Trials / Recruiting

RecruitingNCT06894979

Testing the Addition of an Anti-Cancer Drug, AZD1390, During Radiation Therapy for Newly Diagnosed High Grade Glioma, Diffuse Midline Glioma, or Diffuse Intrinsic Pontine Glioma

A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD1390 (NSC# 852149) When Combined With Focal Radiation in Pediatric Patients With High Grade Glioma

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 54 (estimated)

Sponsor: Children's Oncology Group · Network
Sex: All
Age: 12 Months – 22 Years
Healthy volunteers: Not accepted

Summary

This phase I clinical trial studies the side effects and best dose of AZD1390 and to see how well it works when given together with radiation therapy for the treatment of pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma. AZD1390 is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to multiply. This helps to stop the spread of cancer cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving AZD1390 with radiation may be safe, tolerable, and/or effective in treating pediatric patients with high grade glioma, diffuse midline glioma or diffuse intrinsic pontine glioma.

Detailed description

PRIMARY OBJECTIVES: I. To define the recommended phase 2 dose of ATM Kinase Inhibitor AZD1390 (AZD1390) when given in combination with radiation for pediatric supratentorial high-grade gliomas. II. To define the recommended phase 2 dose of AZD1390 when given in combination with radiation for pediatric infratentorial high-grade gliomas. III. To define the toxicities and characterize the safety profile of AZD1390 when given in combination with radiation for pediatric supratentorial high-grade gliomas. IV. To define the toxicities and characterize the safety profile of AZD1390 when given in combination with radiation for pediatric infratentorial high-grade gliomas. V. To characterize the pharmacokinetic profile of AZD1390 when given in combination with radiation to pediatric patients for pediatric supratentorial and infratentorial high-grade gliomas. SECONDARY OBJECTIVES: I. To evaluate preliminary efficacy when AZD1390 is given in combination with radiation to pediatric patients with supratentorial high-grade gliomas as determined via progression free survival (PFS), overall survival (OS) and overall radiographic response (ORR) within the confines of a phase 1 trial. II. To evaluate preliminary efficacy when AZD1390 is given in combination with radiation to pediatric patients with infratentorial high-grade gliomas as determined via PFS, OS and ORR within the confines of a phase 1 trial. III. To obtain preliminary data on neurological function of patients with supratentorial and infratentorial high-grade gliomas receiving AZD1390 and focal radiation via the pediatric neurologic assessment in neuro-oncology (NANO) scale. EXPLORATORY OBJECTIVES: I. To evaluate changes in neurocognitive function from baseline (within 2 weeks of enrollment) to end of protocol directed therapy (completion of AZD1390), at 22 weeks (5.5 months) and at 44 weeks (11.5 months) after completion of radiation. II. To evaluate changes in patient reported outcomes utilizing Patient Reported Outcomes Measurement Information System (PROMIS) from baseline (within 2 weeks of enrollment) and at the time of imaging assessments. III. To evaluate the alternative lengthening of telomeres (ALT) phenotype in archival tumor and cell-free deoxyribonucleic acid (cfDNA) in patients with high grade glioma (HGG) undergoing AZD1390 and radiation therapy. IV. To evaluate the correlation of genomic, transcriptomic, proteomic, and cytokine markers, including homologous recombination deficiency (HRD) and associated mutational signatures and TP53/related DNA repair gene mutational status, with response to AZD1390 and radiation therapy. V. Evaluate differences in radiation dosimetry to organs at risk and target volumes by radiation technique and modality and its correlation with toxicity and response and survival. VI. Evaluate cfDNA in plasma and cerebrospinal fluid (CSF) (when obtained) and pharmacodynamic markers of peripheral blood mononuclear cells (PBMCs) prior, during and after therapy to better understand its correlation with treatment response. OUTLINE: This is a dose-escalation study of AZD1390 in combination with radiation. Patients receive AZD1390 orally (PO) once within 5 days prior to radiation therapy. Patients then receive AZD1390 PO once daily (QD), 5 days per week, Monday through Friday, and also receive radiation therapy on the same days for approximately 6 weeks. Patients then receive AZD1390 on days 1-14 after radiation in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) and blood sample collection and may optionally undergo cerebrospinal fluid collection throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 8 weeks until progression or 2 years after the last dose of AZD1390 as well as at 22 and 44 weeks after completion of radiation therapy. From progression, patients are followed up will be every 6 months until year 4 from the last dose of AZD1390 then yearly until year 5.

Conditions

Interventions

Type	Name	Description
DRUG	ATM Kinase Inhibitor AZD1390	Given PO
PROCEDURE	Biospecimen Collection	Undergo blood and cerebrospinal fluid collection
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
RADIATION	Radiation Therapy	Undergo radiation therapy
OTHER	Survey Administration	Ancillary studies

Timeline

Start date: 2025-06-18
Primary completion: 2028-03-31
Completion: 2028-03-31
First posted: 2025-03-26
Last updated: 2026-03-12

Locations

17 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06894979. Inclusion in this directory is not an endorsement.