Study of ONC206 for children and young adults with newly diagnosed or recurrent diffuse midline glioma and other recurrent brain tumors

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What is this study about?

This study examines the use of ONC206 in children and young adults with brain tumors, specifically Diffuse Midline Glioma and other returning cancerous brain tumors. Diffuse Midline Glioma is a type of aggressive brain tumor that grows in the middle structures of the brain, often in areas like the brainstem or thalamus, and has a specific genetic change called H3K27 alteration. The study also includes other types of returning cancerous tumors of the brain and spinal cord. ONC206 is a medication given by mouth that works by affecting certain parts of cells called mitochondria and by blocking specific receptors in the body. The medication comes as a powder that is mixed into a liquid solution for drinking.

The purpose of this study is to find the right dose of ONC206 that can be given safely to patients and to check whether the medication reaches the tumor tissue in the brain. The study is divided into different groups based on the type of tumor and previous treatments. Some patients will receive ONC206 alone, while others will receive it together with radiation therapy, which is a treatment that uses high-energy rays to target cancer cells. Some participants will receive ONC206 with a second course of radiation therapy if their tumor has grown back. There is also a part of the study that will measure how much of the medication gets into the tumor tissue by comparing it to the levels found in the blood before surgery.

During the study, patients will take ONC206 regularly and will have blood tests to check how the body processes the medication and to monitor for any side effects. Patients will also have imaging scans to see how the tumor responds to treatment. Some participants will need to provide tumor tissue samples that were collected during their standard medical care so researchers can study how the medication works in the tumor. The study will continue to monitor patients over time to gather information about safety and how well the treatment works.

1 Treatment with ONC206

The treatment involves taking ONC206, which is provided as a powder for oral solution. This means the powder will be mixed with liquid before being taken by mouth.

The dose of ONC206 will be determined based on the specific treatment group and the phase of the study. The study aims to find the maximum tolerated dose, which is the highest amount that can be given safely without causing unacceptable side effects.

The treatment schedule and duration will depend on which treatment group applies. For some groups, ONC206 will be given alone, while for others it will be combined with radiation therapy.

2 Treatment monitoring during the first cycle

For treatment groups receiving ONC206 without radiation therapy, the first treatment cycle lasts 4 weeks. During this time, careful monitoring will occur to assess how the body responds to the medication and to identify any side effects.

For treatment groups receiving ONC206 combined with radiation therapy, the monitoring period will last for the duration of the radiation treatment.

Throughout this period, safety and tolerability of the medication will be assessed.

3 Blood tests for medication levels

Blood samples will be collected to measure the levels of ONC206 in the bloodstream. This is called pharmacokinetic assessment, which helps understand how the body processes the medication.

These blood tests help determine how much medication reaches the blood and how long it stays in the body.

4 Radiation therapy (if applicable)

For newly diagnosed patients in the appropriate treatment group, focal radiation therapy will be given in combination with ONC206. Focal radiation means the radiation is directed specifically at the tumor area.

For patients with disease progression in the relevant treatment group, re-irradiation may be given in combination with ONC206. Re-irradiation means receiving radiation therapy again to an area that was previously treated.

The radiation therapy will be administered according to standard protocols for the specific condition.

5 Tumor tissue collection (for specific participants)

Some participants will have tumor tissue collected as part of their standard medical care. This tissue will be used to measure the concentration of ONC206 in the tumor.

This measurement helps determine if the medication crosses the blood-brain barrier, which is a protective layer that normally prevents many substances from entering the brain tissue.

The tumor tissue levels will be compared to the medication levels found in the blood samples collected before any surgical procedure.

6 Ongoing treatment and assessments

After the initial monitoring period, treatment with ONC206 will continue as determined by the study protocol and the treating physician.

Regular assessments will be performed to monitor the response to treatment and to check for any side effects.

If corticosteroids (medications that reduce inflammation and swelling) are being taken, the dose must remain stable or be decreased for at least 3 days before certain study milestones.

7 Continuation of study participation

The study is expected to continue until May 2029, though individual participation duration may vary.

Throughout the study, various tests and evaluations will be performed to assess how well the treatment is working and to monitor overall health.

The specific schedule of visits and assessments will be provided by the study team.

Who Can Join the Study?

General Requirements for All Participants:

You must be at least 2 years old
You must be willing to provide tissue samples from your tumor. This means at least 10 to 20 slides or 1 tissue block that contains at least 40 percent tumor material
You or your parent or legal guardian must be able to understand and sign a consent form
If you are taking steroids, which are medicines that reduce swelling in the brain, your dose must be stable or decreasing for at least 3 days before joining the study
Your body must have adequate bone marrow function, which means your body must be able to make enough blood cells. Your neutrophil count, a type of white blood cell that fights infection, must be at least 1.0, and your platelet count, cells that help blood clot, must be at least 100 without needing transfusions for 7 days
Your kidneys must be working well enough, with creatinine levels, a waste product measured in blood, less than 1.5 times the normal upper limit for your age and gender
Your liver must be working well enough, with bilirubin, a substance produced when red blood cells break down, no more than 1.5 times the normal upper limit, and liver enzymes called ALT and AST no more than 3 times the normal upper limit
If you have a seizure disorder, which means you have episodes of abnormal electrical activity in the brain causing convulsions, it must be well controlled with treatment
You must have a Karnofsky score of at least 50 if you are older than 16 years, or a Lansky score of at least 50 if you are 16 years or younger. These scores measure how well you can perform daily activities. If you cannot walk due to paralysis, being unable to move parts of your body, but can use a wheelchair, you are still considered able to move around
If you are able to have children, you must agree to use birth control during the study. If you become pregnant or think you might be pregnant during the study, you must tell your doctor immediately

For Arm A (patients with DMG who already received radiation therapy):

You must have a type of brain tumor called Diffuse Midline Glioma or DMG with a specific change called H3K27 altered
Tissue testing must confirm you have DMG with the H3K27 alteration
You must have completed at least one previous treatment that included focal radiation therapy, which is targeted radiation treatment to a specific area of the brain
You must be between 4 and 14 weeks after finishing radiation therapy when you join the study
You must start treatment within 1 week of joining the study
You must not have started any other treatments after finishing radiation
Your tumor must not show signs of growing or getting worse
You must have recovered from all sudden or severe side effects from previous treatments
Enough time must have passed since your last treatment: 5 half-lives for experimental drugs, 4 weeks for most chemotherapy drugs, 23 days for a drug called temozolomide, 6 weeks for drugs called nitrosoureas, 4 weeks for antibody treatments, and at least 7 days for biologic or small molecule drugs

For Arm B (newly diagnosed patients with DMG):

You must be newly diagnosed with Diffuse Midline Glioma or DMG with the H3K27 alteration
Tissue testing must confirm you have DMG with the H3K27 alteration
This includes tumors in the spinal cord

For Arm C (patients with DMG that has grown back):

You must have Diffuse Midline Glioma or DMG that shows signs of growing or getting worse
Tissue testing must confirm you have DMG with the H3K27 alteration
You must not have received treatment for this growth yet
Your doctor must recommend re-irradiation, which means receiving radiation therapy again
You must have received focused radiation therapy as part of your first treatment
At least 6 months must have passed since your previous radiation therapy
You must have recovered from all sudden or severe side effects from previous treatments
Enough time must have passed since your last treatment: 5 half-lives for experimental drugs, 4 weeks for most chemotherapy drugs, 23 days for temozolomide, 6 weeks for nitrosoureas, 4 weeks for antibody treatments, and at least 7 days for biologic or small molecule drugs

For Arm D (patients with other returning brain tumors):

You must have a returning primary malignant CNS tumor, which is a cancer that started in your brain or spinal cord and has come back, but not a DMG
Previous tissue testing must confirm you have a malignant brain or spinal cord tumor. Patients with a tumor type called ependymoma are allowed
Your tumor must show signs of growing or getting worse
You must not have received treatment for this growth yet
If you had surgery to remove some of the growing tumor, you can still participate if the surgery was not intended to cure you completely
You must have recovered from all sudden or severe side effects from previous treatments
Enough time must have passed since your last treatment: 5 half-lives for experimental drugs, 4 weeks for most chemotherapy drugs, 23 days for temozolomide, 6 weeks for nitrosoureas, 4 weeks for antibody treatments, and at least 7 days for biologic or small molecule drugs. A drug called bevacizumab used for pseudoprogression, which is when imaging looks like the tumor is growing but it is not actually getting worse, does not require a waiting period

For Target Validation in Arms A and B:

You must be newly diagnosed with imaging scans that show you likely have DMG with the H3K27 alteration
You must have tumor tissue collected as part of your regular medical care

For Target Validation in Arms C and D:

You must have a returning primary malignant CNS tumor, including returning DMG
Your tumor must show signs of growing or getting worse
You must not have received treatment for this growth yet
You must have tumor tissue collected as part of your regular medical care

Who Cannot Join the Study?

The study information provided does not contain specific exclusion criteria, which are the reasons why a patient cannot participate in this clinical trial
Exclusion criteria are important rules that help protect patient safety and ensure the study results are accurate
These criteria typically include things like certain other medical conditions, previous treatments, laboratory test results, or medications that might interfere with the study
Without access to the complete exclusion criteria list for this trial, we cannot provide the specific reasons that would prevent participation

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht	The Netherlands

Trial status

Country	Status	Recruitment Start
The Netherlands	Recruiting	20.10.2025

Trial locations

ONC206 is an investigational medication being studied in this trial. It is given either alone or in combination with radiation therapy to treat children and young adults with brain tumors. In some parts of the trial, it is used by itself after patients have already received other treatments. In other parts, it is given together with radiation therapy for newly diagnosed patients or for patients whose tumors have come back. The study is testing different dose levels to find the safest and most effective amount to give to patients.

Focal radiation therapy is a treatment that uses high-energy rays to target and destroy cancer cells in a specific area of the brain. In this trial, it is being used together with ONC206 in some patients with newly diagnosed brain tumors. The radiation is carefully aimed at the tumor to minimize damage to surrounding healthy brain tissue.

Re-irradiation is radiation therapy given to patients who have already received radiation treatment before. In this trial, it is being combined with ONC206 for patients whose brain tumors have grown back after previous radiation treatment. This approach involves carefully delivering radiation to the tumor area again while trying to protect healthy tissue that was exposed to radiation in the past.

Investigated diseases:

Brain stem glioma

Diffuse Midline Glioma – Diffuse Midline Glioma is a type of brain tumor that develops in the midline structures of the brain, including areas such as the brainstem, thalamus, and spinal cord. This tumor is characterized by specific genetic changes, particularly alterations in the H3K27 gene. The disease most commonly affects children and young adults. The tumor grows by spreading through the normal brain tissue in these central areas. As the tumor expands, it interferes with the normal functions controlled by these critical brain regions. The progression of the disease varies depending on the exact location of the tumor within the midline structures of the central nervous system.

Recurrent Primary Malignant Central Nervous System Tumors – Recurrent primary malignant central nervous system tumors are cancerous growths that originate in the brain or spinal cord and return after initial treatment. These tumors develop from the cells of the central nervous system itself rather than spreading from other parts of the body. The disease progresses as abnormal cells multiply and form masses that can affect various parts of the brain or spinal cord. When these tumors recur, they may appear in the same location as the original tumor or in different areas of the central nervous system. The growth pattern and speed of progression can vary depending on the specific type of tumor involved. As the tumor grows, it can disrupt normal brain or spinal cord function by pressing on surrounding tissues.

Trial ID:

2025-521180-13-00

Protocol code:

PNOC023

NCT ID:

NCT04732065

Trial Phase:

Human Pharmacology (Phase I) – First administration to humans

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Study of ONC206 for children and young adults with newly diagnosed or recurrent diffuse midline glioma and other recurrent brain tumors

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?