Recipient organisationNIHR Great Ormond Street Hospital Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Jun 2027
In plain English
AI plain-English summary
Children with relapsed or refractory cancers in the UK will now receive tumour biopsies at the time of relapse to match them to targeted drug therapies in a single European trial. This matters because survival rates for children whose cancers do not respond to frontline treatments remain poor. Standard chemotherapy often fails these high-risk groups, and few new drugs have been tested specifically in paediatric tumours. The ESMART trial addresses this gap by repurposing drugs already used in adult oncology—such as ribociclib, olaparib, and nivolumab—that target the specific molecular pathways driving each child’s cancer. Instead of a one-size-fits-all approach, the trial requires extensive molecular profiling of a fresh biopsy to assign each patient to the treatment arm most likely to work. If successful, this approach could transform how relapsed childhood cancers are treated. It would shift paediatric oncology from broad chemotherapy to precision medicine, where treatment decisions are guided by the tumour’s genetic and molecular features. The trial’s adaptive design also allows new drug arms to be added as they become available, accelerating the testing of promising therapies. Beyond individual patient benefit, the study will generate data on which molecular anomalies predict response, informing future trial design and drug development for children with cancer.
View original technical description
Despite the good overall survival in children and adolescents with cancer, outcomes remain poor for high risk groups and those that do not respond to frontline therapies. Better treatment options which work in novel ways are required. A number of drugs that target the specific underlying pathways which allow individual cancers to grow have been developed in adult oncology and have potential to be effective in paediatric tumours. ESMART is a European trial which will offer children and adolescents with different types of relapsed or refractory cancer who have exhausted standard treatment access to several new drugs/drug combinations as part of a single umbrella study with multiple arms. A unique feature of entry to the trial is the requirement for results from extensive molecular analysis from a biopsy at the time of relpase (biopsy and analysis not part of ESMART) so that the treatment arm offered is the ‘best fit’ in targeting the biology of each patient’s cancer. This will be the first study in the UK to routinely offer this advanced tumour profiling in children and adolescents. The hope is that this approach will increase the chances of the drug working and expand our knowledge of what molecular and genetic features predict therapeutic response. The trial aims to first identify the safety and correct dose of these treatments in children using knowledge from adult trials and where there seems to be evidence of anti-tumour activity to enrol more patients to assess if these drugs are effective. An efficient study design has been adopted to accelerate these drug development objectives and with the option to add treatment arms as new drugs become available. The following drugs are currently being tested in this trial: Ribocliclib, Topotecan, Temozolomide, AZD1775, Carboplatin, Olaparib, Irinotecan, Nivolumab, Enasidenib, Lirilumab.
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