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

• Published in: BMJ open Vol. 14; no. 3; p. e078926
• Main Authors: Hudson, Eleanor M, Noutch, Samantha, Webster, Joanne, Brown, Sarah R, Boele, Florien W, Al-Salihi, Omar, Baines, Helen, Bulbeck, Helen, Currie, Stuart, Fernandez, Sharon, Hughes, Jane, Lilley, John, Smith, Alexandra, Parbutt, Catherine, Slevin, Finbar, Short, Susan, Sebag-Montefiore, David, Murray, Louise
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 08.03.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Adult; Brain; Brain cancer; Brain research; Caregivers; Chemotherapy; Clinical Trials, Phase II as Topic; Consent; Glioblastoma - drug therapy; Glioblastoma - radiotherapy; Humans; Medical prognosis; Multicenter Studies as Topic; Neoplasm Recurrence, Local - drug therapy; Neurological oncology; Oncology; Patients; Quality of Life; Questionnaires; Radiation oncology; Radiation therapy; RADIOTHERAPY; Randomized Controlled Trials as Topic; Re-Irradiation; Toxicity; Tumors; United Kingdom > UK; Neurological oncology; RADIOTHERAPY; ONCOLOGY; Radiation oncology
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-078926

IntroductionGlioblastoma (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 analysisBRIOChe 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 disseminationBRIOChe 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 numberISRCTN60524.