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

NCT06835803 | Recruiting Phase 2

• 1 other identifier: 24-637
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

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. 1.Standard hypofractionated radiation over 3 weeks
2. 2.Dose-escalated hypofractionated radiation over 3 weeks

Conditions

Glioblastoma (GBM)

Keywords

glioblastoma; elderly glioblastoma; hypofractionation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression-free survival

  Time of enrollment to time of progressionfrom time of enrollment through study completion, an average of 6 months

• Treatment-related toxicity

  Time of enrollment to end of treatment (upto 6 months after completion of radiation therapy)

• Health-related quality of life

  From time of enrollment upto 6 months later

• Mood symptoms

  From time of enrollment upto 6 months later

• Practical Geriatric Assessment

  From time of enrollment upto 6 months later

Study Arms (2)

Dose-escalated hypofractionated radiation over 3 weeks

EXPERIMENTAL

Radiation: Dose-escalated radiation therapy

Standard hypofractionated radiation over 3 weeks

ACTIVE COMPARATOR

Radiation: Standard hypofractionated radiation

Interventions

Dose-escalated radiation therapy RADIATION

Dose-escalated radiation therapy involves higher doses of radiation therapy each day of treatment over the three week course of radiation therapy

Dose-escalated hypofractionated radiation over 3 weeks

Standard hypofractionated radiation RADIATION

Standard hypofractionated radiation therapy over 3 weeks

Standard hypofractionated radiation over 3 weeks

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Brigham Cancer Center, Milford Hospital

Milford, Massachusetts, 01757, United States

RECRUITING

Dana-Farber Brigham Cancer Center, South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Rifaquat Rahman, MD

CONTACT

617-732-6682; rrahman@bwh.harvard.edu

Anurag Saraf, MD

CONTACT

781-624-4700; anurag_saraf@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: February 19, 2025
• Study Start: April 14, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

US (3)