Interview: Guy Makin, Paediatric Network
The ECMC Paediatric Network brings together researchers working in early phase trials in children’s cancers at nine centres across the ECMC Network.
Dr Guy Makin, who leads the group, talks about the challenges and opportunities for paediatric research.
Children’s cancer treatment in the UK has always functioned as a national network. It’s the only way of doing useful clinical trials in relatively uncommon tumour types, so collaborative working is all that I have known during the 18 years that I have been in paediatric oncology.
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. The invitation to submit an application for a network for childhood cancer was pushing at an open door.
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.
National and international collaboration has always been a big part of childhood cancer and leukaemia treatment in the UK, but this was very much focussed around late phase clinical trials.
Through the NCRI Children’s Cancer and Leukaemia New Agents subgroup, we had a governance structure where all the UK phase 1 centres were represented, but we had no formal network. This meant that we lacked a coherent voice and, as individual centres, we were all small fish in the big sea of adult cancer.
The creation of the ECMC Network has led to detailed discussion and agreement about what we want to achieve. By bringing everyone together this has given us far more of a presence, both within cancer treatment in the UK and to industry.
Over the last 40 years there have been major improvements in survival rates for a wide range of childhood malignancies. However, there are still several tumour types where we either have no effective treatment, such as diffuse intrinsic pontine glioma, or where we have not been able to achieve significant improvements.
We need new approaches to these diseases as our traditional approach, optimising combinations of cytotoxic agents, has not worked.
We need more understanding of potential novel drug targets in these difficult-to-treat cancer types, and we need to better understand how to combine new mechanism-based therapeutics with conventional cytotoxic agents.
It is very easy to dismiss childhood cancer as rare and easily treated, and thus to not think about new drug development. So, most importantly, we need to work together to keep new treatments for childhood cancer high on the national agenda.
When the current European Paediatric Medicine Regulation was introduced in 2007, there was widespread belief that this would lead to a major increase in the availability of novel drugs to investigate in childhood cancer.
However, the extensive use of the class waiver has allowed pharmaceutical companies to avoid having to investigate the potential use of new anti-cancer drugs against childhood tumours if the drug was originally developed to treat a cancer type that does not occur in children.
Fortunately the EMA seems determined to scrap the class waiver, which will hopefully lead to a significant increase in the numbers of novel drugs becoming available for investigation in childhood cancer.
The network has been very effective at bringing centres together. This has allowed us to achieve consensus across the UK about how new early phase studies will be distributed, and it allows us to present an organised national network to industry for potential new studies.
Working with NCRN and MCRN allows rapid review of industry studies and evaluation of their place within the UK portfolio. This has resulted in industry favouring UK sites for international studies, so we had 28 early phase studies open or in set-up in the UK in January 2013, compared with 17 a year earlier.
The more we are able to demonstrate that we can deliver these studies, the more we can develop in the future.
The MAGIC collaboration led by Liverpool, looking at the molecular genetics of adverse drug reactions in children, is very exciting. We know that there is considerable variation between patients in the toxicity of anti-cancer agents, but we only understand the reasons for this in a minority of cases.
This project is about identifying genetic variation that leads to excessive drug toxicity, with the hope that this will allow individualisation of drug treatment to minimise toxicity.
Several parts of the paediatric network are already involved in recruiting patients and samples to look at the ototoxicity of cisplatin. This is a great example of how we can use the paediatric network to answer important questions that will improve treatment for childhood cancer.
Another important and exciting area is the development of functional imaging capacity across the paediatric network, led by Professor Andrew Peet from Birmingham.
Our aim is to be able to perform modalities such as dynamic contrast enhanced MRI in all the network ECMCs, and to include this type of imaging in as many early phase trials as possible as a means of disseminating expertise across the network.
Traditionally a lot of paediatric oncologists will have treated TYAs, so a lot of the same people are involved. TYA cancer has a similar philosophy of treatment to paediatric cancer, and there is considerable overlap of tumour types between the two age groups, so a number of studies, such as UKALL2011, are open to both age groups.
There are also similar problems around the rarity of disease when compared to adult cancer, so there is a similar need to be robust about the differences between TYAs and older adults, and similar benefits from collaboration across a network.
There are some specific TYA issues about under-representation in trials and recruitment, which are not such an issue in children but, by making sure trials are open over age ranges that include TYAs, this will hopefully improve.