enhanced local intensified radiation therapy in elderly glioblastoma: a phase 2 hybrid randomized trial

Conditions: Glioblastoma (GBM)

Summary: glioblastoma (gbm) is an aggressive malignancy of the central nervous system. older adults with gbm have a unique constellation of medical, psychosocial, and supportive care needs. to address these challenges, prior work has evaluated the feasibility of hypofractionation, a treatment approach delivering fewer, larger radiation dosages over a shorter time period. common hypofractionated regimens deliver a lower biologically equivalent radiation dose than the conventional regimens used for younger adults. whether dose escalated hypofractionation can further improve outcomes in older adults remains unclear. this will be a hybrid randomized control trial comparing the efficacy and safety of dose-escalated and standard hypofractionated radiotherapy among older adults with newly-diagnosed glioblastoma compared to standard three-week course. this research study involves the administration of radiation therapy. radiation will either be delivered at the standard daily dose or at an increased daily dose over a three weeks course of radiation treatment. research study procedures will include a screening evaluation to assess eligibility, as well as clinical visits for radiation delivery and to assess symptoms during treatment and at scheduled follow-up times. participants will be randomly assigned to one of the two arms of the trial: 1. standard hypofractionated radiation over 3 weeks 2. dose-escalated hypofractionated radiation over 3 weeks


Eligibility criteria:
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.

Keywords: glioblastoma elderly glioblastoma hypofractionation