What side effects are associated with this type of intervention?

Common treatments for Diffuse Midline Glioma include radiation therapy, chemotherapy (such as temozolomide), and experimental drugs like ONC206 that induce a stress response in tumor cells. Known side effects of these treatments can include fatigue, nausea, headaches, and skin reactions from radiation. Chemotherapy may cause additional side effects such as bone marrow suppression, leading to anemia, increased risk of infection, and bleeding. Experimental treatments like ONC206, which target tumor cell stress responses, may also cause specific side effects related to the stress pathways they activate, but detailed side effect profiles are still under investigation.

What prior FDA approvals exist?

There have been no specific FDA approvals for drugs targeting Diffuse Midline Glioma that work by inducing a stress response in tumor cells leading to cell death, similar to ONC206. However, treatments for other types of gliomas, such as temozolomide, have been approved and are commonly used. Temozolomide works by damaging the DNA of cancer cells, which can lead to cell death, though its mechanism is not specifically through inducing a stress response.

What other types of research exist?

Promising alternatives to ONC206 for Diffuse Midline Glioma patients include: 1) Temozolomide, which has shown efficacy in various CNS tumors, including gliomas. 2) Bevacizumab, an anti-VEGF antibody that has been used in recurrent gliomas. 3) Everolimus, an mTOR inhibitor that has shown activity in aggressive CNS tumors. 4) Nivolumab, a PD-1 inhibitor that has demonstrated responses in various CNS malignancies. These treatments offer different mechanisms of action and have shown potential in clinical settings.

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Stress Response Inducer

ONC206 + Radiation Therapy for Brain Tumor (PNOC023 Trial)

Phase 1

Recruiting

Research Sponsored by Sabine Mueller, MD, PhD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS tumors, including recurrent DMG, who have evidence of progression but have not been treated for this progression

Serum creatinine < 1.5 Upper Limit normal (ULN) based on age and gender

Must not have

Participants with a known disorder that affects their immune system, such as HIV, hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy

Participants with uncontrolled infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), day 3 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), (2 days in total)

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effects of ONC206, a new drug that stresses out cancer cells to kill them, in children and young adults with difficult-to-treat brain tumors. The drug can be used alone or with radiation therapy. ONC206 is related to ONC201, which has shown promise in treating certain types of brain tumors.

Who is the study for?

This trial is for children and adults with newly diagnosed or recurrent diffuse midline gliomas (DMG) and other malignant CNS tumors. Participants must have stable vital signs, not be pregnant or breastfeeding, agree to use contraception if applicable, and cannot be on certain medications that affect ONC206 absorption or immune system disorders.

What is being tested?

The trial is testing the effectiveness of a new drug called ONC206 alone or combined with standard radiation therapy. The goal is to find the best dose that can stop tumor growth by triggering a stress response in cancer cells without harming normal cells.

What are the potential side effects?

Potential side effects of ONC206 are not detailed here but may include reactions related to the body's stress response to treatment. Standard radiation therapy side effects typically include fatigue, skin irritation at the treatment site, and potential hair loss.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My child has a recurring brain tumor that has progressed but hasn't been treated for this progression.

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My kidney function, measured by creatinine, is within the normal range for my age and gender.

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I am newly diagnosed with a specific brain tumor showing certain genetic changes.

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I am willing to provide tissue samples for the study.

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My previous tests confirmed I have a malignant brain tumor.

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My tumor is confirmed as DMG, H3K27 altered by a pathology test.

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My tumor is confirmed to have a specific genetic change known as DMG, H3K27 altered.

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I am a young person newly diagnosed with a specific brain or spinal tumor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an immune system disorder like HIV, hepatitis B or C, or an autoimmune disease.

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I do not have any infections that are currently uncontrolled.

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I haven't taken strong enzyme affecting drugs for 14 days and won't during the study.

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I am pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), day 3 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), (2 days in total)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), day 3 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), (2 days in total)

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), day 3 (pre-dose, 0.5, 1, 2, 4, 8 post-dose), (2 days in total) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) of ONC206

Proportion of participants with dose-limiting toxicities (DLT)

Secondary study objectives

Area under the curve (AUC) of ONC206

Elimination half-life (t1/2) of ONC206

Mean Total body clearance (CL) for ONC206

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm D: ONC206 Therapy, Primary malignant CNS tumors with progressionExperimental Treatment2 Interventions

Patients receive ONC206 PO once a day (QD) up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Group II: Arm C: ONC206 + radiation therapy, DMGs with evidence of first progression but previously untreatedExperimental Treatment3 Interventions

Patients undergo standard of care radiation therapy daily 5 days a week and receive ONC206 PO up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Group III: Arm B: ONC206 + radiation therapy for newly diagnosed participantsExperimental Treatment3 Interventions

Group IV: Arm A: ONC206 for participants with diffuse midline gliomas + prior therapyExperimental Treatment2 Interventions

Patients receive ONC206 orally (PO) up to six times per week. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Diffuse Midline Glioma include radiation therapy and emerging targeted therapies like ONC206. Radiation therapy works by damaging the DNA of cancer cells, leading to cell death and slowing tumor growth. ONC206, a novel compound, induces a stress response in tumor cells, causing them to die without affecting normal cells. This mechanism is crucial for Diffuse Midline Glioma patients as it offers a targeted approach that minimizes damage to healthy brain tissue, potentially improving outcomes and reducing side effects compared to traditional therapies.