Tessa Jowell BRAIN MATRIX - Platform Study (BRAIN MATRIX)

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

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 United Kingdom, 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.

Study Overview

• Status: Recruiting
• Conditions: Glioma
• Intervention / Treatment: Other: Matched Tumour and Blood Sample - Research Pathway; Other: Matched Tumour and Blood Sample - NHS GMS pathway

Detailed Description

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.

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.

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Rhys Mant; Phone Number: 0121 414 6788; Email: brainmatrix@trials.bham.ac.uk
• Study Contact Backup: Name: Joshua Savage; Email: j.savage.1@bham.ac.uk

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Recruiting
    • Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Foundation Trust
    • Principal Investigator: Victoria Wykes
  • Cambridge, United Kingdom, CB2 0QQ
    • Active, not recruiting
    • Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • NHS Lothian
    • Principal Investigator: Paul Brennan
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Queen Elizabeth Unviersity Hospital, NHS Greater Glasgow and Clyde Health Board
    • Principal Investigator: Anthony Chalmers
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James' University Hospital, Leeds Teaching Hospitals NHS Trust
    • Principal Investigator: Susan Short
  • Liverpool, United Kingdom, L9 7LJ
    • Recruiting
    • Walton Centre, Walton Centre NHS Foundation Trust
    • Principal Investigator: Michael Jenkinson
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital, Kings College Hospital NHS Foundation Trust
    • Principal Investigator: Keyoumars Ashkan
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie Hospital, The Christie NHS Foundation Trust
    • Principal Investigator: Catherine McBain
  • Manchester, United Kingdom, M6 8HD
    • Recruiting
    • Salford Royal Hospital, Salford Royal NHS Foundation Trust
    • Principal Investigator: David Coope
  • Newcastle Upon Tyne, United Kingdom, j.savage.1@bham.ac.uk
    • Recruiting
    • Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust
    • Principal Investigator: Joanne Lewis
  • Nottingham, United Kingdom, NG7 2UH
    • Recruiting
    • Queens Medical Centre, Nottingham University Hospitals NHS Trust
    • Principal Investigator: Stuart Smith
  • Oxford, United Kingdom, OX3 9DU
    • Not yet recruiting
    • John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
    • Principal Investigator: Olaf Ansorge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

• Newly diagnosed suspected WHO Grade 2-4 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 WHO Grade 2-4 glioma (those with available frozen tumour will be prioritised for detailed genomic analysis).
• Valid written informed consent for the study.

Exclusion Criteria:

• Primary spinal cord tumours
• Active treatment of other malignancy
• Contraindication to MRI
• Patients without standard of care imaging available

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (from biopsy) to integrated histological-molecular diagnosis	This is defined as the difference (days) between date of biopsy and date of whole genome diagnosis and epigenomic classification.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to completion of each node of tissue and imaging pathway	The time to each node of the pathway will be measured from the date of receipt at the current node to date of delivery at the next.	To be achieved within a timescale of up to 5 years
Tumour and biological sample(s) quality control status	Tumour and biological sample collection will be measured against protocol guidelines. These data will be collected in the surgical and pathological forms.	To be achieved within a timescale of up to 5 years
Imaging quality control status	Imaging will be measured against established clinical guideline. The imaging form will measure compliance against these guidelines.	To be achieved within a timescale of up to 5 years
Inter-rater agreement of Response Assessment in Neuro-Oncology (RANO)	Scans will be assessed and scored according to RANO criteria by the hub of Neuro-radiologists.	To be achieved within a timescale of up to 5 years
Extent of surgical resection	Evaluated from the post-operative MRI scan and categorised as follows: Closed biopsy, open biopsy, debulking <50%, subtotal resection 50-90%, near total resection 90-<100%, gross total resection 100%.	To be achieved within a timescale of up to 5 years
Overall survival time	Defined as the time from date of diagnosis to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen in clinic.	To be achieved within a timescale of up to 5 years
Intracranial progression-free survival time	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 at the time of analysis will be censored at the date last seen in clinic.	To be achieved within a timescale of up to 5 years
Quality of Life (QoL) scores	Longitudinal measures of QoL will be generated from the QoL questionnaire according to the questionnaire-specific algorithm for scoring.	To be achieved within a timescale of up to 5 years
Type of interventions received	Details of the type of interventions received will be monitored throughout the follow-up period and recorded on the Case Report Form.	To be achieved within a timescale of up to 5 years
Type of complications from treatments (standard of care) received.	Details of complications relating to standard of care treatments received will be monitored throughout the follow-up period and recorded on the Case Report Form.	To be achieved within a timescale of up to 5 years
Concordance of diagnoses	In relation to initial local radiological diagnosis, local pathological diagnosis and integrated histological-molecular diagnosis, any difference between the tiers of diagnoses will be highlighted and categorised as: discordant; agreed; refined.	To be achieved within a timescale of up to 5 years
Samples and images centrally stored	Defined as confirmed central storage of images and material.	To be achieved within a timescale of up to 5 years
Targetable mutation(s) identified	Relevant targetable mutations identified by Whole Genome Sequencing and Epigenomic Classification.	To be achieved within a timescale of up to 5 years
Post-mortem sampling consent status and sample collection confirmation	Based on receipt of post-mortem consent form, and on post-mortem samples with confirmed central storage.	To be achieved within a timescale of up to 5 years
Number of applications to, and outputs resulting from data repository	As per title.	To be achieved within a timescale of up to 5 years

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: University of Oxford; University of Edinburgh; The Brain Tumour Charity; Genomics England
• Investigators: Principal Investigator: Colin Watts, Unviersity of Birmingham

Publications and helpful links

General Publications

• Watts C, Savage J, Patel A, Mant R, Wykes V, Pohl U, Bulbeck H, Apps J, Sharpe R, Thompson G, Waldman AD, Ansorge O, Billingham L; TJBM Investigators. Protocol for the Tessa Jowell BRAIN MATRIX Platform Study. BMJ Open. 2022 Sep 8;12(9):e067123. doi: 10.1136/bmjopen-2022-067123.

Helpful Links

• Trial Website

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: RG_18-258; 14218060 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Scientifically sound proposals from appropriately qualified researchers will be considered for data sharing. Requests should be made by returning a Data Sharing Request Form to newbusiness@trials.bham.ac.uk; this captures the research requirements, statistical analysis plan, and intended publication schedule. Requests will be reviewed by the Cancer Research UK Clinical Trials Unit (CRCTU) Directors in discussion with the Chief Investigator (CI), Study Management Group (SMG) and independent Scientific Advisory Board (SAB). They will consider the scientific validity of the request, qualifications of the researchers, CI, SMG & SAB views, consent arrangements, practicality of anonymizing the requested data & contractual obligations. If supportive of the request, and where not already obtained, Sponsor consent for data transfer will be sought before notifying applicants of the outcome. It is anticipated that applicants will be notified within 3 months of receipt of the original request.
• IPD Sharing Time Frame: Data will be available within 1 year of study closure, if not before.
• IPD Sharing Access Criteria: See Plan Description above.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No