Clinical trial NCT06835803: Enhanced Local Intensified Radiation Therapy in Elderly Glioblastoma: a Phase 2 Hybrid Randomized Trial
Official title: Enhanced Local Intensified Radiation Therapy in Elderly Glioblastoma (ELITE-GBM): a Phase 2 Hybrid Randomized Trial Leveraging External Data
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma (GBM)
Keywords: glioblastoma
elderly glioblastoma
hypofractionation
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 56
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will use a hybrid design that also leverages an external control dataset in order to adjust the randomization ratio in favor of the experimental arm.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Overall survival
timeFrame: Overall survival from time of enrollment through study completion, an average of 1 year
Secondary outcomes:
measure: Progression-free survival
timeFrame: Time of enrollment to time of progressionfrom time of enrollment through study completion, an average of 6 months
measure: Treatment-related toxicity
timeFrame: Time of enrollment to end of treatment (upto 6 months after completion of radiation therapy)
measure: Health-related quality of life
timeFrame: From time of enrollment upto 6 months later
measure: Mood symptoms
timeFrame: From time of enrollment upto 6 months later
measure: Practical Geriatric Assessment
timeFrame: From time of enrollment upto 6 months later
measure: Performance status
timeFrame: From time of enrollment upto 6 months later
Other outcomes:
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