3139 - Effectiveness of an Iodinated Perirectal Hydrogel Spacer for Prostate Cancer Treated with Stereotactic Body Radiotherapy (SBRT): A Prospective, Multi-Center, Randomized Trial ("SABRE")

P. Blanchard¹, S. P. Collins², B. Hedstrom³, E. Chaussee⁴, M. J. Zelefsky⁵, and S. Jain⁶; ¹Gustave Roussy, Villejuif, France, ²Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, ³Boston Scientific, Marlborough, MA, United States, ⁴Boston Scientific, Marlborough, MA, ⁵NYU Langone Health, New York, NY, ⁶Northern Ireland Cancer Centre, Belfast, United Kingdom

Purpose/Objective(s): Radiation therapy is one of the standard local treatments for prostate cancer. It can be associated with increased risk of acute and late toxicity, especially when the dose per fraction increases. Clinicians are seeking technologies that can reduce rectal radiation dose to help minimize the risk of rectal injury associated with radiotherapy. A proposed solution has been to increase separation between the anterior rectal wall and the prostate gland using polyethylene glycol (PEG)-based hydrogel spacing. A next generation iodinated PEG-based hydrogel adds radiopacity to allow for visibility under CT and cone beam CT. Additionally, large multi-center trials using perirectal spacing with SBRT are lacking. The main objective of this trial in progress is to demonstrate the effectiveness of the iodinated perirectal hydrogel spacer in reducing late gastrointestinal (GI) toxicity in subjects undergoing SBRT to treat prostate cancer. Materials/

Methods: This is a prospective, multi-center, multinational randomized control trial (NCT04905069). Approximately 30-35 sites in the US, UK, France, Germany, Ireland, Italy, Spain, Switzerland, and Australia have been or are expected to be authorized to enroll. 500 subjects with a diagnosis of intermediate risk prostate cancer, indicated for SBRT, will be randomized (2:1) to the iodinated perirectal hydrogel spacer treatment group (n~333) or the nospacer control group (n~167). Treatment subjects will undergo transperineal injection of 10 mL of the hydrogel. SBRT (40 Gy in 5 fractions) is planned for all subjects. Over 5-year follow-up, subjects will be assessed for GI and GU toxicity (NCI CTCAE), quality of life (EQ-5D-5L and EPIC-26 questionnaires), tumor control (PSA levels), device deficiencies and concomitant medications.

The primary endpoint is late GI toxicity (3-24 months; =Grade 2 AE) after SBRT treatment with or without placement of the hydrogel spacer. Superiority of the hydrogel spacer on the AE cumulative incidence relative to control will be evaluated using the log-rank test. The key secondary endpoint is a decrease in EPIC-26 bowel score = the minimally important difference from baseline to 24 months post-SBRT initiation.

Results: Status: Enrollment began in December 2021 and is anticipated to complete in 2025, with primary endpoint results available 24 months following the end of enrollment. Study completion (final 5-year follow up) is estimated in 2030. As of March 1, 2024, 219 subjects have been randomized.
Conclusion: This study is designed to demonstrate the clinical benefit of using iodinated perirectal hydrogel spacer for perirectal spacing in patients receiving SBRT for prostate cancer. Long-term follow-up including patient-reported outcomes is intended to provide insight into how space creation with this technology may reduce toxicity and be associated with improved quality-of-life.