Clinical trial results give new hope for children with rare brain tumours

Their work has shown a combination of drugs, which are already used to treat some other types of cancer in adults, can be effective in treating children with rare cancerous brain tumours, called BRAF mutated gliomas.

For low-grade tumours, the new treatment could be offered as an alternative to chemotherapy. For high-grade, more aggressive tumours, it means there is another treatment option if a patient relapses.

Researchers from around the world took part in the study, which was led at Great Ormond Street Hospital for Children (GOSH) by Professor Darren Hargrave and is the first to test if the drugs Dabrafenib and Trametinib can both be used to treat BRAF mutated brain gliomas in children.

The BRAF mutation is present in around 15-20% of paediatric low-grade tumours and around 5-10% of high-grade tumours in children.

For children with paediatric low-grade tumours, the normal course of treatment is a full surgical removal. However, for children where this is not possible additional treatments like chemotherapy are required. The low-grade trial showed the Dabrafenib and Trametinib treatment was four times more effective that chemotherapy and had fewer side effects.

For high-grade tumours, the treatment is usually surgery and then chemotherapy and radiotherapy - but unfortunately the overall response rates to this treatment is less than 20%. When the children were treated with Dabrafenib and Trametinib, the response rate increase to 56%.

Aaliyah joined the trial after being referred for an MRI scan following a routine eye appointment. The MRI scan showed a tumour and Aaliyah was referred to Addenbrooke’s Hospital and then to GOSH.

Operating wasn’t possible and so after a year of ‘watch and wait’, the family were offered to join the TADPOLE0G trial at GOSH.

Mum Amie spent a lot of time researching the options, including speaking to other families. In 2020 they decided to join the randomized trial and Aaliyah was given Dabafenib and Trametinib, instead of chemotherapy.

She said: “We got a letter about a six-month eye check-up. We didn’t think we needed it as Aaliyah didn’t need glasses, but I thought I should ring just in case. She didn’t have any other symptoms at all, so we were so shocked – how could there by a tumour without causing any problems.

“Three months after we started the trial, we had an MRI. That was the first time I felt able to look at the scans. When I saw the before and after, that was probably the day a massive weight was lifted off my shoulders. I didn’t expect it to shrink that much, I knew we’d made the right decision.

“Aaliyah is completely fine and pretty much lives life as normal. Sometimes it even feels like we forget about it, but this wasn’t the case before, I would have been panicking all the time. She even enjoys the hospital trips as we try to make them fun.”

Aaliyah said: “I do feel proud in a way, that I’m part of something that can help other people and I am thankful to the team who have supported me.”

Another family joined the trial after noticing a subtle tremor in their daughter’s left hand while eating and playing. Scans show the two-year-old patient had a low-grade glioma.

Her dad said: “One of the best things about the nature of this trial is that all the medication can be provided at home. Not only the treatment has proven effective from the very beginning, but at the same time it allowed our daughter to live a normal life

“If we’d had chosen chemotherapy, our and our daughter’s life would have been radically different. She would have spent much more time in the hospital, away from her baby sister, her nursery and her friends, and we, as parents, would have had to adapt our life and work schedule around weekly hospital appointments.

“Being on this trial and having helped demonstrate the effectiveness of these drugs made us feel like we have done something important not just for our daughter but also for those children that unfortunately will receive her same terrible diagnosis in the future”

“Right now, my daughter still doesn’t understand how scary the word “tumour” is, but one day she will. And I think she will be thankful for the opportunity that she has been given with this trial and happy for having been part of something that will help other people.”

Professor Darren Hargrave, GOSH Children's Charity Clinical Professor in Paediatric Neuro-Oncology at the UCL Great Ormond Street Institute of Child Health and Honorary Consultant Paediatric Oncologist at GOSH, said: “It has been incredible to watch research move our ability to treat specific cancers forward at such a rapid pace. I was involved in the original study that identified BRAF gene mutations as drivers of cancer and so it has been fantastic to now be able to see treatments that target the mutation in clinical trials for paediatric gliomas. These studies demonstrate the power of collaborative, global research to find new treatments for rare cancers. We’d like to thank all the patients and families who make research like this possible.”

Evidence from these trials is now being used as part of a National Institute for Health and Care Execellence review to appraise the clinical and cost effectiveness of the treatments. The Food and Drug Administration in the USA has already approved the treatment for children with low-grade glioma.

Replacing outdated buildings on Great Ormond Street, our new Children’s Cancer Centre will mean that children with rare and complex cancers will receive care in the best possible environment, making it easier for them to be able to play, continue with school and participate in normal activities. The CCC will also enhance our ability to research and innovate to develop new and kinder treatments for cancer.

With significant outside space, a new hospital school, child centre inpatient wards and day care spaces, imaging, theatres and critical care services linked to the existing hospital, children and young people coming to GOSH will have access to the very latest technologies and receive care and treatment in environments that reflect their needs.

For more information visit Children’s Cancer Centre.

GOSH Charity is fundraising for the Children’s Cancer Centre, find out more about how you can be part of Build it Beat it.