Paediatric pharmacology and early phase clinical trials in children and young adults
Our paediatric pharmacology group has been working over a number of years to learn more about how chemotherapeutic approaches can be optimised through an improved knowledge of drug disposition and metabolism in paediatric patient populations.
The benefits of individualised patient treatment in childhood cancer have been demonstrated in a number of clinical studies. By utilising a pharmacokinetic approach, individualised dosing regimens have been found to minimise side effects caused by differences in drug disposition in children in the UK with high-risk neuroblastoma receiving 13-cis-retinoic acid.
While we continue to carry out clinical trials to optimise the way that currently-used chemotherapeutics are dosed, an increasing amount of work is also now being carried out to progress novel agents for childhood cancer through preclinical and Phase I clinical trials. By incorporating pharmacokinetic and pharmacodynamic endpoints in addition to novel biological study approaches (target discovery, pre-clinical drug development and in vivo modelling), and having strong links with the drug development programmes, the development of new treatments is underway:
- Aurora kinase inhibitor AT9238 in both sold tumours and leukaemia patient populations
- PARP inhibitor AG014699 for paediatric solid tumours
Newcastle will continue to act as the Children’s Cancer and Leukaemia Group (CCLG) UK centre for conducting clinical pharmacology studies in paediatric oncology, with continued investment in the opening of new clinical trials alongside the publication of completed studies leading to further optimisation of the use of anti-cancer drugs in children.
Future initiatives
In close collaboration with the NICR drug development programme, the Great North Children’s Hospital and the Sir Bobby Robson Cancer Centre, will:
- Advance molecular classification of paediatric and haematological malignancies to identify novel prognostic biomarkers for therapy stratification
- Develop molecularly targeted therapies against cancer-specific alterations identified through basic research programmes
- Assess the relevance of drugs developed at the NICR for the therapy of paediatric cancers and haematological malignancies
The Great North Children’s Hospital will continue to act as the Children's Cancer and Leukaemia Group centre for:
- Running phase III trials for a wide range of malignancies for children and young people in the region
- Continued leadership on early phase clinical trials with new drugs as one of nine phase I/II centres for children and young people in the UK and an accredited centre of the Innovative Therapies for Children with Cancer (ITCC) consortium in Europe
Establishing and leading a series of early phase clinical trials in childhood cancer, exemplified by the Phase I trials of the PARP inhibitor AGO14699 and the Aurora kinase inhibitor AT9283 in both solid tumour and leukaemia
