This study is conducted in accordance with the Declaration of Helsinki, international ethical and good clinical practice guidelines, and local laws and regulations, with institutional review board/ethics committee approval at each site and written informed consent from patients before participation. This trial is registered with EudraCT: 2019-000476-42. Participants must be ≥18 years old, with an Eastern Cooperative Oncology Group performance status of 0 or 1. Additionally, patients must have mCRPC that progressed on/after ≥3 months of NAH for mHSPC or mCRPC and ≥2 cycles of docetaxel unless they refused or were ineligible, with ≥2 bone metastases on bone scan, no visceral metastases, and a worst pain score ≥1 on the Brief Pain Inventory-Short Form. Patients are randomized 1:1 to radium-223 or NAH:
- Radium-223 will be given as 55 kBq/kg intravenously every 4 weeks for 6 cycles or until disease progression, death, or withdrawal of consent if earlier, or
- Abiraterone 1000 mg + prednisone 10 mg daily (if prior enzalutamide), or
- Enzalutamide 160 mg daily (if prior abiraterone) until disease progression, death, or withdrawal of consent
The study schema for the RADIANT trial is as follows:
NAH dosing may be modified to manage adverse events. Patients must use luteinizing hormone-releasing hormone analogs, if not surgically castrated, and bone health agents (bisphosphonates or denosumab) throughout the study. The primary endpoint is OS, and secondary endpoints are time to first symptomatic skeletal event, radiologic progression-free survival, time to pain progression, adverse events, fracture incidence, and time to deterioration in quality of life (FACT-P total score). Using a test with a two-sided alpha of 0.05, 90% power, and randomization ratio of 1:1, approximately 508 events are required to detect a 33% increase in OS with radium-223 vs NAH, assuming a median OS of 10 months with NAH.
The study is expected to randomize 696 patients and is currently recruiting patients at 42 of the 133 planned study sites in Asia, Australia, and Europe (including Israel). The first patient was enrolled on November 9, 2020, and to date, 39 patients have been screened and 18 have been randomized. The expected study duration is 4.6 years and results are anticipated in 2024.
Clinical trial information: 2019-000476-42.
Presented by: Karim Fizazi, MD, PhD, Institut Gustave Roussy and University of Paris Saclay, Villejuif, France
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
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