GlioblastomaPhase 1/2NCT07389278
Combination ADI-PEG 20, TMZ, and RT for Treatment of Newly Diagnosed High-grade Glioma (HGG)
A Phase 1/2 study testing ADI-PEG 20 (Arginine deiminase pegylated) and Temozolomide (TMZ) in people with Glioblastoma and High-Grade Glioma (WHO III-IV), run by Sabine Mueller, MD, PhD at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 3 to 39 years
- Conditions the study is for
- Glioblastoma, High-Grade Glioma (WHO III-IV), High-grade Glioma
- What is being tested?
- ADI-PEG 20 (Arginine deiminase pegylated) and Temozolomide (TMZ)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2027to 30 Jun 2035
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
- Phase 2:
- 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).
- Cohort 3: Newly diagnosed non-pontine, non-spinal cord H3G34 mutant diffuse hemispheric glioma (DHG).
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- Prior surgery: must have undergone maximal safe resection. For patients with DMG of the pons, biopsy is sufficient.
- Prior Therapy: Participants must NOT have received ANY prior therapy (except surgery) before enrollment on study.
- Tumor Tissue Requirement: Participants must have sufficient tumor tissue (5-10 unstained formalin-fixed paraffin-embedded (FFPE) slides or a tumor block) for study enrollment.
- Age:
- Phase 1:
- o 3 to <18 years of age.
- Phase 2:
- Cohort 1: 3 to 25 years of age.
- Cohorts 2 \& 3: 3 to 39 years of age.
- Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
- Organ Function Requirements:
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3.
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- Creatinine Clearance (CrCl) or estimated glomerular filtration rate (eGFR) with cutoff value of ≥ 60 mL/min for renal function in participants with age ≥ 18 years. For participants < 18 years old, estimate eGFR using the Schwartz equation. eGFR (mL/min/1.73 m^2) = (k × Height (cm)) / Serum Creatinine (mg/dL).
- Total bilirubin <= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN.
- alanine aminotransferase (ALT) <= 3 x ULN.
- aspartate aminotransferase (AST) <= 3 x ULN.
- Participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
- The effects of ADI-PEG 20 have been shown to be associated with embryofetal toxicity in rodents. For this reason and because chemotherapy used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
- Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.
Who cannot join
- 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,
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would interfere with the study.
- Women of childbearing potential must not be pregnant or breast-feeding.
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- Human immunodeficiency virus (HIV)-positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.
- Corrected QT Interval (QTc) cutoff >480 ms.
- Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
PNOC Operations Office, 415-502-1600, PNOC34@ucsf.edu
Sabine Mueller, MD, PhD
About this study
Official title: 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)
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).
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- 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
- Glioblastoma, High-Grade Glioma (WHO III-IV), High-grade Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Diffuse Hemispheric Glioma, H3G34 Mutant
- Being tested
- ADI-PEG 20 (Arginine deiminase pegylated), Temozolomide (TMZ), Standard of Care Radiation Therapy (RT)
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG 20 (Arginine deiminase pegylated)Drug
Also called ADI-PEG 20
Given intramuscularly (IM)
Temozolomide (TMZ)Drug
Also called TMZ
Given orally (PO)
Standard of Care Radiation Therapy (RT)Radiation
Also called RT
Undergo RT
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 (Starting Dose: ADI-PEG 20 36mg/m^2) | Experimental | Participants will receive injection of 36 mg/m^2 of ADI-PEG 20 once weekly in the concomitant phase and maintenance phases given prior to the start of RT. Participants will also receive daily oral (PO) temozolomide (TMZ) with dosage based on age and dosing phase (concomitant, then maintenance) starting on the same day as Radiotherapy (RT). RT will be given in standard fractions (total dose 59.4 Gy) over 6 weeks. The boost volume, when present, will receive an additional 5.4 Gy for a total of 59.4 Gy. Post-RT, Participants will continue to receive weekly ADI-PEG 20 as monotherapy and then proceed to first cycle of maintenance therapy 28 days (+7 days) after completion of RT, in the absence of dose-limiting toxicities (DLT) or progressive disease. The maintenance phase consists of ten cycles (28 days long) of combination chemotherapy with ADI-PEG 20 and TMZ. Participants will receive no more than 104 weeks of ADI-PEG 20 therapy Receives: Drug: Temozolomide (TMZ); Radiation: Standard of Care Radiation Therapy (RT) |
| Phase 2 (Cohort 1) - Histone Wild Type (WT) HGG | Experimental | Participants with WT HGG will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1 in combination with TMZ. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. Receives: Drug: ADI-PEG 20 (Arginine deiminase pegylated); Drug: Temozolomide (TMZ); Radiation: Standard of Care Radiation Therapy (RT) |
| Phase 2 (Cohort 2) - H3K27 Altered Diffuse Midline Gliomas (DMG) | Experimental | Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study. Receives: Drug: ADI-PEG 20 (Arginine deiminase pegylated); Drug: Temozolomide (TMZ); Radiation: Standard of Care Radiation Therapy (RT) |
| Phase 2 (Cohort 3) - H3G34 Mutant Diffuse Hemispheric Gliomas (DHG) | Experimental | Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study. Receives: Drug: ADI-PEG 20 (Arginine deiminase pegylated); Drug: Temozolomide (TMZ); Radiation: Standard of Care Radiation Therapy (RT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 104 weeks
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.
Measured: Up to 12 months
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.
Measured: Up to 12 months
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.
Measured: Up to 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study start1 Jun 2027 (estimated)
- Primary completion30 Jun 2032 (estimated)
- Study completion30 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 97 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sabine Mueller, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sabine Mueller, MD, PhD, University of California, San Francisco
- Investigators
- Sabine Mueller, MD, PhD, Principal investigator, University of California, San FranciscoTom Davidson, MD, Study chair, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389278
- Sponsor's protocol ID
- 250814
- Other IDs
- NCI-2026-00045
- Status last verified
- Sep 2026
- First submitted
- 28 Jan 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified datasets will be shared with study collaborators during the course of the study.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07389278
- Acronym / sponsor ID
- 250814
- Conditions
- Glioblastoma, High-Grade Glioma (WHO III-IV), High-grade Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Diffuse Hemispheric Glioma, H3G34 Mutant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 97 participants (estimated)
- Lead sponsor
- Sabine Mueller, MD, PhDUniversity, hospital or other
- Study start
- 1 Jun 2027 (estimated)
- Primary completion
- 30 Jun 2032 (estimated)
- Study completion
- 30 Jun 2035 (estimated)
- First posted
- 5 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1 (Starting Dose: ADI-PEG 20 36mg/m^2) | Experimental | Drug: Temozolomide (TMZ), Radiation: Standard of Care Radiation Therapy (RT)Participants will receive injection of 36 mg/m^2 of ADI-PEG 20 once weekly in the concomitant phase and maintenance phases given prior to the start of RT. Participants will also receive daily oral (PO) temozolomide (TMZ) with dosage based on age and dosing phase (concomitant, then maintenance) starting on the same day as Radiotherapy (RT). RT will be given in standard fractions (total dose 59.4 Gy) over 6 weeks. The boost volume, when present, will receive an additional 5.4 Gy for a total of 59.4 Gy. Post-RT, Participants will continue to receive weekly ADI-PEG 20 as monotherapy and then proceed to first cycle of maintenance therapy 28 days (+7 days) after completion of RT, in the absence of dose-limiting toxicities (DLT) or progressive disease. The maintenance phase consists of ten cycles (28 days long) of combination chemotherapy with ADI-PEG 20 and TMZ. Participants will receive no more than 104 weeks of ADI-PEG 20 therapy |
| Phase 2 (Cohort 1) - Histone Wild Type (WT) HGG | Experimental | Drug: ADI-PEG 20 (Arginine deiminase pegylated), Drug: Temozolomide (TMZ), Radiation: Standard of Care Radiation Therapy (RT)Participants with WT HGG will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1 in combination with TMZ. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. |
| Phase 2 (Cohort 2) - H3K27 Altered Diffuse Midline Gliomas (DMG) | Experimental | Drug: ADI-PEG 20 (Arginine deiminase pegylated), Drug: Temozolomide (TMZ), Radiation: Standard of Care Radiation Therapy (RT)Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study. |
| Phase 2 (Cohort 3) - H3G34 Mutant Diffuse Hemispheric Gliomas (DHG) | Experimental | Drug: ADI-PEG 20 (Arginine deiminase pegylated), Drug: Temozolomide (TMZ), Radiation: Standard of Care Radiation Therapy (RT)Participants will be treated at the recommended phase 2 dose (RP2D) of ADI-PEG 20 determined in Phase 1. Participants who complete the combined treatment and maintenance phase may continue receiving monotherapy treatment as extended maintenance for up to 10 additional cycles, provided there is no unacceptable toxicity, disease progression, or withdrawal of consent. ADI-PEG 20 treatment may continue for up to 104 weeks. After completing the 30-day toxicity evaluation period, participants will enter follow-up. Follow-up procedures will be documented under the PNOC COMP protocol, except for protocol-defined follow-up procedures. Participants will be followed under the PNOC COMP protocol until death or withdrawal from the study. |
Who may qualify
- Ages
- 3 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Participants must have histologically and molecularly confirmed newly diagnosed World Health Organization (WHO) grade 3 or 4 glioma.
- Prior surgery: must have undergone maximal safe resection. For patients with DMG of the pons, biopsy is sufficient.
- Prior Therapy: Participants must NOT have received ANY prior therapy (except surgery) before enrollment on study.
- Tumor Tissue Requirement: Participants must have sufficient tumor tissue (5-10 unstained formalin-fixed paraffin-embedded (FFPE) slides or a tumor block) for study enrollment.
- Age:
Key exclusion criteria (9 listed)
- 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,
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would interfere with the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADI-PEG 20 (Arginine deiminase pegylated)Also: ADI-PEG 20Given intramuscularly (IM) | Drug | Phase 2 (Cohort 1) - Histone Wild Type (WT) HGG, Phase 2 (Cohort 2) - H3K27 Altered Diffuse Midline Gliomas (DMG), Phase 2 (Cohort 3) - H3G34 Mutant Diffuse Hemispheric Gliomas (DHG) |
| Temozolomide (TMZ)Also: TMZGiven orally (PO) | Drug | Phase 1 (Starting Dose: ADI-PEG 20 36mg/m^2), Phase 2 (Cohort 1) - Histone Wild Type (WT) HGG, Phase 2 (Cohort 2) - H3K27 Altered Diffuse Midline Gliomas (DMG), Phase 2 (Cohort 3) - H3G34 Mutant Diffuse Hemispheric Gliomas (DHG) |
| Standard of Care Radiation Therapy (RT)Also: RTUndergo RT | Radiation | Phase 1 (Starting Dose: ADI-PEG 20 36mg/m^2), Phase 2 (Cohort 1) - Histone Wild Type (WT) HGG, Phase 2 (Cohort 2) - H3K27 Altered Diffuse Midline Gliomas (DMG), Phase 2 (Cohort 3) - H3G34 Mutant Diffuse Hemispheric Gliomas (DHG) |
Primary outcome
Proportion of participants with Treatment-emergent Adverse Events (TrAE) (Phase 1)
Time frame: Up to 104 weeks
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)
Time frame: Up to 12 months
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)
Time frame: Up to 12 months
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)
Time frame: Up to 10 months
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified datasets will be shared with study collaborators during the course of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sabine Mueller, MD, PhD principal investigator
University of California, San Francisco
Tom Davidson, MD study chair
Children's Hospital Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ADI-PEG 20 (Arginine deiminase pegylated) and Temozolomide (TMZ) in people with Glioblastoma and High-Grade Glioma (WHO III-IV), run by Sabine Mueller, MD, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact PNOC Operations Office (415-502-1600, PNOC034@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with Treatment-emergent Adverse Events (TrAE) (Phase 1) (time frame: Up to 104 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.