Abstract CT258: EF-32 (TRIDENT): A pivotal randomized trial of radiation therapy concomitant with temozolomide +/- Tumor Treating Fields (TTFields) in newly diagnosed glioblastoma
Authors: Shi Wenyin , Kleinberg Lawrence , Jeyapalan Suriya A. , Goldlust Samuel A. , Nagpal Seema , Combs Stephanie E. , Roberge David , Nishigawa Ryo , Grossman Rachel , Glas Martin 
Published: July 2021

Abstract
Purpose: Tumor treating fields (TTFields) is a non-invasive, loco-regional antimitotic treatment approved as a standard-of-care for newly diagnosed glioblastoma (ndGBM). In the Phase 3 EF-14 trial, TTFields (200 kHz) plus temozolomide (TMZ) post-surgery and chemoradiation significantly increased survival of ndGBM patients compared to TMZ alone. The addition of TTFields was not associated with any increases in systemic toxicity. TTFields-related adverse events (AEs) were mainly dermatological. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of TTFields concomitant with RT and TMZ will be investigated in the TRIDENT trial. Methodology: TRIDENT (NCT04471844) is an international, pivotal randomized trial comparing standard RT with concomitant TMZ vs the triple combination of RT with concomitant TMZ and TTFields. RT is delivered through the TTFields transducer arrays. Patients in both arms will receive maintenance TTFields and TMZ. TTFields (200 KHz) will be delivered &gt;18 hours/day using the Optune device. TTFields treatment will be continued until the second disease recurrence. Patients with pathologically confirmed ndGBM, ≥ 18 years (≥ 22 years in the US), KPS ≥ 70, either sex, post-surgery or biopsy, and candidates for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points include progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), PFS (PFS6M, PF12M, PFS2Y); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR&lt; 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive. The TRIDENT trial is currently enrolling patients.
Citation Format: Wenyin Shi, Lawrence Kleinberg, Suriya A. Jeyapalan, Samuel A. Goldlust, Seema Nagpal, Stephanie E. Combs, David Roberge, Ryo Nishigawa, Rachel Grossman, Martin Glas. EF-32 (TRIDENT): A pivotal randomized trial of radiation therapy concomitant with temozolomide +/- Tumor Treating Fields (TTFields) in newly diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT258.