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Study on ONC201 and Everolimus with Radiotherapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Other Diffuse Midline Gliomas in Children, Adolescents, and Adults

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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 Intrinsic Pontine Glioma (DIPG) and other similar tumors known as Diffuse Midline Gliomas that have specific genetic changes, such as the H3K28M mutation or are EZHIP positive. These tumors are challenging to treat and primarily affect children, adolescents, and adults. The study aims to evaluate the effectiveness of a medication called ONC201 compared to another medication, everolimus, when used alongside radiotherapy. Radiotherapy is a treatment that uses high-energy rays to target and kill cancer cells.

Participants in the study will receive either ONC201 or everolimus in combination with radiotherapy. ONC201 is a capsule, while everolimus is available in tablet form under the brand names Afinitor and Votubia. The study will monitor how long patients live without the disease getting worse, which is known as progression-free survival. The trial will also assess the safety of the treatments and any side effects that may occur during the study period.

The study will follow participants over time to gather information on how well the treatments work and their safety. This information will help determine the best treatment options for patients with these types of brain tumors. The trial is expected to continue until 2031, providing valuable insights into the management of DIPG and related tumors.

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, an informed consent form must be signed. This form confirms understanding of the study and agreement to participate. If underage, a parent or legal representative must also sign.

    A series of initial tests will be conducted to confirm eligibility. These tests include a review of medical history, physical examination, and specific laboratory tests.

  2. Step 2

    Randomization

    Participants will be randomly assigned to one of two groups. One group will receive the medication everolimus in combination with radiotherapy, while the other group will receive a different medication called ONC201 with radiotherapy.

    Randomization ensures that each participant has an equal chance of being assigned to either group, which helps in comparing the effectiveness of the treatments.

  3. Step 3

    Treatment phase

    If assigned to the everolimus group, the medication will be taken orally. The dosage and frequency will be determined by the study team based on individual needs and responses.

    Radiotherapy will be administered as part of the treatment plan. The schedule and duration will be explained by the healthcare provider.

  4. Step 4

    Monitoring and follow-up

    Regular follow-up appointments will be scheduled to monitor health and response to treatment. These appointments may include physical exams, imaging tests, and laboratory tests.

    Participants will be asked to report any side effects or changes in health during the study. This information is crucial for assessing the safety and effectiveness of the treatment.

  5. Step 5

    End of study participation

    At the end of the study, a final evaluation will be conducted. This may include a comprehensive health assessment and discussion of the study's findings.

    Participants will receive information about any further treatment options or follow-up care needed after the study concludes.

Who can join the trial?

19 criteria

  • Diagnosis of DIPG (Diffuse Intrinsic Pontine Glioma) confirmed by clinical and radiological methods. If a biopsy (a small sample of tissue) is needed, informed consent is required.
  • Written informed consent from parents or legal representatives, and the patient, with age-appropriate agreement, must be obtained before any study procedures.
  • Participants must be enrolled in the BIOMEDE 2.0 study.
  • Life expectancy should be more than 12 weeks after starting the study treatment.
  • Histological diagnosis (tissue examination) of DIPG confirmed by central pathology review, or typical radiology of a DIPG with a short clinical history (less than three months of symptoms) if no histological confirmation is available.
  • Histological diagnosis of ND-DMG (Non-DIPG Diffuse Midline Glioma) confirmed by central pathology review, with specific genetic mutations or protein changes.
  • Performance status (ability to perform daily activities) should be above 50% on specific scales, not considering neurological deficits caused by the tumor.
  • Effective contraception is required for patients of reproductive potential during the study and for 6 months after treatment ends.
  • Negative pregnancy test for females of reproductive potential within one week before randomization.
  • Blood tests must show adequate levels of neutrophils (a type of white blood cell) and platelets (cells that help with blood clotting).
  • Liver function tests must be within normal limits.
  • Kidney function tests must be within normal limits, or creatinine clearance (a measure of kidney function) must be above a certain level.
  • Normal blood clotting tests within local reference ranges.
  • Eligible for a biopsy, or biopsy material must be available for biomarker assessment (testing for specific biological markers).
  • Age must be over 6 months, with no upper age limit. Children between 6 months and 3 years will be considered individually for inclusion.
  • Eligible for brain or spinal radiotherapy (a type of cancer treatment using radiation).
  • No prior chemotherapy or brain radiation therapy for the current cancer. Surgery is allowed if done for diagnosis or treatment.
  • Metastatic disease (cancer that has spread) or spinal tumors are allowed. In these cases, radiotherapy will be given first, and medical treatment will start after radiotherapy ends.
  • Participants must be affiliated with a social security system or be a beneficiary according to local requirements.

Who cannot join the trial?

5 criteria

  • Patients who have not been newly diagnosed with diffuse intrinsic pontine glioma or other diffuse midline gliomas that are H3K28M mutant or EZHIP positive cannot participate. These are specific types of brain tumors.
  • Patients who are not within the age range specified for the study cannot participate. The study includes children, adolescents, and adults.
  • Patients who are not able to undergo the required combination of treatments, which includes the study drug ONC201, another drug called everolimus, and radiotherapy (a treatment using radiation), cannot participate.
  • Patients who have any other medical conditions that might interfere with the study treatments or affect their safety cannot participate.
  • Patients who are unable to follow the study procedures or attend the required visits cannot participate.
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Investigated drugs

  • ONC201

    is a medication being studied for its potential to treat a type of brain tumor called Diffuse Intrinsic Pontine Glioma (DIPG) and other similar tumors. It works by targeting specific pathways in cancer cells, which may help to stop the tumor from growing or spreading. This medication is being tested to see if it can improve the time patients live without the disease getting worse.

  • Everolimus

    is a medication that is already used to treat some types of cancer. It works by blocking a protein that helps cancer cells grow and divide. In this trial, everolimus is being combined with radiotherapy to see if it can help improve outcomes for patients with newly diagnosed brain tumors, specifically those with certain genetic mutations. The goal is to see if this combination can help patients live longer without their disease progressing.

What is already known about the treatment

  • ONC201

    ONC201 is administered orally and is currently being studied in clinical trials for its potential to treat certain brain tumors, specifically diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas with specific genetic mutations. It is being evaluated for its effectiveness in combination with radiotherapy. The medication works by targeting specific pathways in cancer cells, leading to their death, and is classified as a small molecule inhibitor. Its main therapeutic use is aimed at improving progression-free survival in patients with these aggressive brain tumors.

  • Everolimus

    Everolimus is taken orally and is a well-established medication in the medical field, often used to treat various types of cancer and other conditions. In the context of this clinical trial, it is being tested in combination with radiotherapy for its effectiveness against newly diagnosed diffuse midline gliomas, including DIPG. Everolimus works by inhibiting a protein that helps cancer cells grow and divide, and it is classified as an mTOR inhibitor. The main goal is to assess its ability to prolong the time patients live without their disease worsening.

Investigated diseases

  • Diffuse Intrinsic Pontine Glioma (DIPG)

    This is a type of brain tumor that occurs in the pons, a part of the brainstem. It primarily affects children and is characterized by its diffuse growth pattern, meaning it spreads widely through the brain tissue. The tumor cells infiltrate the normal brain tissue, making it difficult to remove surgically. As the disease progresses, it can cause symptoms such as difficulty with balance and coordination, problems with eye movements, and facial weakness. Over time, these symptoms can worsen as the tumor grows and affects more areas of the brainstem. DIPG is known for its aggressive nature and rapid progression.

  • Diffuse Midline Glioma, H3K28M Mutant

    This is a type of brain tumor that occurs in the midline structures of the brain, such as the thalamus, brainstem, or spinal cord. It is characterized by a specific genetic mutation known as H3K28M, which affects the histone proteins involved in DNA packaging. This mutation leads to changes in gene expression that promote tumor growth. The tumor tends to grow diffusely, infiltrating surrounding brain tissue, which complicates surgical removal. As the disease progresses, it can cause neurological symptoms depending on its location, such as motor dysfunction, sensory changes, or cognitive impairments. The progression is typically aggressive, with symptoms worsening as the tumor expands.

  • Diffuse Midline Glioma, EZHIP Positive

    This is a type of brain tumor found in the midline regions of the brain, including the thalamus and brainstem. It is characterized by the presence of the EZHIP protein, which is associated with changes in gene expression that drive tumor growth. The tumor grows diffusely, spreading through the brain tissue and making surgical removal challenging. As it progresses, it can lead to symptoms such as headaches, nausea, and neurological deficits depending on its location. The disease tends to progress rapidly, with increasing severity of symptoms as the tumor enlarges. The diffuse nature of the tumor contributes to its aggressive progression.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-506027-29-00Protocol codeCSET 2014/2126Estimated enrolment474 patientsSponsorInstitut Gustave Roussy

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