(UroToday.com) The 2023 GU ASCO annual meeting included a session on trials in progress for prostate cancer, featuring a presentation by Dr. Bridget Koontz discussing the trial design of NRG-GU011, a phase II double-blinded, placebo-controlled trial of prostate oligometastatic radiotherapy with or without androgen deprivation therapy in oligometastatic prostate cancer.
There is no clear standard of care for biochemically recurrent prostate cancer with PET-detected oligometastases and normal conventional imaging. Phase II trials show that stereotactic ablative body radiotherapy (SABR) to oligometastases may delay cancer progression and initiation of ADT and its untoward effects. ADT with radiation prolongs survival in locally advanced prostate cancer and in conventionally imaged metastatic prostate cancer. However, there is a knowledge gap about timing and benefit vs toxicity of ADT with SABR in early oligometastatic prostate cancer. NRG GU011 (PROMETHEAN) is a randomized phase II trial of SABR with or without relugolix for early PET-detected recurrent oligometastatic prostate cancer. This study aims to evaluate the impact of relugolix, a novel oral gonadotropin-releasing hormone receptor antagonist, when combined with SABR to oligometastases. Relugolix allows for rapid testosterone recovery and is associated with fewer cardiovascular events when compared to leuprolide and is hypothesized to have low late ADT toxicity. GU011 will provide patients and their physicians data on the relative risks and benefits of early or delayed ADT in this setting.
NRG-GU011 NCT05053152 is a randomized phase II double-blinded, placebo-controlled trial with randomization to SABR + 6 months placebo vs SABR + 6 months relugolix. The trial design for NRG-GU011 is as follows:
Eligible patients have biochemical recurrence after prior curative intent radiation or surgery for localized prostate cancer, PSA < 10 ng/mL, negative conventional imaging and 1-5 PET-evident metastases (≥1 extrapelvic). SABR is delivered in 1-5 fractions to BED >100 Gy1.5, followed by placebo or relugolix 120mg daily for 6 months. Patients will then be followed with imaging at time of biochemical recurrence. The planned sample size of 260 patients (130 per arm) will provide 85% power to detect a hazard ratio of 0.65 for radiographic progression-free survival, based on a one-sided test at alpha 0.10. Planned enrollment is predicted at 8 patients per month with an estimated study completion date of late 2026. The primary endpoint is conventional imaging radiographic progression-free survival. Secondary endpoints include:
- PET-based radiographic progression-free survival
- Sexual and hormonal quality of life (QoL) assessed by EPIC-26
- Other QoL measures from EQ5D-5L, EORTC QLQ-30 and PROMIS Fatigue
- Between-group comparisons of time to salvage therapy, castration-resistance, local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival
Dr. Koontz and colleagues also aim to determine adverse event rates for both treatment arms and evaluate genomic and blood markers of treatment response. This study opened in December 2021.
Clinical Trial Information: NCT05053152
Co-Authors: Theodore Karrison, Thomas Michael Pisansky, Edwin Melencio Posadas, Leslie K. Ballas, Alejandro Berlin, William A. Hall, Phuoc T. Tran, Jennifer C O'Daniel, Thomas A. Hope, Joseph P. Rodgers, Felix Y Feng
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.