2 funding cycles), this Program has enrolled 2,028 prostate cancer patients to interventional clinical studies (averaging 312 patients/year), and 28% of these accruals have been to PCCTC trials. Since the last funding period (Sept 2014 to Aug 31, 2016), we have enrolled 106 men to PCCTC trials (averaging 53 patients/year), exceeding the 25/year target. Accruals of minority populations are at 17%, exceeding the 5% minority accrual target.

Prostate Cancer Population: Our Consortium-led trials will continue to target a diverse population ranging from the neoadjuvant/adjuvant population, to men with biochemical (PSA) recurrence, to men with advanced castration-resistant prostate cancer (CRPC). One of our unique institutional strengths at JHKCC is the conduct of clinical trial for men with hormone-sensitive PSA-recurrent prostate cancer, a population without any standard of care which comprises about 50% of our medical oncology referrals. In addition, we will continue to explore ways to increase accrual to minority populations; to do so, we have hired an Assistant Director of Diversity and Inclusion in Clinical Research to understand and overcome barriers to minority accrual.

Study Design: We plan to propose a series of hypothesis-driven translational trials evaluating androgen receptor (AR)-targeting therapies with embedded biomarker studies to understand resistance mechanisms, several immunotherapy studies focusing on novel agents as well as combinatorial strategies, and studies exploring poly-ADP ribose polymerase (PARP) inhibition. In addition, we aim to incorporate tumor-specific or host-specific biomarkers and/or novel imaging modalities (e.g., PSMA-directed PET scans) into at least half of these proposed trials. More specifically, we propose a study of the AR amino-terminal inhibitor EPI-506 in men with advanced CRPC; a study of ipilimumab plus nivolumab for men with AR-V7+ CRPC; two studies of pembrolizumab either used alone or combined with the TGF-beta receptor inhibitor, galunisertib, in men with CRPC; a pharmacodynamic neoadjuvant trial of the B7-H3 antibody enoblituzumab in men with high-risk localized disease; and a study using the PARP inhibitor olaparib in unselected patients with PSA-recurrent prostate cancer.

Clinical Impact: These proposed studies have the potential to lead to new therapies targeting the androgen axis, the PARP pathway, or modulating the immune system for therapeutic gain. They may also lead to an understanding of mechanisms of resistance to AR-directed therapies and immunotherapies. Moreover, they may suggest a role for PSMA-directed PET imaging in evaluating response/resistance to AR-targeting agents, PARP inhibitors and immunotherapy. Our overall aim is to strive to eliminate death from prostate cancer and enhance patient well-being.