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Study on ONC201 and Paxalisib for Children and Young Adults with Diffuse Midline Gliomas, Including Diffuse Intrinsic Pontine Gliomas

InvestigationalNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a type of brain tumor called Diffuse Midline Gliomas (DMGs), which includes a specific form known as Diffuse Intrinsic Pontine Gliomas (DIPGs). These tumors are challenging to treat and primarily affect children and young adults. The study is testing a combination of treatments to see if they can help manage these tumors more effectively. The treatments being tested include a medication called ONC201, also known by its chemical name Dordaviprone, and another medication called Paxalisib. ONC201 is a small molecule that works by blocking certain receptors in the brain, while Paxalisib is designed to inhibit specific enzymes that are involved in tumor growth.

The purpose of this study is to evaluate how well these combination therapies work in patients with DMGs. The study will be conducted in different phases, where participants will receive the combination of ONC201 and Paxalisib at various stages of their treatment journey. This includes those who are newly diagnosed, those who have completed radiation therapy, and those whose tumors have returned. The study aims to see if these treatments can help patients live longer without their disease getting worse.

Participants in the study will take the medications in capsule form, which means they will swallow them. The study will monitor the participants over time to assess the effectiveness of the treatment. The goal is to determine if the combination of ONC201 and Paxalisib can improve the outcomes for patients with these challenging brain tumors. The study is expected to continue until early 2026, with the hope of finding a more effective treatment option for those affected by DMGs and DIPGs.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, the participant will be assigned to one of the cohorts based on their specific condition and treatment history. The study involves children and young adults with a type of brain tumor called diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs).

  2. Step 2

    Treatment initiation

    Participants will begin treatment with a combination of medications. The primary medications used in this study are ONC201 and Paxalisib, both administered in capsule form. These medications are taken orally.

    The specific dosage and frequency of administration will be determined by the study protocol and the participant's assigned cohort.

  3. Step 3

    Maintenance phase

    During the maintenance phase, the combination therapy continues. The goal is to assess the effectiveness of the treatment in preventing the progression of the disease.

    For Cohorts 1 and 2, the primary measure of success is progression-free survival at 6 months, meaning the percentage of participants who are alive and whose disease has not worsened after 6 months of treatment.

    For Cohort 3, the primary measure is overall survival at 7 months, which is the percentage of participants who are alive after 7 months of treatment.

  4. Step 4

    Monitoring and assessments

    Throughout the study, participants will undergo regular monitoring and assessments to evaluate their response to the treatment and to check for any side effects.

    These assessments may include imaging tests, blood tests, and other evaluations as required by the study protocol.

  5. Step 5

    Completion of study participation

    The study is expected to continue until January 2026. Participants will complete their involvement in the study according to the timeline specified for their cohort.

    Upon completion, participants will undergo final assessments to determine the overall impact of the treatment.

Who can join the trial?

14 criteria

  • Participants must have a new diagnosis of **Diffuse Midline Glioma (DMG)**, which is a type of brain tumor, confirmed by imaging or tissue tests.
  • Participants must be between the ages of 2 and 39 years.
  • Participants must have completed radiation therapy if they are in certain groups, and must be within 4-14 weeks of finishing this therapy.
  • Participants must have evidence of tumor progression if they are in certain groups and must not have received any treatment for this progression.
  • Participants must have used **temozolomide** or **dexamethasone** during radiation therapy, which are medications used to treat cancer and reduce inflammation.
  • Participants must have stable or decreasing doses of **dexamethasone** for at least 3 days before a baseline MRI scan.
  • Participants must have adequate organ function, which includes healthy bone marrow, kidneys, liver, lungs, stomach, metabolism, and heart.
  • Participants must agree to use effective birth control methods if they are of child-bearing potential, to prevent pregnancy during the study.
  • Participants must have a performance score of at least 50, which measures their ability to perform daily activities.
  • Participants must be willing to provide a sample of their tumor tissue for study purposes.
  • Participants or their legal guardians must understand and sign a consent form to participate in the study.
  • Participants must have recovered from any side effects of previous treatments before starting the study.
  • Participants must weigh at least 10 kg to receive the study medication, **ONC201**.
  • Certain time periods must have passed since the last treatment with other medications or therapies before starting the study treatment.

Who cannot join the trial?

8 criteria

  • Patients who do not have a diagnosis of Diffuse Midline Gliomas (DMGs), including Diffuse Intrinsic Pontine Gliomas (DIPGs), cannot participate. These are specific types of brain tumors.
  • Patients who are not within the specified age range for the study cannot participate. The study is open to certain age groups only.
  • Patients who are not able to follow the study procedures or take the study medications as required cannot participate.
  • Patients who have other medical conditions that might interfere with the study or make it unsafe for them to participate cannot join the study.
  • Patients who are pregnant or breastfeeding cannot participate in the study.
  • Patients who are currently participating in another clinical trial cannot join this study.
  • Patients who have had certain treatments or medications recently that might affect the study results cannot participate.
  • Patients who have allergies or reactions to the study medications or similar drugs cannot participate.
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Investigated drugs

ONC201 is a medication being studied for its potential to treat diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs). It is being tested in combination with other novel agents to see if it can help improve the survival of children and young adults with these types of brain tumors. The trial aims to determine if this combination can slow down the progression of the disease or improve overall survival rates.

What is already known about the treatment

ONC201 – This medication is administered orally and is currently being studied in clinical trials for its potential use in treating diffuse midline gliomas, including diffuse intrinsic pontine gliomas, particularly in children and young adults. It is not yet widely established in medical practice but is gaining attention in medical literature for its promising results in early trials. The main therapeutic indication for ONC201 is its use in combination therapies aimed at improving survival rates in patients with these aggressive brain tumors. At the molecular level, ONC201 works by targeting specific pathways that promote cancer cell death and inhibit tumor growth. It is classified pharmacologically as an imipridone, a novel class of anti-cancer agents.

Investigated diseases

Diffuse Midline Gliomas – These are aggressive brain tumors that occur in the midline structures of the brain, such as the thalamus, brainstem, and spinal cord. They are characterized by their diffuse growth pattern, meaning they spread widely through the brain tissue, making them difficult to remove surgically. The progression of these tumors is typically rapid, leading to neurological symptoms depending on their location, such as difficulty with movement, balance, or speech. Diffuse Intrinsic Pontine Gliomas are a specific type of diffuse midline glioma that occur in the pons, a part of the brainstem. These tumors primarily affect children and are known for their particularly aggressive nature. As they progress, they can cause symptoms like problems with eye movements, facial weakness, and difficulty swallowing.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2023-507598-16-00Protocol codePNOC022Estimated enrolment324 patientsSponsorPrincess Maxima Center For Pediatric Oncology

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