ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors

Recruiting now · Phase 1

Conditions studied: Diffuse Midline Glioma (DMG), Glioblastoma, Recurrent Ependymoma, Recurrent Malignant Central Nervous System Neoplasm, Spinal Cord Glioma, World Health Organization (WHO) Grade III Glioma, CNS Tumor, Central Nervous System Tumor

In brief

This phase I trial studies the effects and best dose of ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors. ONC206 is a recently discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called "stress response" in tumor cells. This stress response causes cancer cells to die, but without affecting normal cells. ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors.

Key facts

Study ID

NCT04732065

Run by

Sabine Mueller, MD, PhD

People needed

208

Starts

2021-08-23

Expected to finish

2027-07-31

Last updated by the study team

2026-06-11

Who can join

Age: 2 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who completed at least one line of prior therapy. Prior treatment must have included focal radiation therapy and patients must be within 4-14 weeks from completion of radiation therapy to registration (patients must start treatment within 1 week from registration), have not started any other therapies post-radiation, and have no evidence of disease progression.
• ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology must be consistent with a DMG, H3K27 altered.
• ARM A: Participants must have recovered from all acute side effects of prior therapy.
• ARM A: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)
• ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) with a diagnosis of DMG, H3K27 altered are eligible, including spinal cord DMGs.
• ARM B: Tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG, H3K27 altered.
• ARM C: Children and young adults with DMGs (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression and are recommended to get re-irradiation.
• ARM C: Patients must have undergone prior focal radiation therapy as part of their initial therapy and should be at least 6 months from prior radiation therapy. If timing is less than 6 months from prior focal radiation, these patients need to be discussed with the study chair(s).
• ARM C: Tumor tissue confirmation is mandatory and pathology must be consistent with a DMG, H3K27 altered.
• ARM C: Participants must have recovered from all acute side effects of prior therapy
• ARM C: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)
• ARM D: Children and young adults with recurrent primary malignant CNS tumors, excluding DMGs, (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression. Participants who received a surgical resection for that progression are eligible if surgery has no curative intent. These patients need to be discussed with the study team.
• ARM D: Prior tumor tissue confirmation is mandatory and pathology from the primary tumor must be consistent with malignant CNS tumor (diagnosis of ependymoma is allowed).Tissue at the time of progression is not required.
• ARM D: Participants must have recovered from all acute side effects of prior therapy
• ARM D: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team). Bevacizumab used for pseudoprogression does not require a wash out period.
• TARGET VALIDATION: Newly diagnosed children and adults (2 years of age and above) with imaging consistent with a DMG, H3K27 altered are eligible.
• TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS tumors, including recurrent DMG, (2 years of age and above) who have evidence of progression but have not been treated for this progression.
• TARGET VALIDATION: Participants must undergo tumor tissue collection as part of their standard of care
• Participants who are receiving steroids must be on a stable or decreasing dose for at least 3 days prior to registration.
• Peripheral absolute neutrophil count (ANC) >= neutrophil 1.0 g/l.
• Platelet count >= 100 x 10\^9/L (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• Serum creatinine < 1.5 Upper Limit normal (ULN) based on age and gender.
• Total bilirubin <= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN.
• Alanine aminotransferase (ALT) <= 3 x ULN.
• Aspartate aminotransferase (AST) <= 3 x ULN.

You may not qualify if…

• Arm A \& B: For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply: Thalamic DMG and cerebellar, H3K27 altered that has undergone standard radiation without concurrent therapy (other than temozolomide).
• Arm C \& D: Patients who participated in trials investigating ONC201 in the upfront setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or expanded access programs will be allowed.
• Participants who are currently receiving another investigational drug are not eligible.
• Participants who are currently receiving other anti-cancer agents are not eligible.
• Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.
• Participants with uncontrolled infection.
• Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy.
• Active illicit drug use or diagnosis of alcoholism.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant or family.
• Any participants with illnesses that may affect absorption of ONC206.
• Any participants on strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 at least 14 days prior and throughout the study.

Where it is running

• University of California, San Francisco — San Francisco, California, United States (enrolling)
• Children's National Hospital — Washington D.C., District of Columbia, United States (enrolling)
• Emory University — Atlanta, Georgia, United States (enrolling)
• University of Michigan — Ann Arbor, Michigan, United States (enrolling)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
• Princess Máxima Center for Pediatric Oncology — Utrecht, Netherlands (enrolling)
• The University Children's Hospital in Zurich — Zurich, Canton of Zurich, Switzerland (enrolling)

Full record on ClinicalTrials.gov

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