Ignite Creation Date:
2024-05-06 @ 3:44 PM
Last Modification Date:
2024-10-26 @ 1:55 PM
Study NCT ID:
NCT04732065
Status:
RECRUITING
Last Update Posted:
2024-04-30
First Post:
2021-01-26
Brief Title:
ONC206 for Treatment of Newly Diagnosed Recurrent Diffuse Midline Gliomas and Other Recurrent Malignant CNS Tumors
Sponsor:
Sabine Mueller MD PhD
Organization:
University of California San Francisco
Study Overview
Official Title:
PNOC023 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
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PNOC023
Brief 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
Detailed Description:
PRIMARY OBJECTIVES
I To determine the safety and tolerability of DRD2 antagonistClpP agonist ONC206 ONC206
II To determine the MTD of ONC206 as single agent in children and young adults with DMG H3K27 altered 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 H3K27 altered Arm B
IV To determine the MTD of ONC206 in combination with reirradiation in children and young adults with progression of DMG H3K27 altered Arm C
V To determine the MTD of ONC206 in children and young adults with recurrent primary malignant CNS tumors including participants with recurrent DMGs if not eligible for other arms Arm D
VI To assess the concentration of ONC206 in tumor tissue from children and young adults with DMG H3K27 altered predominantly localized to the thalamus 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 DMG H3K27 altered predominantly localized to the pons and compare to plasma drug levels pre-surgery Target validation
VIII To assess the concentration of ONC206 in tumor tissue in children and young adults with DMG H3K27 altered in non-thalamic and non-pontine locations and compare to plasma drug levels pre-surgery Target validation
IX To assess the concentration of ONC206 in tumor tissue in children and young adults with recurrent primary malignant CNS tumors and compare to plasma drug levels pre-surgery Target validation
SECONDARY OBJECTIVE
I To characterize the pharmacokinetics PK of ONC206 in plasma in patients with DMG H3K27 altered and recurrent primary malignant CNS tumorsArms A and D
EXPLORATORY OBJECTIVES
I To assess the clinical responses within the confines of a phase 1expansion study
II To assess if amount of serum circulating tumor DNA ctDNA is correlated with clinical outcome
III To assess if amount of cerebrospinal fluid CSF ctDNA is correlated with clinical outcome
IV To assess if clinical outcomes are associated with anatomic location of tumor H3K27 mutation status and other partner mutations
V To assess biomarkers of response
VI To assess the response rate to ONC206 in patients with prior ONC201 exposure
VII To assess pharmacodynamics PD of ONC206
VIII To assess PK-PD and identify the relationship between drug exposure and clinical endpoints for both safety and efficacy
IX To characterize the PK of ONC206 in CSF in patients with DMG H3K27 altered and recurrent primary malignant CNS tumors
X To assess PD changes within tumor tissue after ONC206 administration Target Validation
XI To assess microbiome and flow cytometry studies in the context of imaging and clinical outcomes using descriptive statistics
XII To assess Health Related Quality of Life HRQOL outcomes
XIII To assess patient andor proxy satisfaction with study participation via patient-reported outcome PRO measures
XIV To assess patient andor proxy satisfaction with study participation via patient-reported outcome PRO measures in the context of race ethnicity and other health related social risks
XV To assess on therapy toxicity and survival in the context of race ethnicity and other health related social risks
XVI To assess if 18F-FET-PET can support response assessment in children treated with ONC206
XVII To determine feasibility of measuring ONC206 concentrations in hair samples
XVIII To assess feasibility to obtain Proton 1H MR spectroscopy MRS with standard MRI
OUTLINE This is a dose-escalation study of ONC206 Patients are assigned to 1 of 4 arms
ARM A Children and young adults with DMG H3K27 altered who completed at least one line of prior therapy and ARM D Participants with recurrent primary malignant CNS tumors including participants with recurrent DMGs who failed at least one prior therapy including radiation therapy 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 In case the participant receives clinical benefit from the treatment treatment could possibly proceed up to 24 months
ARM B Newly diagnosed children and young adults with DMG H3K27 altered and ARM CChildren and young adults with DMG H3K27 altered who have evidence of progression but have not been treated for this progression and are candidates for re-irradiation Patients undergo standard of care radiation therapy daily 5 days a week and receive ONC206 as in Arm A
All participants will be permitted to have an optional MRS scans After completion of study treatment patients are followed up at 30 days and then every 3 months for up to 5 years
I To determine the safety and tolerability of DRD2 antagonistClpP agonist ONC206 ONC206
II To determine the MTD of ONC206 as single agent in children and young adults with DMG H3K27 altered 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 H3K27 altered Arm B
IV To determine the MTD of ONC206 in combination with reirradiation in children and young adults with progression of DMG H3K27 altered Arm C
V To determine the MTD of ONC206 in children and young adults with recurrent primary malignant CNS tumors including participants with recurrent DMGs if not eligible for other arms Arm D
VI To assess the concentration of ONC206 in tumor tissue from children and young adults with DMG H3K27 altered predominantly localized to the thalamus 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 DMG H3K27 altered predominantly localized to the pons and compare to plasma drug levels pre-surgery Target validation
VIII To assess the concentration of ONC206 in tumor tissue in children and young adults with DMG H3K27 altered in non-thalamic and non-pontine locations and compare to plasma drug levels pre-surgery Target validation
IX To assess the concentration of ONC206 in tumor tissue in children and young adults with recurrent primary malignant CNS tumors and compare to plasma drug levels pre-surgery Target validation
SECONDARY OBJECTIVE
I To characterize the pharmacokinetics PK of ONC206 in plasma in patients with DMG H3K27 altered and recurrent primary malignant CNS tumorsArms A and D
EXPLORATORY OBJECTIVES
I To assess the clinical responses within the confines of a phase 1expansion study
II To assess if amount of serum circulating tumor DNA ctDNA is correlated with clinical outcome
III To assess if amount of cerebrospinal fluid CSF ctDNA is correlated with clinical outcome
IV To assess if clinical outcomes are associated with anatomic location of tumor H3K27 mutation status and other partner mutations
V To assess biomarkers of response
VI To assess the response rate to ONC206 in patients with prior ONC201 exposure
VII To assess pharmacodynamics PD of ONC206
VIII To assess PK-PD and identify the relationship between drug exposure and clinical endpoints for both safety and efficacy
IX To characterize the PK of ONC206 in CSF in patients with DMG H3K27 altered and recurrent primary malignant CNS tumors
X To assess PD changes within tumor tissue after ONC206 administration Target Validation
XI To assess microbiome and flow cytometry studies in the context of imaging and clinical outcomes using descriptive statistics
XII To assess Health Related Quality of Life HRQOL outcomes
XIII To assess patient andor proxy satisfaction with study participation via patient-reported outcome PRO measures
XIV To assess patient andor proxy satisfaction with study participation via patient-reported outcome PRO measures in the context of race ethnicity and other health related social risks
XV To assess on therapy toxicity and survival in the context of race ethnicity and other health related social risks
XVI To assess if 18F-FET-PET can support response assessment in children treated with ONC206
XVII To determine feasibility of measuring ONC206 concentrations in hair samples
XVIII To assess feasibility to obtain Proton 1H MR spectroscopy MRS with standard MRI
OUTLINE This is a dose-escalation study of ONC206 Patients are assigned to 1 of 4 arms
ARM A Children and young adults with DMG H3K27 altered who completed at least one line of prior therapy and ARM D Participants with recurrent primary malignant CNS tumors including participants with recurrent DMGs who failed at least one prior therapy including radiation therapy 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 In case the participant receives clinical benefit from the treatment treatment could possibly proceed up to 24 months
ARM B Newly diagnosed children and young adults with DMG H3K27 altered and ARM CChildren and young adults with DMG H3K27 altered who have evidence of progression but have not been treated for this progression and are candidates for re-irradiation Patients undergo standard of care radiation therapy daily 5 days a week and receive ONC206 as in Arm A
All participants will be permitted to have an optional MRS scans After completion of study treatment patients are followed up at 30 days and then every 3 months for up to 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01CA266596 | NIH | NCI Clinical Trials Reporting Program CTRP | httpsreporternihgovquickSearchR01CA266596 |
| NCI-2021-00046 | REGISTRY | None | None |