Enhanced Local Intensified Radiation Therapy in Elderly Glioblastoma: A Phase 2 Hybrid Randomized Trial

Inclusion Criteria:

* Histological confirmation of WHO grade 4 glioblastoma (IDH wild-type by immunohistochemistry or sequencing). Histopathology must be confirmed by central review.
* Newly diagnosed disease, with time elapsed from diagnostic surgery/resection \<8 weeks.
* Age ≥ 65 years old at time of glioblastoma diagnosis
* Adequate functional status as measured by a ECOG Performance Status 0, 1 or 2, at time of enrollment.
* Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 45 days prior to randomization:

Platelet count ≥ 100 x 10\^9/L (100,000 cells/mm\^3) Serum creatinine ≤ 1.5 times the upper limit of normal Total serum bilirubin ≤ 1.5 times the upper limit of normal ALT (SGPT) \< 2.5 times the upper limit of normal and/or AST (SGOT) \< 2.5 times the upper limit of normal

-Patient may have received corticosteroids, but must be on a stable or decreasing dose for at least 14 days prior to randomization.

Exclusion Criteria:

* Participants with recurrent glioma.
* Participants with evidence of spinal, leptomeningeal, or more distant disease.
* Participants with another active central nervous system malignancies requiring treatment.
* Participants with a second invasive malignancy that is A) incompletely treated or requiring ongoing treatment, or B) reasonably anticipated to be associated with a median overall survival of less than 1 year based on population-level data for the specified disease site and stage.
* Participants with any other major medical illnesses or psychiatric treatments that in the treating physician's opinion will prevent administration or completion of protocol therapy.
* Participants with inadequate mental capacity to provide informed consent
* Participants who cannot receive gadolinium
* Participants who have undergone prior head and neck or cranial radiation or radiation to any other site previously that would be reasonably anticipated to result in a significant overlap in radiation fields.
* Participants who have received systemic or radiosensitizing therapy for a prior head and neck or central nervous system malignancy or any investigational cancer drug for glioblastoma prior to randomization.
* Participants who have received or plan to receive any other form of non-surgical local or field treatment overlapping with the anticipated radiation field.
* Patients with a serious active infection (such as a wound infection requiring parenteral antibiotics) or other acute medical conditions at the time of randomization that would impair the ability of the patient to receive protocol treatment.