Tessa Jowell BRAIN MATRIX - Platform Study

Plain English Summary

Background and study aims
Gliomas, a type of brain tumour, are the most common primary tumour of the central nervous system (CNS) and in 2016 there were 5250 deaths from brain tumours in the UK. However, brain tumours are a challenging disease to treat. The tumour’s location within the brain and its tendency to grow into nearby brain tissue often make it very difficult to remove the tumour completely with surgery. There is also difficulty in delivering drugs in adequate amounts to the tumour due to the natural defences of the brain.
Brain tumours arise due to changes in the DNA and other molecules in cells of the brain. Different types of gliomas can have different changes and these can be used to determine a precise ‘molecular diagnosis’. The ultimate goal for the Tessa Jowell BRAIN MATRIX is to learn how to use these molecular changes to more precisely determine what exact type of tumour patients have, and to identify, decide and test whether specific ‘targeted’ treatments could improve the survival and/or quality of life of patients with brain tumours.
The Tessa Jowell BRAIN MATRIX is a programme of work, the principal purpose of which is to improve the knowledge of, and treatment for, glioma. The programme will include a Platform Study and subsequent interventional clinical trials. The Tessa Jowell BRAIN MATRIX Platform Study forms the backbone of this programme. In the Platform Study, the aim is to develop the infrastructure to provide rapid and accurate molecular diagnosis and the infrastructure to deliver clinical trials of new therapies in the future, thereby improving clinical outcomes in brain tumours.
The researchers aim to recruit 1,000 patients to the study. As gliomas occur at all ages and their specific subtype is hard to predict pre-operatively, the patient population eligible for the study is broad. A large network of clinical hubs across the UK, with expertise in managing patients with brain tumours, will be developed. Once established this infrastructure will facilitate the rapid introduction of clinical trials testing targeted therapies tailored to the genetic changes of an individual’s tumour.

Who can participate?
Any patient aged over 16 with newly diagnosed suspected glioma, (as evidenced radiologically) AND suitable for a diagnostic or therapeutic surgical procedure resulting in a tumour sample matched to a blood sample. Patients with progression with known Grade 2-4 glioma (those with available frozen tumour) will be prioritised for detailed genomic analysis.

What does the study involve?
Eligible patients will either have had, or be about to have, surgery for their tumour. As part of this study, tumour removed during the operation will be analysed to look for specific molecular changes. As with normal standard care, the tumour will be analysed by a local pathologist. A small part will be sent for review by experts and advanced molecular analysis will be undertaken to get a detailed understanding of the DNA/molecular changes within the patient’s tumour. These results will be fed back to the patient’s treating doctor. It is intended that this will occur within 28 days; however, it may be longer while the study becomes fully operational. If samples are available from a patient’s previous surgery to their tumour, these may also be analysed. Similarly, if available, other relevant samples such as cerebrospinal fluid, collected as part of their care, may also be analysed. In addition, as technologies and analyses improve the understanding of brain tumours, the researchers may find important results at a later date. These will be fed back to the patient’s doctor. Patients will also be asked to give a blood sample, which will also be analysed to look at the molecular features, including of their DNA. This is required to identify what ‘new’ changes have occurred in the patient’s tumour. Following surgery, patients will continue with other treatment(s) as directed by their doctor. Treatment generally involves radiotherapy and chemotherapy. As is standard practice, patients will be closely monitored for signs of disease progression and the effects of the treatment given. As part of this study, information on patients’ treatments and disease will be collected. Images from brain scans patients undergo, along with relevant clinical information, will also be sent to and stored by the University of Edinburgh, and where appropriate, undergo expert review by a panel of radiologists with expertise in brain tumours. If patients have further surgery, some of the tissue removed may also be analysed.

What are the possible benefits and risks of participating?
The researchers want to try and improve the outcome for patients with glioma and believe that providing this standardised platform may improve outcomes in, and options for, patients. However, it is possible that this may not show any benefit over the current UK standard practice.

Where is the study run from?
Cancer Research UK Clinical Trials Unit, University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
October 2018 to March 2026

Who is funding the study?
The Brain Tumour Charity (UK)

Who is the main contact?
Mr Rhys Mant
brainmatrix@trials.bham.ac.uk

Trial website

https://www.birmingham.ac.uk/brainmatrix

Type

Scientific

Primary contact

Mr Rhys Mant

ORCID ID

Contact details

BRAIN MATRIX Study Office
Cancer Research UK Clinical Trials Unit
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 6788
brainmatrix@trials.bham.ac.uk

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 44006, IRAS 269228

Scientific title

A British feasibility study of molecular stratification and targeted therapy to optimize the clinical management of patients with glioma by enhancing clinical outcomes, Reducing avoidable toxicity, improving management of post-operative residual & recurrent disease and improving survivorship - Platform Study

Acronym

Study hypothesis

The main aim of the Tessa Jowell BRAIN MATRIX – Platform Study is to more precisely determine the exact type of tumour patients have by developing the essential infrastructure to provide rapid and accurate molecular diagnosis. A large network of clinical hubs across the UK, with expertise in managing patients with brain tumours, will be developed. Once established this infrastructure will facilitate the rapid introduction of clinical trials testing targeted therapies tailored to the genetic changes of an individual’s tumour.

Ethics approval

Approval pending, West Midlands – Edgbaston REC (Email: NRESCommittee.WestMidlands-Edgbaston@nhs.net), REC ref: WM/19/0369

Study design

Observational; Design type: Genetic epidemiology

Primary study design

Observational

Secondary study design

Epidemiological study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Glioma

Intervention

For patient’s undergoing surgery, fresh tissue will be collected from the patient’s initial surgery and frozen until shipment to the Oxford BRAIN MATRIX Lab. Matched blood sample for germline DNA will be taken following entry into the Platform study.

Patients who are not undergoing surgery and have available tumour samples from previous tumour surgery, blood will be collected and submitted to the Oxford BRAIN MATRIX Lab along with their tumour samples.

Blood taken at Platform entry and frozen tissue taken at first surgery will be shipped together to the Oxford BRAIN MATRIX Lab for molecular analysis, as follows:
1. Whole Genome Sequencing
2. EPIC array

The BRAIN MATRIX neuropathology and genomics team will generate an integrated report (histology, Whole Genome Sequencing, Heidelberg Classifier) for each case in consultation with the local neuropathology team. When this data is available, the BRAIN MATRIX neuropathology and genomics team will conduct a virtual MDT with the local referring site to ensure all relevant information will be incorporated in the final BRAIN MATRIX diagnostic report. The resulting integrated histological-molecular report will be available to local sites.

Pseudoanonymised MRI for each patient will be collected and stored at a central imaging hub overseen by the Edinburgh Imaging Hub. Disease response assessment will be performed and additional analysis undertaken within permitted parameters.

Data will be collected on patients for up to 5 years from entry to the Platform Study where possible.

Intervention type

Genetic

Phase

Drug names

Primary outcome measure

Time (from biopsy) to integrated histological – molecular diagnosis (TTMD), defined as the difference (days) between dates of biopsy and whole genome diagnosis and epigenomic classification, measured within 28 days.

Secondary outcome measures

Secondary outcome measures to be achieved within a timescale of up to 5 years:
1. Time to completion of each node of tissue and imaging pathway, measured from the date of receipt at the current node to delivery at the next
2, Tumour and biological sample(s) QC status: tumour and biological sample collection will be measured against protocol guidelines. These data will be collected in the surgical and pathological forms.
3. Imaging QC status: imaging will be measured against established clinical guideline. The imaging form will measure compliance against these guidelines.
4. Inter-rater agreement of RANO assessments: scans will be assessed and scored according to RANO criteria by the hub of Neuro-radiologists (see imaging protocol).

Patient-centred outcome measures to be achieved within a timescale of up to 5 years::
1. Extent of surgical resection calculated as follows:
Volume removed = initial volume before surgery – residual volume after surgery (based on imaging obtained within 72 hours of surgery)
2. Overall survival time, defined as the time from date of diagnosis to the date of death. Surviving patients will be censored at the date last seen in clinic
3. Intracranial progression-free survival, defined as the time from date of registration to the earliest of date of Intracranial progressive disease or death from disease. The date of an event is defined as the earliest confirmation of progression by radiological assessment, clinical symptoms or MDT. Patients without progression will be censored at the date last seen in clinic.
4. Quality of life: longitudinal QoL data will be scored according to the questionnaire-specific algorithm.
5. Type of interventions received (e.g. surgical wound infection) monitored throughout the follow-up period and recorded on the CRF
6. Type of complications from treatments (standard of care) received (e.g. surgical wound infection) monitored throughout the follow-up period and recorded on the CRF
7. Concordance of diagnoses: any difference between the tiers of diagnoses will be highlighted and categorised as: discordant; agreed; refined

Research framework outcome measures to be achieved within a timescale of up to 5 years::
1. Samples and images centrally stored
2. Targetable mutation(s) identified by WGS and EC
3. Post-mortem sampling consent status and sample collection confirmation, based on receipt of PM consent form, and on PM samples with confirmed central storage.
4. Number of applications to, and outputs resulting from data repository

Overall trial start date

01/10/2018

Overall trial end date

01/03/2026

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Newly diagnosed suspected glioma, (as evidenced radiologically) AND suitable for a diagnostic or therapeutic surgical procedure resulting in a tumour sample matched to a blood sample
2. Patients with progression with known Grade 2-4 glioma (those with available frozen tumour will be prioritised for detailed genomic analysis)
3. Valid written informed consent for the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1000; UK Sample Size: 1000

Participant exclusion criteria

1. Primary spinal cord tumours
2. Active treatment of other malignancy
3. Contraindication to MRI

Recruitment start date

01/03/2020

Recruitment end date

01/03/2025

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham (lead centre)
University Hospital Birmingham NHS Foundation Trust Mindelsohn Way Edgbaston
Birmingham
B15 2WB
United Kingdom

Trial participating centre

Addenbrooke’s Hospital
Cambridge University Hospitals NHS Foundation Trust Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Western General Hospital
NHS Lothian Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh
NHS Lothian 51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Queen Elizabeth Univeristy Hospital
NHS Greater Glasgow and Clyde Health Board 1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Trial participating centre

St James's Unviersity Hospital
Leeds Teaching Hospitals NHS Trust Beckett St
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Walton Centre
Walton Centre NHS Foundation Trust Lower Lane Fazakerley
Liverpool
L9 7LJ
United Kingdom

Trial participating centre

Kings College Hospital
Kings College Hospital NHS Foundation Trust Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Salford Royal Hospital
Salford Royal NHS Foundation Trust Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

The Christie
The Christie NHS Foundation Trust Wilmslow Road
Manchester
M20 4BX
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham University Hospitals NHS Trust Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

John Radcliffe Hospital Oxford University Hospitals NHSFT
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Organisation

University of Birmingham

Sponsor details

Research Support Group
Aston Webb Building (B Block)
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8011
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

http://www.birmingham.ac.uk/index.aspx

Funder type

Charity

Funder name

Brain Tumour Charity

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

1. Peer-reviewed scientific journals
2. Internal report
3. Conference presentation
4. Publication on website
5. Other publication

IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Intention to publish date

01/03/2027

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

13/01/2020: Trial's existence confirmed by the NIHR.