A randomized, non-comparative, phase II multicentric trial on short-term darolutamide (ODM-201) concomitant to radiation therapy for patients with unfavorable intermediate-risk prostate cancer: DARIUS (AFU-GETUG P15).
Authors: Roubaud Guilhem , Bellera Carine A. , Sellan-Albert Sabrina , Cabart Mathilde , Teyssonneau Diego , Vuong Nam-Son , Poignie Ludivine , Benziane-Ouaritini Nicolas , Sargos Paul 
Published: January 2024

TPS349 Background: Androgen Deprivation Therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients (pts) with unfavorable intermediate-risk prostate cancer (Pca). However, ADT generates side effects with 30% decrease of quality of life (QoL). Enzalutamide (E) and Darolutamide (D) combined with ADT offer an overall survival benefit in advanced Pca. Without ADT, E avoid most of the deleterious effects of ADT. In a population of pts with intermediate risk Pca, 92% achieved PSA values < 0.1 ng/ml at the end of a treatment with EBRT and E alone.1 In pre-clinical models treated with D alone, testosterone (T) level remained normal.2 Such side effects related to T loss and to peripheral aromatization of T might be decreased with D alone. We assume that a combination of D given 6 months with EBRT in the treatment of unfavorable intermediate risk Pca is efficient and safe, without consequences on QoL. Methods: DARIUS is a national, multi-center, non-comparative randomized phase II prospective study (NCT05346848). The primary objective is to assess antitumor activity of D given 6 months with EBRT in pts with unfavorable intermediate risk Pca, using a biological response defined as PSA ≤0.1ng/ml, 6 months after randomization. D 6 months + EBRT and ADT 6 months + EBRT are offered in experimental and standard arm respectively. Randomization is 2:1. Regarding the experimental arm, given that E used alone achieved a 49% 6-month biological response rate in a hormone-sensible Pca pts,3 the association D + EBRT will be considered useful if it can increase this rate to at least 70%. Using a single-stage design, standard response rate (P0) is 50% and alternative hypothesis P1 is 70% (one-sided 5% type I error rate, 80% power). Following one-stage A’Hern design, 37 and 19 pts are required in the experimental and standard arm, respectively. Adding 10% of non-eligible/assessable pts, the total number is 62. Enrollment have already begun and 5 pts have been enrolled. Inclusion criteria are: PS ECOG ≤ 2; histological diagnosis of Pca, without metastasis (on Pelvic MRI AND thoraco-abdomino-pelvic contrast-enhanced CT-Scan AND Bone Scintigraphy); with unfavorable intermediate risk Pca diagnosis (NCCN Guidelines): 1- either Gleason = 7 (4+3) OR, 2- ≥ 50% of the core of biopsies positive for adenocarcinoma OR, 3- two or three of the following criteria (PSA value between 10-20 ng/ml, Gleason 7 (3+4) or 6, T2b (clinical or radiological)). Pts with T3a extension on MRI can be included if Gleason score is 6 and PSA < 20. Secondary objectives are biochemical Progression Free Survival, MFS, DFS, Pca-specific survival, Time to T recovery, safety, QoL and bone mineral density. Predictive factors will be investigated using Radiomics and DECIPHER. 1. Lara Front Oncol 2022. 2. Molainen Sci Rep 2015. 3. Tombal Lancet Oncol 2014. Clinical trial information: NCT05346848 .