Clinical research – key to improving outcomes in childhood cancer

Survival rates for children with cancer have improved significantly since the 1980s with estimated five-year survival rate rising from 28% to more than 80%. While newer modalities of treatment and better supportive care have contributed to this dramatic survival improvement, the important role played by clinical trials over the years cannot be underestimated. 

Dr Santosh Valvi, Paediatric Oncologist, PCH

Although about 400,000 children and adolescents are diagnosed with cancer globally each year, childhood cancers only account for 1% of all newly diagnosed cancers and are relatively uncommon. With limited patient numbers, collaboration among multinational consortia and cooperative groups to share research ideas and run clinical trials is essential.

As an oncologist, delivering difficult news to families regarding the clinical outcome for their child is never easy, but discussion of potential enrolment onto a clinical trial, changes that conversation by offering hope. We have a range of clinical trials open for our patients at Perth Children’s Hospital (PCH). 

Phase I clinical trials investigate a new drug, schedule, or combination of agents to determine safety and toxicity. Phase II trials investigate tumour-specific efficacy of an agent, in a dose and schedule determined from a phase I trial. Phase III trials compare a new drug or drug combination with the current standard treatment, usually in a randomised fashion. Early phase (phase I and II) clinical trials are not generally expected to result in a cure, though these provide children with incurable cancers and their families an opportunity of doing something rather than nothing. 

The PCH Oncology Unit has participated in clinical trials conducted by the Children’s Oncology Group (COG) and its predecessors since the early 1990s. For newly diagnosed children with cancer, enrolment into phase III and some phase II clinical trials represents a standard approach to paediatric cancer therapy.

All patients and their families are offered participation in clinical trials if available. They are enrolled after an informed consent process. We have established a strong record of success in recruiting patients in clinical trials with nearly all of our patients enrolled where an appropriate trial is available. In cases where a frontline phase III trial is temporarily closed or unavailable, patients are treated as per the standard arm of the latest clinical trial, which in many cases is the standard therapy available for that particular cancer. 

In addition to COG, we have established successful partnerships with local, national, and international groups. The PCH Oncology Unit has recently joined several other international clinical trials consortia, which will deliver a broad suite of new clinical trials. 

We have built strong collaborations with industry, allowing us to offer families access to novel treatments not otherwise available. We also collaborate closely with the Telethon Kids Institute Cancer Centre and have translated home-grown research into an international clinical trial called SJ-ELIOT, in partnership with the world-renowned St Jude Children’s Research Hospital in Memphis, USA, for patients with relapsed medulloblastoma.

In 2017, we expanded clinical trial capabilities following establishment of our specialist Early Phase Clinical Trials Unit. This ensures that all WA children with cancer have the opportunity to access the latest therapies (e.g. molecularly targeted therapy, immunotherapy, and precision medicine approaches). 

Precision medicine is an emerging paradigm in paediatric oncology using advanced molecular techniques to understand the genetic and biochemical profiles of cancers and guide the use of targeted therapies. It has predominantly been used when a patient relapses, however, we have also had the opportunity to use targeted agents in some newly diagnosed patients where standard therapy was considered to be less effective. This is a field with continual advances being made. 

Before opening this unit, travelling interstate was the only option for our patients wanting to participate in early phase trials. Since inception, a total of 33 new early phase clinical trials have been opened, with 67 patients enrolled, including recruitment of the first patients globally onto some of these trials. 

Achieving milestones such as this is not only the result of enormous work by our team but also reflective of the strong international reputation we have achieved and enables provision of world-class care for Western Australian children with cancer.

Key messages
  • Child cancer survival is improving
  • Clinical trials can offer hope as well as knowledge
  • This area is ever evolving.

Author competing interests – nil