Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology

Prostate Cancer Analysis

The overall PATCH vision is designed for clinical care and research work to together toward improved care for those with prostate cancer (Figure 1). The resources necessary for successful translational research are substantial, and PATCH aims to streamline those resources. PATCH will support innovative, precision-based clinical research at the POPCaP COEs through its 5 arms.

Arm 1. Dedicated personnel ensure veteran access to trials in PATCH by giving patients and providers accurate information about available trial options; aiding veterans in traveling from home VA to a POPCaP COE for participation on a study; and maintaining the Committee for Veteran Participation in PATCH, where veterans will be represented and asked to provide input into the PATCH process.

Arm 2. Coordinators at the coordinating COE in Portland, Orgeon, train investigators and study staff at the local POPCaP COEs to ensure research can be performed in a safe and responsible way.

Arm 3. Personnel experienced in conducting clinical trials liaise with investigators at VA Central Institutional Review Board, monitor trials, build databases for appropriate and efficient data collection, and manage high-risk studies conducted under an Investigational New Drug application. This group works closely with biostatisticians to choose appropriate trial designs, estimate numbers of patients needed, and interpret data once they are collected.

Arm 4. Protocol development and data dissemination is coordinated by a group to assist investigators in drafting protocols and reviewing abstracts and manuscripts.

Arm 5. A core group manages contracts and budgets, as well as relationships between VA and industry, where funding and drugs may be obtained.

Perhaps most importantly, PATCH leverages the genetic data collected by POPCaP COEs to find patients for clinical trials. For example, the trials that examined olaparib and rucaparib assumed that the prevalence of HRD was about 25% in men with advanced prostate cancer.¹¹ As these trials began enrollment, however, researchers discovered that the prevalence was < 20%. In fact, the study of olaparib screened 4,425 patients at 206 sites in 20 countries to identify 778 (18% of screened) patients with HRD.⁴ With widespread sequencing within VA, it could be possible to identify a substantial number of patients who are already known to have the mutation of interest (Figure 2).

Clinical Trials

There are currently 2 clinical trials in PATCH; 4 additional trials await funding decisions, and more trials are in the concept stage. BRACeD (NCT04038502) is a phase 2 trial examining platinum and taxane chemotherapy in tumors with HRD (specifically, BRCA1, BRCA2, and PALB2). About 15% to 20% of men with advanced prostate cancer will have a DNA repair defect in the tumor that could make them eligible for this study. The primary endpoint is progression-free survival.

A second study, CHOMP (NCT04104893), is a phase 2 trial examining the efficacy of immunotherapy (PD-1 inhibition) in tumors having mismatch repair deficiency or CDK12-/-. Each of those is found in about 7% of men with metastatic prostate cancer, and full accrual of a trial with rare mutations could take 5 to 10 years without a systematic approach of sequencing and identifying potential participants. The primary endpoint is a composite of radiographic response by iRECIST (immune response evaluation criteria in solid tumors), progression-free survival at 6 months and prostate specific antigen reduction by ≥ 50% in ≤ 12 weeks. With 11 POPCaP COEs sequencing the tumors of every man with metastatic prostate cancer, identifying men with the appropriate mutation is possible. PATCH will aid the sites in recruitment through outreach and coordination of travel.