Protocol for the Tessa Jowell BRAIN MATRIX Platform Study

Abstract

Introduction: Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK National Health Service resources to support research that is patient centric and attractive to both academic and commercial investors.

Methods and analysis: The TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for patients with glioma. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in patients with glioma from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological-molecular diagnosis using whole-genome sequencing and epigenomic classification. Secondary outcome measures include those that are process centred, patient centred and framework based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients.

Ethics and dissemination: The study will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland and stated in the respective participating countries' laws governing human research, and Good Clinical Practice. The protocol was initially approved on 18 February 2020 by West Midlands - Edgbaston Research Ethics Committee; the current protocol (v3.0) was approved on 15 June 2022. Participants will be required to provide written informed consent. A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The results of this study will be disseminated through national and international presentations and peer-reviewed publications. Manuscripts will be prepared by the Study Management Group and authorship will be determined by mutual agreement.

Trial registration number: NCT04274283, 18-Feb-2020; ISRCTN14218060, 03-Feb-2020.

Keywords: clinical trials; neurological oncology; neurosurgery.

Figure 1

Overview of the Tessa Jowell BRAIN MATRIX Programme. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study will collect and integrate clinical, pathological, advanced molecular, imaging, quality of life, treatment and outcome data. The platform may provide data directly or support identification of eligible patients to clinical trials, within and outside the TJBM study programme. If eligible, patients may be enrolled in multiple add-on studies. Through consent and with strong governance processes, anonymised or pseudonymised data may be shared with other relevant organisations or studies within and outside the programme. GEL, Genomics England; NHS, National Health Service.

Figure 2

Study schema for the Tessa Jowell BRAIN MATRIX Platform study. GLH, Genomic Laboratory Hub; WGS, whole-genome sequencing.

Figure 3

Sample and data flow pathways within the Tessa Jowell BRAIN MATRIX Platform (TJBM) study. *TJBM sites in England are encouraged to route all samples through their local NHS GMS GLH; however, if this pathway is not yet activated or GEL consent cannot be obtained, the TJBM Study Office can facilitate the processing of samples through an alternative NHS GMS GLH or via the GEL Research pathway. GEL, Genomics England; GLH, Genomic Laboratory Hub; GMS, Genomic Medicine Service; GTAB, Genomics Tumour Advisory Board; NHS, National Health Service; WGS, whole-genome sequencing.