Abstract OT1-05-03: TRIO030: A presurgical tissue-acquisition study to evaluate molecular alterations in human breast cancer tissue following short-term exposure to the androgen receptor antagonist darolutamide
Authors: Mackey JR , Eiermann W , Fresco R , Fung H , Carrez S , Lopez C , Slamon DJ 
Published: February 2018

Abstract
Background: Endocrine treatment remains a mainstay in the treatment of patients with estrogen-receptor (ER) positive breast cancer (BC). Although ER and progesterone receptor (PgR) are well established targets with predictive and prognostic value, the clinical significance and role of the androgen receptor (AR) is poorly understood. Darolutamide is a new AR antagonist developed for the treatment of castration-resistant prostate cancer. Darolutamide potently inhibits testosterone binding to AR and retains antagonistic properties in cells expressing increased AR levels. Understanding the biological impact of AR-blockade when darolutamide targets the AR in BC should provide foundational rationale for its development in BC.
Trial Design: TRIO030 is a multi-center, open-label, tissue-acquisition study involving 60 women with early-stage invasive BC. To be able to assess the molecular alterations after darolutamide exposure in different BC subtypes, BC patients with triple-negative, or ER+/HER2 negative, or HER2 positive disease will be enrolled in the study, with 20 subjects in each group. Each participant will receive darolutamide at a dose of 600 mg b.i.d. (daily dose of 1200 mg) for a minimum duration of 14 days until the day prior to BC surgery (recommended duration of 21 days, maximum 35 days). Tumor tissue collection will include 3 pre-treatment cores (2 snap-frozen and 1 paraffin embedded) and 2 cores at surgery (1 snap-frozen and 1 paraffin embedded).
Key Eligibility Criteria: Eligible female subjects will have 1) histologically proven invasive breast carcinoma for which surgery is indicated as the primary treatment modality, 2) known ER, PgR and HER2 statuses, 3) tumor confined to either the breast or to the breast and ipsilateral axilla with T1 ≥1.5cm, T2 or T3 and either clinically positive (N1 only) or clinically negative axillary nodes (N0), and 4) no prior systemic nor local treatment for BC.
Study Objectives: The primary objective of this study is to identify the molecular changes that occur in BC tissue following short-term exposure to darolutamide in women with early BC. Secondary objectives include the safety and tolerability of short-term darolutamide in women with early BC.
Statistical Methods: Evaluability of subjects will require minimum duration of 10 consecutive days of treatment with darolutamide, tumor tissue collection at screening and at surgery and adequacy of tumor tissue samples for molecular assessment as determined by the central laboratory. Molecular analyses will be conducted on the evaluable population. Descriptive statistics will be used to compare pre and post treatment molecular findings. Correlations will be sought among molecular alterations from tumor samples collected at baseline, following administration of darolutamide, and clinicopathologic variables.
Accrual: The study will be activated in June 2017. Up to 60 evaluable subjects will be enrolled within 12 months (NCT03004534).
Citation Format: Mackey JR, Eiermann W, Fresco R, Fung H, Carrez S, Lopez C, Slamon DJ. TRIO030: A presurgical tissue-acquisition study to evaluate molecular alterations in human breast cancer tissue following short-term exposure to the androgen receptor antagonist darolutamide [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-05-03.