DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Prostate Cancer Clinical Trials Consortium: Dana-Farber/Harvard Cancer Center

Principal Investigator: TAPLIN, MARY-ELLEN
Institution Receiving Award: DANA-FARBER CANCER INSTITUTE
Program: PCRP
Proposal Number: PC161021
Award Number: W81XWH-17-2-0017
Funding Mechanism: Clinical Consortium Research Site Award
Partnering Awards:
Award Amount: $1,310,000.00


TECHNICAL ABSTRACT

Expertise: Dana-Farber/Harvard Cancer Center (DF/HCC) has a team of genitourinary (GU) oncologists who are expert in prostate cancer clinical trials and drug development. Twelve physician trialists are supported by a dedicated team of regulatory specialists, project managers, clinical research coordinators, and research nurses. Our team is well published and played leadership roles in the approval of the recent new therapies for prostate cancer and the practice changing CHARTERED trial of early use of chemotherapy in hormone-sensitive prostate cancer. We are dedicated to trials that include tissue sampling to analysis mechanisms of tumor response and resistance. The depth of our expertise and multi-center collaborations is exemplified in our prostate SPORE (Specialized Program of Research Excellence) and Prostate Cancer Foundation (PCF)-Stand Up 2 Cancer (SU2C) programs.

Resources: DF/HCC has centralized research operations including scientific review, institutional review board, and multi-center trial monitoring and oversight. Unique to Dana-Farber clinical research is a well-established GU oncology clinical patient database (> 8,000 registered patients), blood and tissue repositories, genomics core, and GU-specific statisticians to support data collection and analysis.

Prostate Cancer Population: The DF/HCC patient population and specifically prostate cancer population is large. There are approximately 2,500 new prostate cancer patients seen at DF/HCC primary sites yearly and 200 prostate patients accrued to therapeutic trials. DF/HCC has identified prostate cancer mortality in black men as a priority. The DF/HCC together with the Prostate Health Educational Network, founded in 2003, launched a monthly support group for African-American men with prostate cancer. The group meets at Dana-Farber Cancer Institute (DFCI) and is facilitated by trained staff. DF/HCC and Prostate Health Education Network (PHEN) share responsibility for recruiting participants and for ensuring that the group addresses the participants’ interests and needs.

Study Design: The DFCI GU research program has depth in both basic science and clinical research. Within the Prostate Cancer Clinical Trials Consortium (PCCTC), we will focus on investigator-initiated, Phase 2 trials that have embedded tissue sampling for correlative analysis. Building on our past work in PCCTC, the two main areas of focus will be (1) neoadjuvant clinical trials of intense androgen deprivation therapy and (2) trials of novel therapy combinations in metastatic castration-resistant prostate cancer focusing on mechanisms of response/resistance. These trials will evaluate second-generation androgen signaling inhibitors alone and in combination with therapies including PARP inhibitors and immune check point inhibitors.

Clinical Impact: DF/HCC participation in the PCCTC will have major clinical impact. As part of PCCTC, we will be able to leverage resources from DFCI SPORE projects into clinical trials. DF/HCC participation in the PCF-SU2C prostate cancer dream team has established a clinical trial program that feeds metastatic tumor samples to genomic analysis; this program discovered the importance of DNA repair alterations in castration-resistant prostate cancer leading to new therapy approaches. There are many ongoing PCF-SU2C projects expected to have clinical impact. In addition, our well-established program of neoadjuvant trials in the high-risk localized prostate cancer population is poised to establish predictors of response to intense androgen deprivation in this setting and support Phase 3 trial programs to increase cure rates for these patients.