Recruitment

Recruitment Status
Not yet recruiting
Estimated Enrollment
Same as current

Summary

Conditions
  • Diffuse Midline Glioma (DMG)
  • Glioblastoma
  • Malignant Brain Tumors
  • Recurrent Ependymoma
  • Recurrent Malignant Brain Neoplasm
  • Spinal Cord Glioma
  • WHO Grade III Glioma
Type
Interventional
Phase
Phase 1
Design
Allocation: Non-RandomizedIntervention Model: Parallel AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 2 years and 21 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of DRD2 antagonist/ClpP agonist ONC206 (ONC206). II. To determine the maximum tolerated dose (MTD) of ONC206 as single agent in children and young adults with diffuse midline glioma (DMG) who completed at least one line of prior therapy...

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of DRD2 antagonist/ClpP agonist ONC206 (ONC206). II. To determine the maximum tolerated dose (MTD) of ONC206 as single agent in children and young adults with diffuse midline glioma (DMG) who completed at least one line of prior therapy that included focal radiation therapy. (Arm A). III. To determine the MTD of ONC206 in combination with focal radiation therapy in newly diagnosed children and young adults with DMG. (Arm B). IV. To determine the MTD of ONC206 in combination with re-irradiation in children and young adults with first progression of DMG. (Arm C). V. To determine the MTD of ONC206 in children and young adults with recurrent primary malignant brain tumors including participants with recurrent DMGs if they are not eligible for the other arms. (Arm D). VI. To assess the concentration of ONC206 in tumor tissue from children and young adults with DMG and compare to plasma drug levels pre-surgery. (Target validation). VII. To assess the concentration of ONC206 in tumor tissue in children and young adults with recurrent primary malignant brain tumors and compare to plasma drug levels pre-surgery. (Target validation). SECONDARY OBJECTIVE: I. To describe the pharmacokinetics associated with ONC206 without radiation therapy. (Arms A and D). EXPLORATORY OBJECTIVES: I. Determine changes in cranial nerve scoring. II. Determine clinical responses within the confines of a phase 1/expansion study. III. Evaluate correlation of amount of serum and cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) with clinical outcome. IV. Evaluate association of clinical outcomes with anatomic location of tumor, H3K27 mutation status and other partner mutations. V. Pharmacodynamic (PD) effects in tumor tissue. VI. Assess the overall response rate to ONC206 in patients with prior ONC201 exposure. VII. Assess pharmacodynamics (PD) of ONC206 and perform exploratory pharmacokinetic (PK)-PD analyses to investigate and identify the relationship between drug exposure and clinical endpoints for both safety and efficacy. VIII. To assess Health Related Quality of Life (HRQOL) outcomes. VIIII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures OUTLINE: This is a dose-escalation study of ONC206. Patients are assigned to 1 of 4 arms. ARMS A and D: Patients receive ONC206 orally (PO) once daily (QD) on days 1, 8, 15, 22. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. ARMS B and C: Patients undergo standard of care radiation therapy daily 5 days a week and receive ONC206 as in Arm A. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 5 years.

Tracking Information

NCT #
NCT04732065
Collaborators
  • Chimerix
  • Mithil Prasad Foundation
  • Storm the Heavens Fund
  • The ChadTough Defeat DIPG Foundation
Investigators
Study Chair: Sabine Mueller, MD, PhD University of California, San Francisco