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PNOC022; DMG-Act (diffuse midline gliomas)

Clinical study of a new treatment of diffuse midline gliomas.
Who can enter
  • Children with diffuse midline gliomas, including diffuse intrinsic pontine gliomas (DIPG); newly diagnosed, after radiotherapy or with progression
  • Age: 2 years and older


The aim of this study is to see whether a new treatment combination for diffuse midline glioma works. The new treatment consists of a combination of two drugs: ONC201 and a second drug. Paxalisib is currently being investigated as a second drug in combination with ONC201. Additional study arms may be added later in which we investigate other drugs in combination with ONC201.


A diffuse midline glioma is a malignant tumor in the brain or spinal cord that is difficult to treat. In this study we want to investigate whether a new treatment combination of the drug ONC201 with a second drug works in the treatment of diffuse midline glioma.

ONC201 is a new drug that induces a stress response in tumor cells. This stress response leads to all kinds of anti-cancer effects, causing the tumor cells to eventually die. ONC201 has previously been used in medical research in adults and children with various cancers, including brain tumors. These studies show that treatment with ONC201 can extend life expectancy.

We are currently investigating the treatment combination of ONC201 and paxalisib. In many tumors there are abnormalities (mutations) in certain processes within the tumor cells. One of these processes is called the PI3K/mTOR pathway. An abnormality in this pathway ensures that cancer cells can grow better. This is also the case with most diffuse midline gliomas. Paxalisib inhibits this pathway. By inhibiting this pathway, tumor growth is also inhibited. In addition, paxalisib potentiates the action of ONC201.

The primary aim of the study is to see if these drugs can extend the lives of patients with diffuse midline glioma. The drugs can be used as long as the disease does not get worse and there are not too many side effects.

We also want to see how much of the ingested ONC201 or the second drug (paxalasib) actually ends up in the tumor. For this, we ask children to take ONC201 or the second drug before surgery. During the planned operation, we take tumor tissue and check how much of the medicine is in the tumor tissue. We only do this part for children who would also receive an operation/biopsy in normal care.

We also want to examine the effect of ONC201 or the second drug in combination with radiotherapy treatment. We only do this part for children who would also receive radiotherapy in normal care.

This study is temporarily closed for inclusion.

Last reviewed

February 1, 2024