This research study involves the study of granulocyte colony stimulating factor (G-CSF) in patients with MGMT-methylated glioblastoma multiforme (GBM) that are undergoing standard chemoradiation. The study aims to evaluate G-CSF's effects on brain health and cognitive function. The name of the study drugs involved in this study are: * G-CSF (also called Filgrastim) * Temozolomide (TMZ), a standard of care chemotherapy drug
This is an open-label, randomized, phase II clinical study of using G-CSF in patients with newly diagnosed, MGMT-methylated, GBM treated with standard of care radiation with concurrent and adjuvant chemotherapy with temozolomide. The investigators are testing whether G-CSF can reduce the negative side effects from radiation and chemotherapy on brain health. The investigators are specifically testing the effects of G-CSF on brain structure, cognitive function, and general brain health, and the safety and tolerability of G-CSF. Participants will be randomized, stratified by age, in a 1:1 fashion to receive either standard of care chemo-radiation (chemo-RT) in combination with G-CSF, or standard of care chemo-RT without G-CSF. Treatment with G-CSF will be initiated after chemo-RT and be completed after 6 cycles of adjuvant chemotherapy with Temozolomide. This study involves screening for eligibility, standard of care radiation therapy and chemotherapy, study treatment and study visits, and follow-up visits. Participants will be in the study for up to 24 months, including 6 weeks of standard of care chemo-RT, up to 7 months of G-CSF treatment (depending on the number of additional chemotherapy cycles given as a part of standard care) and up to 7 months of active follow-up visits after study treatment ends followed by 12 months of survival follow-up. Up to 60 participants will be enrolled in this study. Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates bone marrow to produce stem cells and blood cells and release them into the bloodstream. It is known to have anti-inflammatory and neuroprotective properties (slowing or halting the loss of neurons). G-CSF is also called Filgrastim, and brand names include Granix®, Neupogen®, and Zarxio®. In addition to testing the safety and tolerability of G-CSF, the researchers in this study are testing whether or not G-CSF can protect cells in the brain or enhance repair in the brain after chemoradiation and during chemotherapy. The U.S. Food and Drug Administration (FDA) has not approved G-CSF to support brain health and cognitive function. However, G-CSF has been approved for several decades and in patients with any type of cancer who develop neutropenia (low white blood cell counts) following chemotherapy, including in patients with glioblastoma, or in patients following stem cell transplantation with low white cell blood counts. The U.S. Food and Drug Administration (FDA) has approved temozolomide as a treatment option for GBM. Temozolomide is given as standard of care chemotherapy in this study. The radiation therapy used in this study is standard of care and approved by the U.S. Food and Drug Administration (FDA) as a treatment option for GBM.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Subcutaneously injected study drug; standard target dose of 5-7 µg/kg/d.
Standard of care chemoradiation is radiation therapy + Temozolomide (TMZ). Chemoradiation (chemo-RT) includes an initial 6-week cycle, followed by a 4-week break, and up to 6 additional cycles of TMZ.
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGIncidence of adverse events (AEs)
Adverse events (AEs) will be assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will be listed and tabulated by type and study arm. AEs will also be categorized as study-related or not. The rate of AEs in all participants, both within study arms and overall, will be calculated and reported with exact 95% confidence intervals. All subjects who have completed at least 3 weeks of cranial radiation therapy will be include in the safety analyses.
Time frame: From Day 0 (start of chemoradiotherapy (chemo-RT)) to end of treatment (EoT) +30 days, up to 35 weeks total.
Change in Brain Volume from Baseline
The degree of ventricular volume expansion (measured in % change from baseline) will be assessed by Magnetic Resonance Imaging (MRI), and serving as a surrogate marker for global brain volume loss and compared to a randomized control group. The contra-lesional lateral ventricle will be segmented in 3D Slicer or similar program to calculate the ventricular volume at each time point. Descriptive statistics with 95% CI will be provided for all endpoints and normality of data distribution will be assessed. If needed, Wilcoxon Rank-Sum test will be used to compare changes in ventricular volume expansion from baseline to endpoints between the groups and the Sign-rank tests will be used to evaluate within group changes between time points (two-sample or paired T-test will be used respectively if the data distribution warrants a parametric approach).
Time frame: Screening (completed in Day -28 through Day 0) through up to 7 months after end of treatment (up to 62 weeks total).
Change in Neurocognitive Function (NCF)
Measured using a battery of standardized psychometric instruments (HVLT; COWA; TMT A; TMT B; Coding; Wechsler Adult Intelligence Scale; HVLT Delayed Recall; HVLT Recognition) at screening, 1 month after end of chemo-RT, and 6- and 12- months after EoT. 7 cognitive scores will be calculated, 3 for the HVLT and one for each of the other tests. Raw scores for each cognitive metric will be converted to Z-scores using published normative data. A composite score will also be calculated by averaging the 7 test scores for each subject at each time point. Changes from baseline are calculated by subtracting baseline from each of the follow-up scores. Percent change will be calculated as change from baseline divided by baseline. The difference between the pre-treatment baseline and follow-up NCF scores will be determined by the reliable change index (RCI).
Time frame: Screening (completed in Day -28 through Day 0) through up to 7 months after end of treatment (up to 62 weeks total).
Change in Quality of Life (QOL)
Participant-reported QOL will be measured using the validated Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br). Scores (ranging from 0 to 4) for each domain as well as a total QOL score are calculated. FACT-Br subscales will be combined and analyzed for change in each of the FACT-Br indices, as well as the total score and subjective cognitive function scores. Analysis approach will include regression modeling. Changes from baseline will be calculated by subtracting baseline from each of the follow-up scores. Percent change will be calculated as change from baseline divided by baseline.
Time frame: Screening (completed in Day -28 through Day 0) through up to 7 months after end of treatment (up to 62 weeks total).
Change in Mood using Hospital Anxiety and Depression Scale (HADS)
Participant-reported mood will be measured using the Hospital Anxiety and Depression Scale (HADS) . Scores on 2 subscales (ranging from 0 to 21) for each domain are calculated. Scores will be analyzed for change. Analysis approach will include regression modeling. Analysis approach will include regression modeling. Changes from baseline will be calculated by subtracting baseline from each of the follow-up scores. Percent change will be calculated as change from baseline divided by baseline.
Time frame: Screening (completed in Day -28 through Day 0) through up to 7 months after end of treatment (up to 62 weeks total).
Overall Survival (OS)
Defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Data will be listed, tabulated, and presented descriptively using Kaplan Meier plots.
Time frame: Screening (completed in Day -28 through Day 0) through 24 months after enrollment.
Progression-Free Survival (PFS)
Defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Calculated using the Kaplan Meier method.
Time frame: Screening (completed in Day -28 through Day 0) through 24 months after enrollment.
Time to Progression (TTP)
Defined as the time from randomization (or registration) to progression, or censored at date of last disease evaluation for those without progression reported. Calculated using the Kaplan Meier method.
Time frame: Screening (completed in Day -28 through Day 0) through 24 months after enrollment.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.