Multi-Arm GlioblastoMa Australasia (MAGMA): protocol for a multiarm randomised clinical trial for people affected by glioblastoma

Abstract

Introduction: Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) 'neoadjuvant' chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform.

Methods and analysis: MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023.Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment.The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive/prognostic biomarkers and health utilities and incremental cost-effectiveness ratio.The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention.

Ethics and dissemination: The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

Trial registration number: ACTRN12620000048987.

Keywords: Adult oncology; Magnetic resonance imaging; Neurological oncology.

Figure 1

Comparison of median OS in retrospective studies of prolonged (>6 months) adjuvant phase temozolomide (adapted from published data33 34). OS, overall survival.

Figure 2

The International Committee of Medical Journal Editors (ICJME) criteria for authorship can be authentically met by most if not all healthcare professionals contributing to clinical trial conduct, as they can be shown to have met the contributions outlined above. An example of a consortium model for research is found in the multiarm, multistage STAMPEDE trial for prostate cancer.

Figure 3

MAGMA study schema showing randomisation for the initial two interventions: (1) early postoperative temozolomide (TMZ) versus standard chemoradiotherapy (2) extended vs 6 months adjuvant TMZ. Treatment allocation to each intervention will be balanced (1:1) using minimisation over several clinically important stratification factors (listed in box 2). MAGMA, Multi-Arm GlioblastoMa Australasia.