Dose-enhanced versus standard TTFields for first recurrence of glioblastoma: A randomized phase 2 clinical trial.

Abstract: BackgroundStudies suggest that high intensities of tumor treating fields (TTFields) correlate with prolonged survival in newly diagnosed glioblastoma. However, no randomized clinical studies have tested different doses of TTFields, and the treatment remains controversial for recurrent glioblastoma. This study examined the clinical efficacy of dose-enhanced TTFields in first recurrence glioblastoma (rGBM). Methods: This open-label, randomized, multicenter, phase 2 clinical trial was conducted nationwide in Denmark (2020-2024) with planned enrollment of 84 rGBM patients. Inclusion criteria were focal disease, KPS ≥ 70, and eligibility for resection. Patients were randomized (1:1) to receive standard or dose-enhanced TTFields in addition to standard-of-care. Dose enhancement (25%-70%) in the tumor was achieved by placing five small cranial burr holes over the tumor bed with overlapping TTFields transducer arrays. The primary outcome was the overall survival (OS) rate at 12 months (OS12). Secondary outcomes included progression-free survival, toxicity, steroid use, objective response rate (ORR), and quality of life. Results: We enrolled 58 participants with a mean (SD) age of 59.2 (11.1) years and a median (IQR) KPS of 90 (10). Preplanned interim analysis of the first 52 patients resulted in early trial termination due to futility. Intent-to-treat analysis of the complete cohort showed an OS12 of 56% vs 46% (P = .38) and a median OS of 12.3 vs 11.1 months (P = .93) for intervention and control, respectively. Differences in the secondary outcomes were insignificant. Conclusion: Dose-enhanced TTFields utilizing burr holes over the resection cavity were not associated with improved survival in rGBM, with low study power as the primary limitation.