Print

Purpose

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

Condition

Eligibility

Eligible Ages
Over 65 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926 02115
Contact:
Rifaquat Rahman, MD
6177325500
rrahman@bwh.harvard.edu

Dana-Farber Brigham Cancer Center, Milford Hospital
Milford 4943958, Massachusetts 6254926 01757
Contact:
Monica Krishnan, MD
5084883800
mkrishnan@bwh.harvard.edu

More Details

Status
Recruiting
Sponsor
Brigham and Women's Hospital

Study Contact

Rifaquat Rahman, MD
617-732-6682
rrahman@bwh.harvard.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.