Clinical trial NCT04274283: Tessa Jowell BRAIN MATRIX - Platform Study
Official 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioma
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: The Brain Tumour Charity
name: University of Oxford
name: University of Edinburgh
name: Genomics England
First posted: 2020-02-18
Enrollment: 1000
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time (from biopsy) to integrated histological-molecular diagnosis
timeFrame: 28 days
Secondary outcomes:
measure: Time to completion of each node of tissue and imaging pathway
timeFrame: To be achieved within a timescale of up to 5 years
measure: Tumour and biological sample(s) quality control status
timeFrame: To be achieved within a timescale of up to 5 years
measure: Imaging quality control status
timeFrame: To be achieved within a timescale of up to 5 years
measure: Inter-rater agreement of Response Assessment in Neuro-Oncology (RANO)
timeFrame: To be achieved within a timescale of up to 5 years
measure: Extent of surgical resection
timeFrame: To be achieved within a timescale of up to 5 years
measure: Overall survival time
timeFrame: To be achieved within a timescale of up to 5 years
measure: Intracranial progression-free survival time
timeFrame: To be achieved within a timescale of up to 5 years
measure: Quality of Life (QoL) scores
timeFrame: To be achieved within a timescale of up to 5 years
measure: Type of interventions received
timeFrame: To be achieved within a timescale of up to 5 years
measure: Type of complications from treatments (standard of care) received.
timeFrame: To be achieved within a timescale of up to 5 years
measure: Concordance of diagnoses
timeFrame: To be achieved within a timescale of up to 5 years
measure: Samples and images centrally stored
timeFrame: To be achieved within a timescale of up to 5 years
measure: Targetable mutation(s) identified
timeFrame: To be achieved within a timescale of up to 5 years
measure: Post-mortem sampling consent status and sample collection confirmation
timeFrame: To be achieved within a timescale of up to 5 years
measure: Number of applications to, and outputs resulting from data repository
timeFrame: To be achieved within a timescale of up to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth Unviersity Hospital, NHS Greater Glasgow and Clyde Health Board
city: Leeds
country: United Kingdom
facility: St James's University Hospital, Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: The Walton Centre, The Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital, King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital, Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie Hospital, The Christie NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre, Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: Unviersity of Birmingham
name: Colin Watts
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.