Australian-first trial gives new hope for brain cancer

An Australian-first clinical trial giving hope to children diagnosed with a terrible brain tumour, Diffuse Intrinsic Pontine Glioma (DIPG), has opened at The Children’s Hospital at Westmead (CHW).

DIPG is a devastating childhood cancer that sadly lacks effective treatment. The average survival is between nine and 18 months from diagnosis.

The Children’s Hospital at Westmead is currently one of nine sites worldwide to open the trial, known as PNOC-022, which is testing the effectiveness of promising new drug combinations, including the oral drug ONC201.

Associate Professor Geoffrey McCowage, National Principal Investigator for the trial and Senior Paediatric Oncologist at CHW, says the preliminary results of children treated with ONC201 overseas has already generated a lot of interest and excitement about the potential of the trial.

“The early results in children treated with ONC201 for DIPG have shown some tumour responses and periods of disease control that we haven’t seen with other drugs,” A/Prof McCowage said.

“We are hopeful that we will end up proving that ONC201 is a step forward and hopefully the other drugs in the trial will be as well.”

For decades researchers have completed multiple clinical trials to find a drug to help change the outcomes for children diagnosed with DIPG, but with limited success.

By using an adaptive approach, researchers hope this trial will garner better results through the ability to test the effectiveness of ONC201, in combination with Paxalisib, and other new drugs as they become available.

“This research is a sophisticated international effort in evaluating new drugs in the treatment of this terrible disease,” A/Prof McCowage said.

“It’s only through adaptive clinical trials like this that we can work out if new drugs are effective without needing to keep opening multiple separate trials, and determine if these drugs should be routinely added into treatment for future children.”

While focussed on DIPG, the trial will also evaluate the success of these combination therapies in treating Diffuse Midline Gliomas (DMG), cancers located in other parts of the brain. These cancers have recently been identified as having the same genetic make-up in the tumour cells as DIPG.

Dr Dinisha Govender, local leader at CHW for the trial and Paediatric Neuro-oncologist, says because of this identification they believe the same treatments may work for both tumours.

“Scientists found children with DIPG and DMG were born with normal DNA, but later on a brain cell made a mistake. That mistake was a spontaneous mutation in a particular gene, called H3K27M which was found to be present in DIPG tumours and DMG tumours occurring elsewhere in the brain,” Dr Govender said.

“Now we know about these identical abnormalities in the tumours, we can expect the same treatments to apply to both groups of patients, offering new hope to families who were previously told there was nothing that could be done.”

The trial will run over the course of several years, with scheduled periods of pause to analyse the data.

The trial is expected to be rolled out at Sydney Children’s Hospital, Randwick, and other children’s cancer centres across Australia over the coming months.

“As a Network, we are excited to collaborate with colleagues internationally on this trial and continue advancing cancer research so one day families don’t have to hear the words “there’s nothing more we can do”,” A/Prof McCowage said.

The PNOC-022 trial has been developed by the Pacific paediatric Neuro-Oncology Consortium (PNOC) and is being sponsored in Australia and New Zealand by the Australian and New Zealand Children’s Haematology/Oncology Group.

Take a look at some of our other research projects

Across the Children's Cancer Research Unit at CHW, there are approximately 80 research projects currently being conducted relating to childhood cancer:

  • Prof Geraldine O’Neill and Sam Bax, from the Functionally Applied Biology (FAB) team are working with mini brains, hoping to find ways to protect brain health in children being treated for brain cancer.

  • Drs Bhavna Padhye and Yuyan Chen, from the Molecular Genomics (MolG) team are running the PREDICT study together with teams at Sydney Children's Hospital, Randwick and the Children's Cancer Institute to examine the whole genome of oncology patients and help clinicians to understand the role of inherited genes play in the development of childhood cancer.

  • Dr Smadar Kahana-Edwin & A/Prof Jonty Karpelowsky from the Advanced Molecular Diagnostics (AMD) team are working on a project to detect tumour DNA in patients via a simple blood test. The research is hoped to minimise invasive testing for children in the future.

  • Dr Kavitha Gowrishankar & A/Prof Geoff McCowage from The Advanced Cellular Therapeutics (ACT) group are working on using cutting-edge genetic and genome engineering technologies to modify patients’ own immune cells to identify, target and destroy cancer cells, providing novel immunotherapies for children to treat their cancers and is planning to start a clinical trial in the near future.

  • A/Prof Daniel Catchpoole and the Biospecimen Research Services (BRS) Team are distributing tissue microarray slides to researchers around the world so spatial transcriptomics and proteomics can be explored.

September is Childhood Cancer Awareness Month and is an opportunity to shine a spotlight on childhood cancer, a disease that affects so many children and families across both The Children’s Hospital at Westmead and Sydney Children’s Hospital, Randwick.