Precision Oncology Platform for Prostate Cancer

Monday, December 7, 2015

Dr. Kim Chi, Co-Chair of Canadian Cancer Trials Group's Genitourinary Site Committee and medical oncologist at the British Columbia Cancer Agency in Vancouver, has been awarded $500,000 from the Canadian Cancer Clinical Trials Network (3CTN) for the support of an exciting new IND Program suite of trials in castrate resistant prostate cancer, "Precision Oncology Platform for Prostate Cancer: A Phase 2 Umbrella Trial for Patients with Metastatic Castration Resistant Prostate Cancer."  This grant, which includes co-applicants from Canadian Cancer Trials Group and cancer centres across Canada, will be used to support a Master Screening Protocol and at least 4 planned phase II trials testing 7 or more different new drugs in CRPC.

The advent of high-throughput genomics has set the scene for “precision medicine”, whereby targeted therapy can be matched to distinct genomic and molecular aberrations within an individual patient’s cancer. A barrier to introducing precision medicine for patients with metastatic castration-resistant prostate cancer (CRPC) is obtaining relevant tumour tissue for molecular profiling which can be applied to multicentre trials and translated to community practise. Assays for gene copy number (CN) profiling and sequencing of circulating cell-free DNA (cfDNA) from plasma of CRPC patients have been developed that have identified genetic aberrations linked to clinical outcomes. Thus, these minimally-invasive assays represent a potential tool for testing a precision medicine approach to patients with CRPC. The goal of Dr. Chi's project is to evaluate the use of cfDNA profiling to select treatments for patients with CRPC.

The specific aims are to: (1) identify genomic alterations (tumour associated and germline) in a cohort of 300 CRPC patients; and (2) to establish an “umbrella” clinical trial matching CRPC patients with systemic therapy based on aberrations detected in Aim 1. To address these aims, with Dr. Chi, the Canadian Cancer Trials Group will conduct a multi-centre Canadian study that will enrol CRPC patients progressing after next-generation androgen receptor (AR) targeted therapy. Plasma will be collected and cfDNA extracted. A subset of patients will also undergo metastatic biopsies. Genomic profiling will be performed using deep targeted sequencing with custom NimbleGen SeqCap EZ Choice Library and Illumina sequencing platforms. In Year 1, the goal will be to establish feasibility and patients will be initially directed to active trials at participating centres. During Year 1, an umbrella trial will also be develop and activate which will accrue during Years 1-3.

This project will help validate the utility of cfDNA for genomic profiling of CRPC, contribute to understanding the molecular landscape of CRPC, establish the first umbrella trial for CRPC patients who have limited treatment options, and potentially identify new treatments and predictive biomarkers for the disease. The study will also establish a cross-Canada platform for the genomic profiling of CRPC patients and capability for the ongoing and efficient clinical testing of investigational agents in a molecularly-defined cohort of CRPC patients.