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 is an open-label, dose-finding study of XRD-0394 in subjects with newly diagnosed and recurrent high grade gliomas receiving radiation therapy, with and without concurrent temozolomide based on O6-Methylguanine-DNA methyltransferase (MGMT) status for patients with newly diagnosed high grade gliomas.
• 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.