At the 2021 American Society of Clinical Oncology (ASCO) virtual annual meeting, Dr. Michael Morris and colleagues reviewed the trial design for a phase III study to determine the clinical benefit of docetaxel versus docetaxel and Radium-223 in patients with mCRPC, the DORA trial.
Randomization (1:1) of 738 men with mCRPC to docetaxel or docetaxel + Radium-223 is planned with a projected hazard ratio for the treatment effect (15 vs 20 months median survival) of 0.75. The trial design for DORA is as follows:
Patients with ≥2 bone lesions and progression by Prostate Cancer Working Group 3 criteria are eligible. Other key inclusion criteria are an Eastern Cooperative Oncology Group performance status of 0–1 and normal organ function. Key exclusion criteria are: (i) the use of anticancer therapy ≤4 weeks before randomization, (ii) the use of bone-seeking radiopharmaceuticals or chemotherapy in the castration-resistant setting, and (iii) bulky visceral metastases (≥3 lung and/or liver or a lesion ≥2 cm in the previous 8 weeks).
Subjects receive docetaxel 75 mg/m2 IV q3w for 10 doses or docetaxel 60 mg/m2 IV q3w for 10 doses + Radium-223 55 kBq/kg IV q6w for 6 doses. The primary endpoint is overall survival. Secondary and exploratory endpoints include:
- Radiographic progression-free survival
- Symptomatic skeletal event-free survival
- Markers of bone metabolism
- Alterations in circulating tumor cells and DNA
- Detection of androgen-receptor splice variant 7
- Changes in automated bone scan index (aBSI),
- Assessment of patient-reported outcome instruments (FACT-P, Brief Pain Inventory, Brief Fatigue Inventory)
The study is open at 32 sites in the US and Netherlands and has 170 subjects enrolled. As highlighted by the investigators, reasons to participate in this trial are as follows:
- For patients with bone metastases and CRPC, the rationale is sound in that you are treating disease systematically with docetaxel and consolidating treatment to bone metastases with radium-223. Furthermore, each arm contains life-prolonging therapy
- Most patients with mCRPC will require chemotherapy after androgen receptor targeted agents
- Prior docetaxel for mHSPC is allowed
- Many protocols require prior therapy with docetaxel for mCRPC, such as numerous arms of the KEYNOTE-365 trial assessing different pembrolizumab combinations
Clinical trial information: NCT03574571
Presented by: Michael J. Morris, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Co-Author: Ronald De Wit, Nicholas J. Vogelzang, Scott T. Tagawa, Celestia S. Higano, Paul Hamberg; Erasmus MC Cancer Institute, Rotterdam, Netherlands; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Weill Cornell Medicine, New York, NY; Fred Hutchinson Cancer Research Center, Seattle, WA; Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands
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
- Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
- Morris MJ, Loriot Y, Sweeney CJ, et al. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: A phase 1 dose escalation/randomized phase 2a trial. Eur J Cancer. 2019 Jun;114:107-116.