While androgen-deprivation therapy (ADT) demonstrates antitumor activity in mHSPC with prolonged disease control, resistance ultimately occurs and patients die of castration-resistant PC (CRPC). Approximately 10-50% of PC subjects develop CRPC in
This international, randomized, double-blind, placebo-controlled, phase 3 trial (NCT02799602) is being conducted in 23 countries. 1300 men with newly diagnosed mHSPC will be randomized 1:1 to either 600 mg (2 × 300 mg) darolutamide BID with food, equivalent to a total daily dose of 1200 mg or placebo, both with ADT + docetaxel (6 cycles after randomization), and stratified by extent of disease and alkaline phosphatase levels. Key inclusion criteria are confirmed PC with documented metastases, started ADT ± first-generation androgen inhibition therapy ≤12 wk before randomization, and Eastern Cooperative Oncology Group performance status 0 or 1. The primary objective is to show superior overall survival with darolutamide vs placebo, both with ADT + docetaxel. Secondary end points include time to CRPC, initiation of subsequent anticancer therapy, symptomatic skeletal event-free survival (SSE-FS), time to first SSE, initiation of opioid use, pain progression, and worsening of physical symptoms, all measured at 12-wk intervals. Safety will be assessed. The trial is open for enrollment, FPFV was in November 2016, and >110 sites in 16 countries are enrolling.
Clinical trial identification
Legal entity responsible for the study
Funded by Bayer. Darolutamide was discovered at Orion Corporation and is being jointly developed with Bayer.
M.R. Smith: Consultant for Bayer and Janssen. F. Saad: Consultant, honoraria, research funding from Bayer, Sanofi, Janssen, and Astellas. M. Hussain: Contract to conduct the clinical trial. C.N. Sternberg: Personal fees from Janssen, Sanofi, Astellas, Clovis, Bayer, and Ferring, outside the submitted work. K. Fizazi: Honoraria from Astellas, AstraZeneca, Bayer, Clovis, Curevac, Genentech, Janssen, Orion, and Sanofi. E.D. Crawford: Consultant for Bayer, MDx, Genomic Health, Janssen, Dendreon, and Ferring; honoraria from Bayer and involved in trials with the NIH and University of Colorado Cancer Center; family member employed by Dendreon. K. Yamada: Employee of Bayer US. C. Kappeler: Employee of Bayer AG and own Bayer shares. I. Kuss: Employee of Bayer AG. B. Tombal: Grants and other fees received from Bayer, Astellas, Ferring, and Sanofi; personal fees from Medivation and Janssen.