XRD-0394 with radiation therapy for high-grade glioma

A Phase 0/I Study to Assess the Safety and Tolerability of XRD-0394 in Combination With Radiation Therapy in Patients With High Grade Gliomas

This trial tests whether adding the experimental drug XRD-0394 to radiation (and for some patients to temozolomide) is safe and helpful for adults with newly diagnosed or recurrent high-grade glioma.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NYU Langone Health (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (New York, New York)
• Trial ID: NCT06829173 on ClinicalTrials.gov

What this trial studies

This open-label, early-phase 1 dose-finding study gives escalating doses of XRD-0394 alongside standard radiation therapy in adults with newly diagnosed or recurrent high-grade gliomas. Newly diagnosed patients receive temozolomide based on MGMT status, while recurrent patients receive radiation with XRD-0394 as indicated; surgical resection may be part of standard care. Enrollment requires biopsy-confirmed high-grade glioma for some cohorts, ECOG performance status ≤2, and adequate liver and kidney function. The trial aims to identify a recommended dose, characterize side effects, and collect early signals of anti-tumor activity and safety.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed or recurrent biopsy-confirmed high-grade glioma who have ECOG ≤2, adequate liver and kidney function, and can provide informed consent and attend visits at the study site are the best candidates.

Not a fit: Patients with poor performance status (ECOG >2), significant hepatic or renal dysfunction, non–high-grade tumor histology, or inability to travel to the study center are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, combining XRD-0394 with radiation could improve local tumor control and potentially delay progression or extend survival for people with high-grade glioma.

How similar studies have performed: Other early-phase efforts combining experimental systemic agents with radiation in high-grade glioma have produced mixed results—occasionally showing local control benefits in small groups but remaining largely unproven—so this approach for XRD-0394 is novel and exploratory.

Eligibility criteria

Inclusion Criteria:

* Willing and able to provide written informed consent.
* ≥18 years of age.
* For Cohorts A and B, radiographic diagnosis of high-grade glioma that is then confirmed with biopsy. Patients with established histologic diagnosis of high-grade glioma is able to enroll on the study without repeating biopsy.
* For Cohort C, histologic diagnosis of high-grade glioma is required to enroll on the study.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* Subjects must have adequate liver and kidney function, defined as: Liver transaminase levels ≤2.5 × the upper limit of normal (ULN); total bilirubin ≤1.5 × ULN, except in subjects with Gilbert's Disease in whom total bilirubin ≤5 × ULN is allowed; OR Creatinine clearance ≥60 mL/min measured from a 24-hour urine collection or calculated based on the Cockcroft-Gault formula.
* Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy. Female subjects of childbearing potential who are undergoing RT or who are partners to male subjects in the study should avoid sexual activity or use a highly effective method of birth control during sexual intercourse. Acceptable, highly effective methods of birth control include intrauterine device (IUD)/intrauterine hormone releasing system (IUS), bilateral tube occlusion, vasectomized partner, combined (estrogen and progesterone containing) or progesterone-only hormonal contraceptives (oral, intravaginal, transdermal, injectable).
* Subjects receiving anti-glioma therapy are eligible if treatment can be held 14 days before the first XRD-0394 dose and resume a minimum of 5 days after completion of XRD-0394 (Cohort C only).
* Patient with recurrent tumor amendable to reirradiation and is at least 3 months from end of prior brain radiation therapy (Cohort C only)
* Subjects taking glucocorticoids before and during protocol treatment period will be included per the discretion of the investigator. Intake should be minimized before and during treatment.

Exclusion Criteria:

* Prior radiotherapy to the same region or prior anti-glioma systemic therapy in patients with newly diagnosed HGG (Cohorts A and B, not applicable for Cohort C)
* Subjects with bone marrow impairment as evidenced by hemoglobin \<8.0 g/dL, neutrophil count \<1.5 × 109/L, or platelets \<100 × 109/L.
* History of difficulty swallowing, malabsorption or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption of XRD-0394, use of percutaneous endoscopic gastrostomy (PEG) tubes.
* Significant cardiac conduction abnormalities, including a history of long corrected QT (QTc) interval syndrome (\>450 msec per Fridericia's formula) and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification \>2 at screening.
* Participation in another investigational study of an unapproved drug or device or treatment with another ATM, deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK), or ataxia-telangiectasia and Rad3-related (ATR) inhibitor within 28 days of the first dose of XRD-0394.
* Subjects who are pregnant or breast-feeding.
* Subjects with a QTc interval \>450 msec (calculated using Fridericia's QT correction formula) at screening.
* Contraindication to temozolomide (Cohort A only)
* Severe headache, rapidly progressive neurologic decline, objective neurologic manifestations of uncal herniation, depressed level of consciousness
* Subjects receiving treatment with any drug that is a strong inhibitor or inducer of CYP3A4 enzyme activity or an inhibitor of BCRP within a minimum of 5 half- lives or 14 days prior to screening or during study participation.

Where this trial is running

New York, New York

• NYU Langone Health — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jonathan Yang, MD, PhD — NYU Langone Health
• Study coordinator: Jonathan Yang, MD, PhD

Conditions High-Grade Glioma