The DETERMINE study aims to use genetic testing to match children, teenagers and adults with rare cancers to existing targeted treatments. NCRI Groups provided valuable feedback during the development of the trial which is the first of its kind in the UK to establish a joint protocol for childhood, teenage and adult patient populations.
The increased availability of genetic testing in the UK has enabled researchers to identify specific mutations in tumours. Clinicians can then see if there are medicines licenced in other cancers that target the same mutation. The DETERMINE trial enables patients to access these treatments even if they haven’t been licenced in their cancer.
Rare tumours and tumours affecting teenagers and children account for approximately 20%, 1% and 1% respectively, of the overall cancer population in the UK. Researchers hope that this program will improve clinical outcomes for patients where there are often limited treatment options, thereby improving survival and enhancing physical and psychological wellbeing.
For a trial such as this involving adult, paediatric and teenage and young adult populations across all cancer types it was important for us to engage with a number of different experts. We approached as many NCRI Groups as we could before applying for funding to seek valuable guidance on the study.
Dr Matthew Krebs, Clinical Senior Lecturer in Experimental Cancer Medicine, The University of Manchester and Honorary Consultant in Medical Oncology, The Christie NHS Foundation Trust
The DETERMINE trial is the first of its kind in the UK to establish a joint protocol for childhood, teenage and adult patient populations across multiple disease types. When discussing the proposal, the NCRI Children’s Group suggested expanding the age range, which the researchers incorporated into the proposal. There is now no lower age limit set across the platform unless there is a specific known safety concern with a drug or the current formulation does not support dosing in younger patients.
The NCRI Groups were very supportive of our clinical trial proposal and translational plans. They suggested a number of helpful changes which we encorporated into the proposal. Having this input and support of the NCRI Groups undoubtedly strengthened our proposal.
Dr Matthew Krebs, Clinical Senior Lecturer in Experimental Cancer Medicine, The University of Manchester and Honorary Consultant in Medical Oncology, The Christie NHS Foundation Trust
The DETERMINE trial has a detailed translational element, which aims to identify which patients are more likely to respond to the treatments, according to the genetic context upon which the targeted mutation is sited. For example, the presence of other gene mutations or the nature of the tumour microenvironment could impact treatment response. The researchers contacted the NCRI Clinical and Molecular Pathology Group (CMPath) to get specific advice on the biomarker elements of the study. The researchers presented the study to CMPath members, including experts in clinical trial statistics, cancer genetics and molecular pathology.
CMPath members were supportive of the study but raised some concerns about tissue sampling standardisation across participating sites and where mandatory biopsy might not be possible or high risk. The researchers addressed these comments by developing a comprehensive research sample pathway and prioritisation list with standard operating procedures. For mandatory biopsies, exceptions have been incorporated in paediatric instances in which tissue may be available from within the last three months or where it would be unfeasible to acquire further tissue. In adult cases where the tumour is inaccessible, but there is the potential for high patient benefit or where tissue may be available from within the last three months, exceptions can be made for the mandatory biopsy following discussion with the chief investigator.
The researchers anticipate ongoing relationships with the NCRI Groups. As the study progresses, the groups will continue to provide feedback, disseminate trial messages and aid recruitment.