Enhanced Local Intensified Radiation Therapy in Elderly Glioblastoma: A Phase 2 Hybrid Randomized Trial (ELITE-GBM)

Enhanced Local Intensified Radiation Therapy in Elderly Glioblastoma (ELITE-GBM): A Phase 2 Hybrid Randomized Trial Leveraging External Data

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

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma (GBM)
• Intervention / Treatment: Radiation: Dose-escalated radiation therapy; Radiation: Standard hypofractionated radiation

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rifaquat Rahman, MD; Phone Number: 617-732-6682; Email: rrahman@bwh.harvard.edu
• Study Contact Backup: Name: Anurag Saraf, MD; Phone Number: 781-624-4700; Email: anurag_saraf@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Rifaquat Rahman, MD; Phone Number: 6177325500; Email: rrahman@bwh.harvard.edu
    • Milford, Massachusetts, United States, 01757
      • Recruiting
      • Dana-Farber Brigham Cancer Center, Milford Hospital
      • Contact: Monica Krishnan, MD; Phone Number: 5084883800; Email: mkrishnan@bwh.harvard.edu
    • South Weymouth, Massachusetts, United States, 02190
      • Recruiting
      • Dana-Farber Brigham Cancer Center, South Shore Hospital
      • Contact: Anurag Saraf, MD; Phone Number: 7816244710; Email: anurag_saraf@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalated hypofractionated radiation over 3 weeks	Radiation: Dose-escalated radiation therapy; Dose-escalated radiation therapy involves higher doses of radiation therapy each day of treatment over the three week course of radiation therapy
Active Comparator: Standard hypofractionated radiation over 3 weeks	Radiation: Standard hypofractionated radiation; Standard hypofractionated radiation therapy over 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	through study completion, an average of 1 year	Overall survival from time of enrollment through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival		Time of enrollment to time of progressionfrom time of enrollment through study completion, an average of 6 months
Treatment-related toxicity	Per CTCAE 5.0	Time of enrollment to end of treatment (upto 6 months after completion of radiation therapy)
Health-related quality of life	This will be measured by EORTC QLQ-C30 and QLQ-BN20 tools. Evaluation for changes in health-related quality of life by these instruments upto 6 months after radiation therapy.	From time of enrollment upto 6 months later
Mood symptoms	Measured by the Patient Health Questionnaire (PHQ-4). Evaluation of changes to PHQ-4 scores over time upto 6 months after radiation treatment.	From time of enrollment upto 6 months later
Practical Geriatric Assessment		From time of enrollment upto 6 months later
Performance status	Measured by Karnofsky Performance Status. Evaluation of changes of performance status over time upto 6 months after radiation treatment.	From time of enrollment upto 6 months later

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 14, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: glioblastoma; hypofractionation; elderly glioblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 24-637

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will plan to share IPD pending securing funding to facilitate data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No