Rucaparib in Patients with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) A Phase II Study - Emmanuel Antonarakis

Emmanuel Antonarakis introduces the Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH). The aim of this Phase II clinical trial is to find out if the study drug rucaparib leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene involved in repairing DNA damage.

The research will also examine if rucaparib is safe in individuals with metastatic prostate cancer. Prior research studies have shown that drugs like rucaparib can be of benefit to patients with advanced metastatic prostate cancer who are resistant to androgen deprivation therapy AND who carry a mutation in a DNA repair gene. This study is designed to evaluate if rucaparib will be an effective treatment for these patients earlier in their treatment course (for example, prior to the start of medicines that lower testosterone level). It is unknown whether rucaparib will have the same benefit in men with metastatic prostate cancer carrying a mutation in a DNA repair gene, prior to the use of medicines that lower your testosterone level. With respect to germline mutations, a recent study found that the incidence of inherited DNA-repair gene alterations in metastatic prostate cancer to be significantly higher (11.8%) than in both men with localized prostate cancer (4.6%) and in the general population at large (2.7%). Specifically, mutations in 7 genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, RAD51D, GEN1) were significantly enriched in patients with metastatic prostate cancer compared to the general population. These findings suggest that a subset of men are more likely to develop metastatic prostate cancer (i.e. those with germline mutations in DNA-repair genes) and may potentially benefit from PARPi therapy. 

Biographies:

Emmanuel Stylianos Antonarakis, M.B.B.Ch. Dr Antonarakis is an Associate Professor of Oncology and Urology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. He obtained his medical degree from the University of Wales College of Medicine (United Kingdom) in 2003, and then completed a Residency in Internal Medicine at the Johns Hopkins Bayview Medical Center, followed by a Fellowship in Medical Oncology at the Johns Hopkins Hospital. In 2010, he joined the Johns Hopkins faculty as an attending physician and translational researcher. Dr Antonarakis’ clinical interest is the management of prostate cancer and other genitourinary malignancies (cancers of the bladder, kidney and testis). His research focuses on drug development and clinical trial design for patients with prostate cancer. More specifically, he is interested in developing novel androgen-directed therapies as well as immunotherapies for men with recurrent or advanced prostate cancer. He also has an interest in biomarker development, specifically the clinical validation of the AR-V7 biomarker. He is currently the PI of several phase II and III prostate cancer trials, and is an active member of the Prostate Cancer Clinical Trials Consortium (PCCTC) and the Eastern Cooperative Oncology Group (ECOG) as well as the NCI Prostate Cancer Task Force. He serves on the Editorial Board of several oncology journals, including the Journal of Clinical Oncology. He is the author of over 110 peer-reviewed articles, and several book chapters.

Alicia Morgans, MD, MPH

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