Actively Recruiting
A Phase 0/I Study to Assess the Safety and Tolerability of XRD-0394 With Radiation Therapy in Patients With High Grade Gliomas
Led by NYU Langone Health · Updated on 2026-01-02
39
Participants Needed
1
Research Sites
208 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and tolerability of XRD-0394, a drug given with radiation therapy, in people with newly diagnosed or recurrent high-grade gliomas, a type of brain tumor. This early-phase study aims to find the best dose of XRD-0394, which may be given with or without the chemotherapy drug temozolomide depending on patients' tumor MGMT gene status. The study is open-label and includes different groups based on treatment timing and tumor characteristics. Participants receive XRD-0394 orally at varying doses during radiation therapy. Newly diagnosed patients may join a pre-surgical dose escalation phase with two dose levels before surgery. After surgery, patients with MGMT-methylated or unmethylated tumors enter separate cohorts receiving different doses of XRD-0394 two or three times weekly with radiation. Patients with recurrent tumors join a different cohort with similar dose levels during radiation. Radiation doses vary by cohort, and surgical tumor removal is part of treatment for some groups. During the study, participants undergo assessments including monitoring for dose-limiting toxicities at specific time points depending on their group. Tumor tissue is analyzed for drug concentration on the day of surgery. Researchers also track progression-free and overall survival for up to three years. Participants will have regular visits for safety and effectiveness evaluations throughout the study period, which begins with screening and includes treatment and follow-up phases lasting several months to years.
CONDITIONS
Brief Title
Concurrent XRD-0394 With Radiation Therapy for High Grade Gliomas
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Willing and able to provide written informed consent.
- 18 years of age or older.
- For Cohorts A and B, radiographic diagnosis of high-grade glioma confirmed by biopsy, or established histologic diagnosis.
- For Cohort C, histologic diagnosis of high-grade glioma is required.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Adequate liver function: Liver transaminase levels ≤2.5 times the upper limit of normal; total bilirubin ≤1.5 times upper limit of normal (or ≤5 times with Gilbert's Disease).
- Adequate kidney function: Creatinine clearance ≥60 mL/min.
- Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to avoid pregnancy using highly effective contraception.
- Subjects receiving anti-glioma therapy are eligible if treatment can be paused 14 days before XRD-0394 and resumed at least 5 days after (Cohort C only).
- Patients with recurrent tumor suitable for reirradiation and at least 3 months from prior brain radiation (Cohort C only).
- Subjects taking glucocorticoids before and during treatment may be included at investigator discretion, with minimized intake.
You will not qualify if you...
- Prior radiotherapy to the same region or prior anti-glioma systemic therapy in newly diagnosed patients (Cohorts A and B).
- Bone marrow impairment: hemoglobin <8.0 g/dL, neutrophils <1.5 × 10⁹/L, or platelets <100 × 10⁹/L.
- History of swallowing difficulties, malabsorption, chronic gastrointestinal disease, or use of PEG tubes.
- Significant cardiac conduction abnormalities or impaired cardiovascular function (NYHA class >2).
- Participation in another investigational study with ATM, DNA-PK, or ATR inhibitors within 28 days before XRD-0394.
- Pregnant or breastfeeding.
- QTc interval >450 msec at screening.
- Contraindication to temozolomide (Cohort A only).
- Severe headache, rapidly worsening neurological decline, signs of uncal herniation, or reduced consciousness.
- Treatment with strong CYP3A4 or BCRP inhibitors or inducers within 5 half-lives or 14 days before screening or during the study.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 8 days until day of surgery
Participants with newly diagnosed high grade gliomas receive XRD-0394 orally on radiation therapy days before surgical tumor resection.
Daily visits during radiation therapy before surgery
Duration - 1 day
Participants undergo surgical removal of tumor tissue.
1 visit (in-person, day of surgery)
Duration - Approximately 15 weeks of radiation therapy
Participants in Cohorts A and B receive XRD-0394 orally concurrently with radiation therapy at assigned dose levels following surgery.
Weekly visits during radiation therapy for up to 32 fractions
Duration - Approximately 2 weeks of radiation therapy
Participants in Cohort C with recurrent glioma receive XRD-0394 orally concurrently with radiation therapy without surgery.
Weekly visits during radiation therapy for up to 10 fractions
Duration - Up to 3 years post enrollment
Participants are monitored for safety and progression up to 3 years after treatment.
Periodic follow-up visits
Trial Site Locations
Total: 1 location
1
NYU Langone Health
New York, New York, United States, 10016
Actively Recruiting
Research Team
J
Jonathan Yang, MD, PhD
C
Cancer Trials NYU Langone
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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