DASL-HiCAP (ANZUP1801): The impact of darolutamide on standard therapy for localized very high-risk cancer of the prostate—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive

Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) for at least one year, is standard of care for men with very high-risk localised prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high risk features. Darolutamide is an androgen receptor antagonist with favourable tolerability. Our aim is to determine the efficacy of adding darolutamide to ADT and RT given in the setting of either primary definitive therapy (RP or RT), or adjuvant therapy for very high-risk PC.

Methods: This study is a randomised (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localised PC, or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: use of adjuvant docetaxel; pelvic nodal involvement; RP. 1100 participants will be randomised to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival, with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment.

Clinical trial information: NCT04136353

Authors: Tamim Niazi, Scott Williams, Ian D. Davis, Martin R. Stockler, Andrew James Martin, Wendy Hague, Karen Bracken, Margot Gorzeman, Felicia Roncolato, Sonia Yip, Lisa Horvath, Shomik Sengupta, Simon Hughes, Raymond S. McDermott, James WF Catto, Neha Vapiwala, Wendy R. Parulekar, Christopher Sweeney

Author Affiliations: Jewish General Hospital, McGill University, Montreal, QC, Canada; Peter MacCallum Cancer Centre, Melbourne, Australia; Monash University Eastern Health Clinical School, Melbourne, Australia; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Macarthur Cancer Therapy Centre, Sydney, Australia; Sydney Catalyst Translational Cancer Research Centre, Sydney, Australia; Sydney Cancer Centre, Sydney, Australia; Olivia Newton-John Cancer Wellness and Research Centre, Melbourne, Australia; Guy's Cancer, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; Adelaide and Meath Hospital (Incorporating the National Children's Hospital), Dublin, Ireland; Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom; University of Pennsylvania, Philadelphia, PA; Canadian Cancer Trials Group, Kingston, ON, Canada; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA

Source: Niazi T, Williams S, Davis I, et al. "DASL-HiCAP (ANZUP1801): The impact of darolutamide on standard therapy for localized very high-risk cancer of the prostate—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation in very high-risk, clinically localized prostate cancer." J Clin Oncol. Feb 19 2020. 38, no. 6_suppl
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