Intergroup study EORTC-1532-gucg: A phase 2 randomized open-label study of oral darolutamide (ODM-201) vs. androgen deprivation therapy (ADT) with LHRH agonists or antagonist in men with hormone naive prostate cancer (PCa).

Abstract

TPS406 Background: Androgen deprivation therapy (ADT) by LHRH analogues aims to lower serum testosterone. ADT is associated with several side effects that include hot flushes, depression, loss of libido, metabolic disturbances leading to an increase risk of cardiovascular disease, increased bone resorption leading to increased risk of osteoporosis and skeletal fracture. AR antagonists may circumvent these side effects by suppressing AR transcription by competitive inhibition of AR, without lowering systemic testosterone. In Europe, first generation AR antagonists bicalutamide 150 mg is registered for the treatment of non-metastatic hormone-naïve PCa. is a novel AR antagonist that is structurally distinct with higher AR-binding affinity compared to bicalutamide, enzalutamide, and apalutamide. The aim of this trial is to investigate the activity, safety and tolerability of darolutamide as single agent, as an alternative to LHRH analogues in men requiring ADT. Methods: EORTC-1532-GUCG (NCT02972060) will randomize 250 men with hormone-naïve PCa 1:1 to 600 mg (2× 300-mg tablets) bid of darolutamide1 or LHRH agonist or antagonist, stratified for type of ADT (agonist vs. antagonist), disease extent (measurable, non-measurable, vs. no metastasis) and age (≥70 vs < 70 years). Key inclusion criteria include histologically confirmed asymptomatic PCa (all stages) for whom continuous ADT is indicated for a minimum period of 24 weeks. Patients with up to 4 confirmed not visceral metastases, are allowed. Baseline total testosterone should be ≥ 8 nmol/L or 230 ng/dL. Primary endpoint is PSA response assessed at 24 weeks, defined as a ≥ 80% decline in PSA at week 24 in the darolutamide study arm. The ADT arm is used as an internal non comparative control. Key secondary endpoints include: Change in hormone-treatment related symptoms scale of the EORTC QLQ-PR25 at 24 weeks (comparison between arms); objective response rate at 24 weeks in patients with measurable disease at baseline, safety according to NCI-CTC version 4.0. Clinical trial information: NCT02972060.