Interview: Guy Makin, Paediatric Network

The ECMC Paediatric Network brings together clinicians and translational scientists to run early phase clinical trials in children and young people with cancer across 12 centres in the UK..

Dr Guy Makin, ECMC Paediatric Network Lead, talks about the challenges and opportunities for early phase paediatric research.

Why did you get involved with the ECMC Paediatric Network?

Children’s cancer has always been managed in a collaborative and networked fashion. There aren’t many children with cancer in the UK, so in order to answer questions about how to make their treatment better, you need to involve them all, regardless of where they are treated.

One of the fundamental principles of the network has always been about ensuring that children have the same opportunity to participate in trials regardless of where they live in the UK. Bringing the existing early phase paediatric centres into a network was a logical extension of the way we already thought about working in late phase trials. For me, it was an exciting opportunity to get a wide range of people to think about what we actually needed in the UK in terms of translational research in childhood cancer.

How does the Network benefit children and young people with cancer?

The network ensures that experimental cancer medicine trials are open in as many centres as possible, to give all children and their families the opportunity to take part in an experimental cancer medicine trial, if they wish to do so. Importantly, the network aims to ensure that trials are open in geographically disparate locations to try and minimise the distances that children and their families have to travel to access experimental treatment.

The creation of four regional panels, at which children who might be eligible for trials are discussed, ensures that experimental medicines are considered for virtually all suitable children in the UK. The ECMC-funded research nurses across the network are experts at making sure that appropriate biological samples are collected from patients for tumour banking, for pharmacokinetics studies and the Stratified Medicine Paediatrics programme, to ensure that every family is able to contribute to research as much as possible. Without this, our trials would take longer to complete, and would tell us far less, and it would take longer before new approaches made it into front line treatment.

What are the current major challenges in early phase paediatric research?

The major challenges are the same as they have always been for children: getting access to new drugs and co-ordinating international trials to recruit rare patients to answer questions as quickly as possible.

Childhood cancer is fundamentally different to adult cancer, and often the biological abnormalities in children’s tumours are very different to those in adult cancers. Thus, mechanism-based therapeutics designed to specifically target molecular abnormalities in adult cancer are often not useful for children. Conversely, the market for developing mechanism-based agents to target molecular abnormalities found only in children’s cancer is small, and the financial returns on investments not likely to be great.

With the increasing use of genomic profiling of tumours at relapse (as in SM-PAEDS) we are learning more and more about the molecular abnormalities seen in childhood cancer at relapse, and this allows us to develop novel trials to match individual patients with available targeted therapies. These trials need to be pan-European in order to recruit enough patients to answer questions in a sensible time frame, and be designed in such a way as to adapt to include different targeted agents as they become available, without having to start the entire study from scratch for each new drug.

Can you tell us about some of the Network initiatives that excite you most for the future?

With SM-PAEDS open and recruiting well, we are now able to identify children whose relapsed tumours contain actionable molecular abnormalities. The multiple arms in the European eSMART trial allow us to match these children with available mechanism-based agents. The regional networks mean that we can maximise the numbers of children having tissue taken at relapse for molecular profiling in SM-PAEDS, and we can direct children to appropriate studies. Thus, the building blocks are in place to develop a comprehensive understanding of what molecular targets are found in childhood cancer at relapse, and the framework is in place to allow rapid testing of the efficacy of novel mechanism-based therapeutics.

This is an exciting time for us as paediatric oncologists, with the tantalising possibility of understanding how to use new targeted agents to treat relapsed disease better, and translating that into improved treatment for frontline disease.