PNOC022; DMG-Act (diffuse midline gliomas)
Active, not recruiting
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
Goal
Goal
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.
Background
Background
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
Last reviewed
March 23, 2026
Study details
- Study details
Official title
PNOC022: A Combination Therapy Trial using an Adaptive Platform Design for Children and Young Adults with Diffuse Midline Gliomas (DMGs) including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of ProgressionCancer type
Diffuse midline gliomasPhase
2Maximum number of patients
120, of whom 5-10 are expected to participate in the NetherlandsStart date
November 22, 2022Status
On holdLocal principal investigator
Dr. J. van der LugtSponsor
University of California, San FranciscoApproval
The study of this new treatment has been reviewed by an accredited medical research ethics committee. This committee has decided that it is justified to ask patients to participate in this study. More information can be found at: CCMO.
Trial registry number
Clinicaltrial.gov: NCT05009992
EU Clinical Trials Register: 2022-000636-40
The above information is intended as a brief summary only and may not reflect the most up-to-date information. For full details and the current status of a protocol, physicians can contact the Princess Máxima Center directly.