Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) - protocol for a multi-centre open-label randomised trial.

Hudson, EM.; Noutch, S.; Webster, J.; Brown, SR.; Boele, FW.; Al-Salihi, O.; Baines, H.; Bulbeck, H.; Currie, S.; Fernandez, S.; Hughes, J.; Lilley, J.; Smith, A.; Parbutt, C.; Slevin, F.; Short, S.; Sebag-Montefiore, D.; Murray, L.

Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) - protocol for a multi-centre open-label randomised trial.

All Authors

Hudson, EM.

Noutch, S.

Webster, J.

Brown, SR.

Boele, FW.

Al-Salihi, O.

Baines, H.

Bulbeck, H.

Currie, S.

Fernandez, S.

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LTHT Author

Currie, Stuart
Lilley, John
Parbutt, Catherine
Slevin, Finbar
Short, Susan
Murray, Louise

LTHT Department

Radiology
Medical Physics & Engineering
Leeds Cancer Centre
Medicines Management & Pharmacy Services
Oncology

Non Medic

Consultant Pharmacist

Publication Date

2024

Item Type

Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't

Abstract

INTRODUCTION: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM. METHODS AND ANALYSIS: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival. ETHICS AND DISSEMINATION: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines. TRIAL REGISTRATION NUMBER: ISRCTN60524.