Hypoxia-targeted Radiotherapy Boost for GBM

HYPO2-BOOST GBM Trial: Hypoxia-targeted Radiotherapy Boost for GBM

The purpose of this study is to evaluate the use of dynamic contrast-enhanced MRI (DSC-MRI) to identify and target hypoxic tumor regions in glioblastoma (GBM). The study is divided into two phases: Phase 1 will focus on biologic validation in newly diagnosed GBM patients, while Phase 2 will assess the clinical implementation of DSC-MRI-guided radiotherapy in recurrent or postoperative GBM patients. The primary endpoints are the validation of DSC-MRI in identifying hypoxic regions and assessing the safety and efficacy of radiation therapy based on these findings.

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. ≥18 years of age.
3. All suspected GBM patients including newly diagnosed and recurrent GBM who are undergoing resection (Phase 1). Or all suspected newly diagnosed or recurrent GBM being treated with radiation where there is still visible tumor) (Phase 2)
4. Participants with a history of prior malignancies and previous LITT are permitted to enroll.
5. KPS > 50.
6. Subjects must have adequate liver and kidney function, defined as:
7. 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.
8. Creatinine clearance ≥60 mL/min measured from a 24-hour urine collection or calculated based on the Cockcroft-Gault formula OR serum creatinine ≤ULN.
9. 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).
10. Patient with recurrent tumor amendable to reirradiation and is at least 3 months from end of prior brain radiation therapy

Exclusion Criteria:

Subjects must not meet any of the following criteria to be eligible for study participation:

1. Subjects with bone marrow impairment as evidenced by hemoglobin <8.0 g/dL, neutrophil count <1.5 × 109/L, or platelets <100 × 109/L.
2. 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.
3. Subjects who are pregnant or breast-feeding.
4. Contraindication to temozolomide
5. Severe headache, rapidly progressive neurologic decline, objective neurologic manifestations of uncal herniation, depressed level of consciousness