Trials / Not Yet Recruiting

Not Yet RecruitingNCT07389278

Combination ADI-PEG 20, TMZ, and RT for Treatment of Newly Diagnosed High-grade Glioma (HGG)

A Phase 1/2 Study of Pegylated Arginine Deiminase (ADI-PEG 20) Plus Radiotherapy (RT) and Temozolomide (TMZ) in Children, Adolescents, and Young Adults With Newly Diagnosed High-grade Glioma (HGG)

Status: Not Yet Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 97 (estimated)

Sponsor: Sabine Mueller, MD, PhD · Academic / Other
Sex: All
Age: 3 Years – 39 Years
Healthy volunteers: Not accepted

Summary

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).

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and estimate the RP2D of ADI-PEG 20 in combination with RT and TMZ in with children, adolescents, and young adults with newly diagnosed high-grade glioma, and the RP2D of ADI-PEG 20 during maintenance therapy with TMZ (Phase 1) II. To assess the anti-tumor activity of the combination of ADI-PEG 20 with RT and TMZ based on progression-free survival (PFS) at 12 months for HGG histone-WT participants, 12 months for H3K27 altered DMG, and 10 months for H3G34 mutant DHG in children, adolescents, and young adult participants (Phase 2) EXPLORATORY OBJECTIVES: I. To assess the anti-tumor activity of the combination of ADI-PEG 20 with RT and TMZ based on overall survival at 12 months for HGG histone-WT, Histone 3 lysine 27 (H3K27) altered DMG, and Histone 3 G34-mutant (H3G34) DHGs. II. To correlate argininosuccinate synthase 1 (ASS1) and arginase tumor expression and Cerebral spinal fluid (CSF)/systemic arginine levels with survival. III. To correlate levels of cell free DNA and other liquid biomarkers in the context of imaging response criteria and clinical outcome. IV. To assess the microbiome in the context of imaging response criteria and clinical outcome. V. To describe the pharmacokinetics of ADI-PEG 20 in combination with radiotherapy and TMZ and in maintenance treatment in children, adolescent and young adults with HGG. VI. To describe the pharmacodynamics of ADI-PEG 20 in combination with radiotherapy and TMZ and in maintenance treatment in children, adolescent and young adults with HGG. VII. To assess immunogenicity of ADI-PEG 20 in combination with radiotherapy and TMZ and in maintenance treatment in children, adolescent and young adults with HGG. VIII. To explore the use of serial single voxel magnetic resonance (MR) spectroscopy to evaluate on-target tumor metabolic changes with the use of ADI-PEG 20. IX. To explore sex differences in arginine metabolism in participants with newly diagnosed high-grade glioma pre and post treatment with ADI-PEG 20. X. To characterize immune micro-environment of tumor edge in comparison to tumor core. Inclusion of normal/reactive brain tissue will be used to compare baseline reactive transcriptional signature, including immune pathways activated in peritumoral regions of the brain. OUTLINE: Participants will be enrolled into Phase 1 (dose escalation) where the pediatric RP2D of ADI-PEG 20 in combination with radiotherapy and daily TMZ (DLT period 1) as well as ADI-PEG 20 with TMZ during maintenance (DLT period 2) will be determined through a rolling-6 design and then followed by a planned Phase 2. Participants in Phase 2 will further be analyzed by cohort based on confirmed diagnosis of the following expressed biomarkers: Cohort 1: Participants with newly diagnosed histone wild type (WT) HGG. (N=25). Cohort 2: Participants with newly diagnosed H3K27 altered diffuse midline gliomas (DMG). (N=30). Cohort 3: Participants with newly diagnosed H3G34 mutant diffuse hemispheric gliomas (DHG). (N=18). Participants can receive treatment up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up and additional follow-up data will be documented under the Pediatric Neuro-oncology Consortium (PNOC) COMP protocol. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study.

Conditions

Interventions

Type	Name	Description
DRUG	ADI-PEG 20 (Arginine deiminase pegylated)	Given intramuscularly (IM)
DRUG	Temozolomide (TMZ)	Given orally (PO)
RADIATION	Standard of Care Radiation Therapy (RT)	Undergo RT

Timeline

Start date: 2026-03-09
Primary completion: 2032-06-30
Completion: 2035-06-30
First posted: 2026-02-05
Last updated: 2026-02-05

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT07389278. Inclusion in this directory is not an endorsement.