Glioblastoma (GBM)
Conditions
Keywords
glioblastoma, elderly glioblastoma, hypofractionation
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
Interventions
RADIATIONDose-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
RADIATIONStandard hypofractionated radiation
Standard hypofractionated radiation therapy over 3 weeks
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Overall survival from time of enrollment through study completion, an average of 1 year | through study completion, an average of 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related toxicity | Time of enrollment to end of treatment (upto 6 months after completion of radiation therapy) | Per CTCAE 5.0 |
| Health-related quality of life | From time of enrollment upto 6 months later | 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. |
| Progression-free survival | Time of enrollment to time of progressionfrom time of enrollment through study completion, an average of 6 months | — |
| Practical Geriatric Assessment | From time of enrollment upto 6 months later | — |
| Performance status | From time of enrollment upto 6 months later | Measured by Karnofsky Performance Status. Evaluation of changes of performance status over time upto 6 months after radiation treatment. |
| Mood symptoms | From time of enrollment upto 6 months later | Measured by the Patient Health Questionnaire (PHQ-4). Evaluation of changes to PHQ-4 scores over time upto 6 months after radiation treatment. |
Countries
United States
Contacts
Primary ContactRifaquat Rahman, MD
Backup ContactAnurag Saraf, MD
Outcome results
None listed