Each year, 150 children in the Netherlands are diagnosed with a tumor of the central nervous system - in the brain or spinal cord. Ten of these children are diagnosed with the type called diffuse midline glioma (DMG). Currently, there is no treatment to cure this group of children. Consequently, numerous research groups are active at the Máxima Center and worldwide to find a new treatment for them. An important step to get here are clinical trials with promising discoveries from the laboratory. Because the Máxima Center is part of the International Pacific Neuro-Oncology Consortium (PNOC), children and, in the case of this study, young adults up to age 39, with DMG can participate in such a study at the Máxima Center.
Important step forward
Jasper van der Lugt, pediatric oncologist and coordinator of the trial: ‘In this study we are investigating the efficacy of a new combination therapy, consisting of two targeted drugs. I am very happy that with the start of this study another important step forward has been taken within this disease area. We see a lot of interest, including from abroad, in this study from the group of children diagnosed with DMG.'
This study is an early-stage clinical trial and the Máxima Center is one of the 22 participating centers worldwide. Currently, one child and one young adult are under treatment at the Máxima Center. If these trials show positive results, they will be followed up with larger-scale studies. 'Together with PNOC, we have the goal of opening several early-stage studies with new drugs, for children and young adults with brain tumors. '
New combination therapy
The goal of the PNOC022 trial is to investigate the efficacy of a new combination of existing drugs: ONC201 and paxalisib. Within a previous clinical trial, some children with DMG with the so-called H3K27M gene abnormality continued to live longer after treatment with ONC201. Van der Lugt: ‘Even though we are talking about a prolongation in months here, it is an improvement that we have not seen in previous studies. By combining ONC201 with other drugs, we hope to see a further improvement in survival, even if it may only be a few months.'
In addition, this study is looking for biomarkers. These biological marks may help determine which children could benefit from the new treatment. 'The Máxima Center plays a central role in this. For example, our scientists are investigating the microbiome, the bacteria and fungi that live in your intestines, in all children participating in the study and whether this affects the effectiveness of the treatment.’
PNOC study platform
PNOC aims to accelerate the search for new treatments for brain tumors, including DMG, through collaboration and early phase clinical trials. Van der Lugt: ‘As the largest pediatric cancer center in Europe, the Máxima Center is an important partner within PNOC. Because we treat all children with a brain tumor in the Netherlands, our research group is large compared to other pediatric oncology hospitals. In addition, there is a lot of specialist knowledge and expertise in-house which allows us to coordinate the trial in Europe.'
The clinical trial is a platform study. This allows the researchers to conduct multiple ONC201-related trials under one protocol. 'This design gives us the opportunity to significantly accelerate research and get closer to a possible new treatment for children with DMG. The first study has now started and we hope to open new studies soon.'
Veer(le)kracht
Thanks to the Dutch foundation Veer(le)kracht, the Máxima Center's participation in this trial was made possible. Veerle (12) was diagnosed with DMG in 2022. 'Together with family and friends, the Veer(le)kracht foundation was established. The first goal was to raise money to start this trial. The foundation is very proud that this succeeded. For Veerle, the trial with the drug ONC201 turned out not to be the best option. In her specific case, the drug avapritinib could work well. She has been receiving this drug for a few weeks now. It highlights once again the great importance of much, different multidisciplinary and bold research.'
On March 8, 2023, Veerle died at the age of 13.
More information about this clinical trial including criteria for participation can be found on the PNOC website. If you have questions about participating in this trial, please contact your child's treating physician.
This trial was made possible thanks to funding from the Chad Tough Defeat DIPG Foundation, Storm the Heavens, and Mithil Prasad Foundation. Thanks to the Dutch foundation Veerlekracht (www.veerlekracht.nl), the Máxima Center's participation in this trial was made possible.