Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors
Sabine Mueller, MD, PhD
Summary
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.
Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of bitopic dopamine receptor D2 (DRD2) antagonist/human Caseinolytic protease P (ClpP) agonist ONC206 (ONC206) as single agent in children and young adults with diffuse midline glioma (DMG), Histone 3 lysine 27 (H3K27) altered, who completed at least one line of prior therapy that included focal radiation therapy. (Arm A). II. To determine the MTD of ONC206 in combination with focal radiation therapy in newly diagnosed children and young adults with DMG, H3K27 altered (Arm B). III. To determine the MTD of ONC206 in combina…
Eligibility
- Age range
- 2–21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 pat…
Interventions
- DrugONC206
Given orally (PO)
- RadiationStandard of Care Radiation Therapy
Undergo RT
- ProcedureOptional Proton (1H) MR spectroscopy (MRS)
Optional imaging procedure
Locations (6)
- University of California, San FranciscoSan Francisco, California
- Emory UniversityAtlanta, Georgia
- University of MichiganAnn Arbor, Michigan
- Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania
- Princess Máxima Center for Pediatric OncologyUtrecht
- The University Children's Hospital in ZurichZurich, Canton of Zurich