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

NCT06894979 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2415NCI-2025-01429UM1CA228823
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Childhood Astrocytoma; Childhood Diffuse Intrinsic Pontine Glioma; Childhood Diffuse Midline Glioma; Childhood Glioblastoma; Childhood Malignant Glioma

Outcome Measures

Primary Outcomes (9)

• Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ATM Kinase Inhibitor AZD1390 (AZD1390) for pediatric supratentorial high-grade gliomas

  The maximum tolerated dose or recommended phase 2 dose will be estimated by the isotonic estimates of toxicity probabilities for which the estimate of the DLT/RP2D rate is closed to the target rate of 25% in children and adolescents with supratentorial tumors.

  Up to 75 days

• Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AZD1390 for pediatric infratentorial high-grade gliomas

  The maximum tolerated dose or recommended phase 2 dose will be estimated by the isotonic estimates of toxicity probabilities for which the estimate of the DLT/RP2D rate is closed to the target rate of 25% in children and adolescents with infratentorial tumors.

  Up to 75 days

• Incidence of adverse events for AZD1390 for pediatric supratentorial high-grade gliomas

  Frequency (%) of evaluable patients with toxicity at least possibly attributable to study agent stratified by study part and dose level using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).

  Up to 5 years

• Incidence of adverse events for AZD1390 for pediatric infratentorial high-grade gliomas

  Frequency (%) of evaluable patients with toxicity at least possibly attributable to study agent stratified by study part and dose level using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).

  Up to 5 years

• Maximum serum concentration of AZD1390

  Median (min, max) of the maximum serum concentration of AZD1390 assessed at time 0, 2, 4, 6, 8, and 24-hours post dose on cycle 1 day 1.

  Up to 24 hours

• Time to peak drug concentration of AZD1390

  Median (min, max) of the time to peak drug concentration of AZD1390 assessed at time 0, 2, 4, 6, 8, and 24-hours post dose on cycle 1 day 1.

  Up to 24 hours

• Elimination half-life of AZD1390

  Median (min, max) of the elimination half-life of AZD1390 assessed at time 0, 2, 4, 6, 8, and 24-hours post dose on cycle 1 day 1.

  Up to 24 hours

• Clearance of AZD1390

  Median (min, max) of the clearance of AZD1390 assessed at time 0, 2, 4, 6, 8, and 24-hours post dose on cycle 1 day 1.

  Up to 24 hours

• Volume of distribution of AZD1390

  Median (min, max) of the volume of distribution of AZD1390 assessed at time 0, 2, 4, 6, 8, and 24-hours post dose on cycle 1 day 1.

  Up to 24 hours

Secondary Outcomes (7)

• Progression free survival (PFS) for patients with supratentorial high-grade gliomas

  Up to 5 years

• Overall survival (OS) for patients with supratentorial high-grade gliomas

  Up to 5 years

• Overall radiographic response (ORR) for patients with supratentorial high-grade gliomas

  Up to 5 years

• PFS for patients with infratentorial high-grade gliomas

  Up to 5 years

• OS for patients with infratentorial high-grade gliomas

  Up to 5 years

Other Outcomes (6)

• Change in Neurocognitive function

  Up to 44-weeks

• Change in patient reported outcomes measurement information system

  Up to 5 years

• Alternative lengthening of telomeres phenotype

  Up to 5 days

Study Arms (1)

Treatment (AZD1390 and radiation therapy)

EXPERIMENTAL

Patients receive AZD1390 PO once within 5 days prior to radiation therapy. Patients then receive AZD1390 PO 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 MRI and blood sample collection and may optionally undergo cerebrospinal fluid collection throughout the study.

Drug: ATM Kinase Inhibitor AZD1390; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Other: Survey Administration

Interventions

ATM Kinase Inhibitor AZD1390 DRUG

Given PO

Also known as: AZD-1390, AZD1390

Treatment (AZD1390 and radiation therapy)

Biospecimen Collection PROCEDURE

Undergo blood and cerebrospinal fluid collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (AZD1390 and radiation therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (AZD1390 and radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (AZD1390 and radiation therapy)

Survey Administration OTHER

Ancillary studies

Treatment (AZD1390 and radiation therapy)

Eligibility Criteria

• Age: 12 Months - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• COHORT A and COHORT B: For the dose escalation phase, patients must be ≥ 12 months and \< 18 years of age at the time of study enrollment
• COHORT C and COHORT D: For the disease expansion phase, patients must be ≥ 12 months and \< 22 years of age at the time of study enrollment
• Patients with newly diagnosed primary high-grade glioma (HGG), diffuse midline glioma (DMG) (excluding primary spinal tumors), or diffuse intrinsic pontine glioma (DIPG) who are eligible to receive 54-59.4 grey (Gy) fractionated radiation at 1.8 Gy/day. Patients must have had histologic verification of malignancy at original diagnosis except in patients with DIPG as defined below.
• COHORTS A AND C (SUPRATENTORIAL TUMORS):
• HGG and non-pontine DMG:
• Patients with newly diagnosed HGG (including diffuse hemispheric glioma, H3 G34-mutant; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; astrocytoma; IDH-mutant; or glioblastoma, IDH-wildtype): or non-pontine DMG (including diffuse midline glioma, H3 K27-altered; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; astrocytoma; IDH-mutant; or glioblastoma, IDH-wildtype) require histologic diagnosis.
• COHORT B AND D (INFRATENTORIAL TUMORS):
• DIPG/pontine DMG or infratentorial HGG or DMG:
• Patients with newly diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required.
• Patients with infratentorial tumors that do not meet radiographic criteria for typical DIPG (e.g., focal tumors or those involving less than 2/3 of the pontine cross-sectional area with or without extrapontine extension) are eligible if the tumors are biopsied and proven to be high-grade gliomas (including diffuse midline glioma H3 K27-altered; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; astrocytoma; IDH-mutant; or glioblastoma, IDH-wildtype) by institutional diagnosis.
• Protocol Definitions
• Supratentorial tumors are defined as tumors with an epicenter in the cerebral hemispheres, basal ganglia, thalamus, hypothalamus, or pituitary gland.
• Infratentorial tumors are defined as tumors with an epicenter in the brainstem, cerebellum
• Patients with measurable or non-measurable (following a gross total resection) disease
• Karnofsky ≥ 50% for patients \> 16 year of age and Lansky ≥ 50% for patients ≤ 16 years of age.

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of childbearing potential should use adequate contraception during study participation and for 6 months after the last dose of AZD1390. Male patients with female partners of childbearing potential should use adequate contraception during study participation and for 16 weeks after the last dose of AZD1390
• Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible with the exception of corticosteroids
• Anti-graft versus host disease (GVHD) agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• CYP-450/Transport Proteins: Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4/5 enzyme are ineligible. Moderate inhibitors and inducers of CYP3A4/5 are permitted but caution should be exercised, and patients monitored closely for possible drug interactions. Strong inhibitors or inducers CYP3A4 should be stopped at least 2 weeks before the first dose of AZD1390 (3 weeks for St John's Wort). As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Enzyme-Inducing Anticonvulsants: Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. This includes patients with rapidly declining neurological status
• Patients must have the ability to swallow whole tablets (AZD1390 may not be administered via NG/G-tubes). Patients with medical conditions that affect drug absorption, such as short gut syndrome are not eligible
• Patients with known macular degeneration, uncontrolled glaucoma, or cataracts are not eligible
• Patients with primary spinal cord high grade gliomas are not eligible
• Patients with metastatic disease are not eligible; Metastatic disease is defined as distant intracranial or spinal metastasis including leptomeningeal disease, or tumor cells within the CSF. MRI of the spine with and without contrast must be performed if metastatic disease is suspected by the treating physician
• Patients with gliomatosis type growth pattern (or diffuse spread) with involvement of at least 3 lobes of the brain are not eligible with the exception of H3 K27M-mutant bithalamic tumors
• Patients with infant-type hemispheric high-grade gliomas are excluded

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (20)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

UMC Cancer Center / UMC Health System

Lubbock, Texas, 79415, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Astrocytoma

Interventions

AZD1390; Specimen Handling; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Therapeutics; Physical Phenomena

Study Officials

• Erin K Barr

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: March 26, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-03

Locations

US (20)