Bhaskaran, D., Savage, J., Patel, A. et al. (9 more authors) (2024) A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial. BMC Cancer, 24 (1). 83. ISSN 1471-2407
Abstract
Background Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects. Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM.
Methods ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events.
Discussion Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
Keywords: | Adverse events; Brain cancer; Cannabinoids; Glioblastoma; Nabiximols; Overall survival; Progression free survival; Randomised phase II trial; Sativex; Temozolomide; Tumour |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Oncology |
Funding Information: | Funder Grant number Brain Tumour Charity Not Known Bristol Myers Squibb PRISM Cancer Research UK Supplier No: 138573 A19121 Cancer Research UK Supplier No: 138573 C7852/A19772 Cancer Research UK Supplier No: 138573 A25447 Cancer Research UK Supplier No: 138573 A23814 NHS Health Technology Assessment 09/91/21 NHS Health Technology Assessment 09/91/21 NHS Health Technology Assessment 09/91/21 Yorkshire Cancer Research Account Ref: 2UOLEEDS L387 NIHR National Inst Health Research 12/35/07 |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Jan 2024 16:04 |
Last Modified: | 25 Jan 2024 16:04 |
Published Version: | http://dx.doi.org/10.1186/s12885-023-11792-4 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Identification Number: | 10.1186/s12885-023-11792-4 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:208237 |