However, new agents with potent, often slight different, mechanisms of action continue to be developed and are competing for the same disease space. Darolutamide (DARO) is a new next-generation AR inhibitor which has shown strong activity and minimal toxicity in two phase I-II trials ARADES (Fizazi, Lancet Oncol 2014) and ARAFOR (Massard, Eur Urol 2016) and is currently being evaluated in a study in men with non-metastatic CRPC (ARAMIS trial). In contrast to Enza, DARO does not significantly penetrate the blood-brain barrier and this may reduce the risk of fatigue, cognitive impairment, and seizure..
This particular clinical trial (ODENZA) continues the work above in a phase II setting to specifically assess patient preference.
Study Design: Prospective, randomized, open-label, multicenter, cross-over phase II trial
Goal: Assess patient preference between DARO and Enza
Inclusion criteria: men with asymptomatic or mildly symptomatic mCRPC, performance status 0-1, and no prior next generation AR axis-targeted agent (ARAT).
Patients are randomized 1:1 to Enza or DARO initially followed by crossover to the other agent
Arm A: 12-week Enza followed by 12-week DARO
Arm B: 12-week DARO followed by 12-week Enza
Randomization stratified: performance status and prior treatment with a taxane for castration-sensitive prostate cancer (CSPC)
After patient questionnaire and investigator decision, patients are put continued on one of the two medications.
Goal accrual: 250 patients
Primary endpoint: Patient preference between DARO and Enza
This will be assessed after the second treatment period (when patients have taken both treatments)
Per the poster, the Prescott’s test will be used to analyze patient preference – though specifics were not given. In addition, other endpoints being assessed include: reasons for patient preference, dose modifications and time to dose modification, safety, fatigue (BFI), cognitive function as assessed by Cogstate computerized cognitive tests, depression screening (CES-D) test, frequency of falls.
Oncologic outcomes assessed include PSA declines using Waterfall plots after each treatment period, Progression-Free Survival (PFS), association between 4-weeks PSA value and PFS, incidence of cancer progression or death, and tumor response. At this time, the study is actively recruiting. By November 2017, 15 patients have been enrolled. 46 total centers will participate.
The study is recruiting. By February 13, 2018, 10 patients have been enrolled. Clinical trial information: NCT03314324
Presented by: Geraldine Martineau
CO-AUTHORS: Stéphanie Foulon, Jean-Christophe Eymard, Yohann Loriot, Giulia Baciarello, Jean Francois Berdah, Carole Helissey, Pernelle Lavaud, Florence Joly, Nadia Zaghdoud, Anne Sophie Hue, Karim Fizazi
INSTITUTION(S): Clinical Research Department, Institut Gustave Roussy, Villejuif, France; Institut Gustave Roussy, Villejuif, France; Institut Jean-Godinot, Reims, France; Institut Gustave Roussy, Villejuif Cedex, France; Gustave Roussy Cancer Campus, Villejuif, France; Clinique Sainte Marguerite, Hyères, France; HIA Bégin, Saint-Mandé, France; GINECO and Regional Centre Control Against Cancer Francois Baclesse, Caen, France; Gustave roussy, Villejuif, France; Gustave Roussy, Villejuif, France View Less
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA