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ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma
Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for glioblastoma. In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of patients with newly diagnosed GBM(ndGBM) without...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699074/ http://dx.doi.org/10.1093/noajnl/vdaa143.011 |
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author | Nakada, Mitsutoshi |
author_facet | Nakada, Mitsutoshi |
author_sort | Nakada, Mitsutoshi |
collection | PubMed |
description | Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for glioblastoma. In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of patients with newly diagnosed GBM(ndGBM) without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. 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 concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. Methods: TRIDENT is an international phase III randomized trial comparing standard RT/TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 kHz) will be delivered over18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, over 18 years old, KPS over 70, either sex, post-surgery or biopsy, and amenable 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: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS2, PFS6, PFS12); 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 lower than 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. |
format | Online Article Text |
id | pubmed-7699074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-76990742020-12-02 ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma Nakada, Mitsutoshi Neurooncol Adv Supplement Abstracts Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for glioblastoma. In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of patients with newly diagnosed GBM(ndGBM) without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. 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 concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. Methods: TRIDENT is an international phase III randomized trial comparing standard RT/TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 kHz) will be delivered over18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, over 18 years old, KPS over 70, either sex, post-surgery or biopsy, and amenable 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: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS2, PFS6, PFS12); 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 lower than 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. Oxford University Press 2020-11-28 /pmc/articles/PMC7699074/ http://dx.doi.org/10.1093/noajnl/vdaa143.011 Text en © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Supplement Abstracts Nakada, Mitsutoshi ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title | ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title_full | ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title_fullStr | ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title_full_unstemmed | ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title_short | ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma |
title_sort | es-2 phase 3 trident trial: radiation and temozolomide with or without tumor treating fields in newly diagnosed glioblastoma |
topic | Supplement Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699074/ http://dx.doi.org/10.1093/noajnl/vdaa143.011 |
work_keys_str_mv | AT nakadamitsutoshi es2phase3tridenttrialradiationandtemozolomidewithorwithouttumortreatingfieldsinnewlydiagnosedglioblastoma |