Tessa Jowell BRAIN MATRIX - Platform Study
- Conditions
- Glioma
- Registration Number
- NCT04274283
- Lead Sponsor
- University of Birmingham
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1000
- 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.
- Primary spinal cord tumours
- Active treatment of other malignancy
- Contraindication to MRI
- Patients without standard of care imaging available
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time (from biopsy) to integrated histological-molecular diagnosis 28 days This is defined as the difference (days) between date of biopsy and date of whole genome diagnosis and epigenomic classification.
- Secondary Outcome Measures
Name Time Method Type of complications from treatments (standard of care) received. To be achieved within a timescale of up to 5 years 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.
Inter-rater agreement of Response Assessment in Neuro-Oncology (RANO) To be achieved within a timescale of up to 5 years Scans will be assessed and scored according to RANO criteria by the hub of Neuro-radiologists.
Extent of surgical resection To be achieved within a timescale of up to 5 years 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%.
Tumour and biological sample(s) quality control status To be achieved within a timescale of up to 5 years Tumour and biological sample collection will be measured against protocol guidelines. These data will be collected in the surgical and pathological forms.
Imaging quality control status To be achieved within a timescale of up to 5 years Imaging will be measured against established clinical guideline. The imaging form will measure compliance against these guidelines.
Intracranial progression-free survival time To be achieved within a timescale of up to 5 years 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.
Overall survival time To be achieved within a timescale of up to 5 years 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.
Concordance of diagnoses To be achieved within a timescale of up to 5 years 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.
Post-mortem sampling consent status and sample collection confirmation To be achieved within a timescale of up to 5 years Based on receipt of post-mortem consent form, and on post-mortem samples with confirmed central storage.
Time to completion of each node of tissue and imaging pathway To be achieved within a timescale of up to 5 years 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.
Type of interventions received To be achieved within a timescale of up to 5 years Details of the type of interventions received will be monitored throughout the follow-up period and recorded on the Case Report Form.
Samples and images centrally stored To be achieved within a timescale of up to 5 years Defined as confirmed central storage of images and material.
Targetable mutation(s) identified To be achieved within a timescale of up to 5 years Relevant targetable mutations identified by Whole Genome Sequencing and Epigenomic Classification.
Number of applications to, and outputs resulting from data repository To be achieved within a timescale of up to 5 years As per title.
Quality of Life (QoL) scores To be achieved within a timescale of up to 5 years Longitudinal measures of QoL will be generated from the QoL questionnaire according to the questionnaire-specific algorithm for scoring.
Trial Locations
- Locations (13)
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
St James's University Hospital, Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
The Walton Centre, The Walton Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
King's College Hospital, King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Charing Cross Hospital, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Queen's Medical Centre, Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
NHS Lothian
🇬🇧Edinburgh, United Kingdom
Queen Elizabeth Unviersity Hospital, NHS Greater Glasgow and Clyde Health Board
🇬🇧Glasgow, United Kingdom
Scroll for more (3 remaining)Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust🇬🇧Birmingham, United KingdomVictoria WykesContact