The Brain Tumour Charity has announced a £1.5 million commitment to CONNECT TarGeT, an ambitious adaptive umbrella clinical trial designed to accelerate new treatments for childhood brain cancers. The phase II trial represents a precision medicine approach for patients aged 12 months to 25 years newly diagnosed with paediatric high-grade gliomas, including Diffuse Midline Glioma (DMG), some ependymomas and embryonal brain tumours.
The transatlantic clinical trial will test different drug combinations tailored to specific genetic characteristics of childhood brain cancers. This molecularly guided approach uses detailed tumour information, including genetic mutations and biomarkers, to match patients with treatments most likely to be effective for their specific cancer profile.
Precision Medicine Framework
Once enrolled, participants undergo genetic screening to identify their tumour's molecular profile. Patients are then assigned to relevant treatment "arms" testing specific drug combinations alongside standard surgery and radiotherapy. The adaptive design allows patients to be moved to more promising treatments if necessary.
The Brain Tumour Charity is funding the screening protocol and Arm A, the first treatment arm to open in the UK. This arm will test everolimus and ribociclib on patients whose tumours have alterations in the PI3K/mTOR pathways. A second component of Arm A will test temozolomide and ribociclib against the same pathway.
Additional treatment arms will subsequently open, each targeting different genetic mutations including the MAPK pathway, ACVR1 and IDH1 mutations with tailored therapies. All drugs involved have undergone extensive laboratory testing and many have been evaluated in pilot clinical trials such as BIOMEDE.
Addressing Critical Unmet Need
The trial addresses a devastating clinical reality for families affected by paediatric high-grade gliomas. Life expectancy for childhood brain cancers like DMG, formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), is 9-12 months with no known cure. Patients diagnosed with paediatric high-grade gliomas have less than 10% chance of surviving five years after diagnosis, despite surgery where possible and available treatments including intensive radiotherapy and chemotherapy.
"Paediatric high-grade gliomas are among the hardest of all brain tumours to treat, with devastatingly poor survival rates. New, effective treatments are desperately needed," said Dr Michele Afif, Chief Executive at The Brain Tumour Charity. "This clinical trial is a beacon of hope demonstrating that much needed change is possible."
In the UK, brain tumours are the leading cause of death by cancer in people under 40, highlighting the urgent need for more effective treatments.
International Collaboration
The study operates through the CONNECT Consortium (COllaborative Network for Neuro-oncology Clinical Trials), a global partnership of childhood cancer centres and paediatric neuro-oncology experts across North America, Europe and Australia. In the UK, the trial is coordinated by the Clinical Trials Unit at the University of Birmingham and led by Professor Darren Hargrave, a consultant paediatric neuro-oncologist at Great Ormond Street Hospital.
"This trial is an ideal example of the future of adaptive trials that can more powerfully and quickly find potential treatments for children with cancers of the brain," said Professor Amos Burke, Director of the Cancer Research UK Clinical Trials Unit at the University of Birmingham.
The trial will operate across NHS children's cancer centres in the UK, as well as institutions in the USA, Germany, the Netherlands, Australia and New Zealand. It represents the only clinical trial for this type of brain tumour currently available in the UK.
Community Support and Funding
The £1.5 million commitment from The Brain Tumour Charity includes £791,000 contributed by key supporter groups including The Albie Sugden Foundation, Eva's Angels, Shay's Smiles and Joss Searchlight. Notable contributors include The Samantha Dickson Fund and The Silas Pullen Fund, which became the first supporter group to raise more than £1 million for the charity.
These funds reflect the personal experiences of families affected by paediatric brain tumours, including Eva's Angels, established by parents of Eva Giles who died in 2017 aged five after DMG diagnosis.
Trial Design and Timeline
CONNECT TarGeT is designed as a five-year phase II umbrella trial that will recruit patients over four years with multiple treatment arms opening sequentially. Patients must have tumour tissue available for testing during the screening phase, with samples used for DNA sequencing and molecular analysis to understand tumour growth mechanisms and genetic drivers.
The trial will monitor tumour size, treatment side effects, and quality of life impacts through regular check-ups, scans and surveys. While contracts are being finalized and regulatory approval sought, the UK launch is anticipated for Spring 2026.
Eligible participants include children and young adults aged 12 months to 25 years newly diagnosed with World Health Organisation grade 3-4 paediatric high-grade gliomas, including DMG. The trial is expected to open at all NHS children's cancer centres across the UK.
