This is an open label, intra-patient dose escalation, to evaluate ADI-PEG 20, in combination with Temozolomide (TMZ) and radiation therapy (RT) in children, adolescents and young adult patients with newly diagnosed high grade glioma (HGG).
Participants must have histologically and molecularly confirmed newly diagnosed World Health Organization (WHO) grade 3 or 4 glioma.
Phase 1: any newly diagnosed HGG (including DMG of any location and primary spinal cord tumors).
Cohort 1: Newly diagnosed non-pontine, non-spinal cord HGG histone-wildtype.
Cohort 2: Newly diagnosed non-pontine, non-spinal cord H3K27 altered diffuse midline glioma (DMG).
Participants who have received any systemic therapy or RT, including any investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20 such as pegylated compounds.
Phase 2 cohorts: tumors with epicenter in pons or spinal cord
Participants with metastatic or leptomeningeal disease. Multi-focal disease should be discussed with the study chairs,
Sequential
ADI-PEG 20 (Arginine deiminase pegylated)
DrugGiven intramuscularly (IM)
Temozolomide (TMZ)
DrugGiven orally (PO)
Standard of Care Radiation Therapy (RT)
RadiationUndergo RT
Proportion of participants with Treatment-emergent Adverse Events (TrAE) (Phase 1)
Proportion of participants in Phase 1 with treatment-emergent adverse events as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) will be reported.
Progression-Free Survival (PFS) for HGG histone-WT (Phase 2, Cohort 1)
PFS for participants in Phase 2, Cohort 1 is defined as the median number of days participants remained progression free at 12 months. Participants without a documented tumor progression or death will be censored on the date of their last evaluable tumor assessment. Participants without a documented tumor progression or death before initiation of another anti-tumor therapy will be censored on the date of their last evaluable tumor assessment prior to or on the date of the new anti-tumor therapy. PFS estimates will be obtained from the Kaplan-Meier curve. An appropriate variance term that accounts for censoring Greenwood's formula) will be used to construct the 95% confidence intervals.
Progression-Free Survival (PFS) for H3K27 altered diffuse midline glioma (DMG) (Phase 2, Cohort 2)
PFS for participants in Phase 2, Cohort 2 is defined as the median number of days participants remained progression free at 12 months. Participants without a documented tumor progression or death will be censored on the date of their last evaluable tumor assessment. Participants without a documented tumor progression or death before initiation of another anti-tumor therapy will be censored on the date of their last evaluable tumor assessment prior to or on the date of the new anti-tumor therapy. PFS estimates will be obtained from the Kaplan-Meier curve. An appropriate variance term that accounts for censoring Greenwood's formula) will be used to construct the 95% confidence intervals.
Progression-Free Survival (PFS) for H3G34 mutant diffuse hemispheric glioma (DHG) (Phase 2, Cohort 3)
PFS for participants in Phase 2, Cohort 3 is defined as the median number of days participants remained progression free at 10 months. Participants without a documented tumor progression or death will be censored on the date of their last evaluable tumor assessment. Participants without a documented tumor progression or death before initiation of another anti-tumor therapy will be censored on the date of their last evaluable tumor assessment prior to or on the date of the new anti-tumor therapy. PFS estimates will be obtained from the Kaplan-Meier curve. An appropriate variance term that accounts for censoring Greenwood's formula) will be used to construct the 95% confidence intervals.
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Sabine Mueller, MD, PhD
Lead sponsor
University of California, San Francisco
Sponsor institution
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