BRIDGES: A phase 3 randomized trial of immediate postoperative cesium-131 tile-based radiation therapy followed by abbreviated chemoradiation for newly diagnosed glioblastoma (NCT07195591).

Abstract

TPS2105 Background: Glioblastoma remains a lethal primary brain tumor with limited therapeutic progress and a persistent unmet clinical need. Standard management requires maximal safe resection followed by external beam radiation therapy (EBRT) with concurrent temozolomide (TMZ); however, the required 4–6-week postoperative healing interval before initiating EBRT creates a vulnerable window for rapid early progression (REP), defined as radiographic tumor progression occurring between surgery and the start of chemoradiation. REP is detected in more than half of patients and is associated with inferior survival. Tile-based radiation therapy (TBRT) with cesium-131 brachytherapy sources (GammaTile, GT Medical Technologies, Tempe, AZ, USA), offers a strategy to eliminate this treatment gap by immediately initialing localized radiation at the time of resection. A feasibility and safety study (NCT05342883) evaluating TBRT implantation following EBRT has been fully accrued and supports randomized evaluation. The BRIDGES study (NCT07195591) builds on this foundation. Methods: NCT07195591 is a prospective, randomized, open-label, multicenter, phase 3 trial to evaluate whether immediate postoperative TBRT followed by abbreviated EBRT with concurrent and adjuvant TMZ improves outcomes compared with standard postoperative EBRT with concurrent and adjuvant TMZ. Eligible adults must have newly diagnosed, radiographic suspicion of glioblastoma, can undergo maximal safe resection, possess a Karnofsky Performance Status score ≥70, and be candidates for standard chemoradiation. Key exclusion criteria include multifocal or disseminated disease, prior cranial radiation or chemotherapy, inability to receive TMZ, and medical comorbidities that would interfere with protocol treatment or follow-up. Patients are randomized 2:1 to receive either TBRT implantation followed by a shortened EBRT course with concurrent and adjuvant TMZ or standard postoperative EBRT with concurrent and adjuvant TMZ. Randomization is stratified by age, sex, prior sub-maximal safe resection, and size of pre-operative tumor. A stratified log-rank test using Kaplan–Meier methods will be done using the stratification factors will be implemented for the primary endpoint. Additional time-to-event endpoints will be analyzed using Kaplan–Meier methods and Cox proportional hazards models, and the analyses will follow the intent-to-treat principle. The trial has two pre-planned interim analyses. A Data and Safety Monitoring Board will oversee the trial and conduct periodic safety reviews. Four of the 766 planned patients have enrolled. Clinical trial information: NCT07195591 .