G-CSF After Chemo-radiation in Patients With Glioblastoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMassachusetts General Hospital
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must have confirmed newly diagnosed glioblastoma multiforme (GBM), World Health Organization (WHO) grade 4, IDH wildtype, either by histological or molecular criteria.
Molecular analysis needs to confirm a positive MGMT promoter methylation status using standard institutional testing methods.
Treatment needs to involve a planned 6-week course of standard of care radiation therapy with concurrent and adjuvant 6 monthly chemotherapy with temozolomide. Patients scheduled to receive an abbreviated radiation course (e.g., 3 weeks in elderly patients) are eligible.
Age ≥18 years. GBM is considered a biologically distinct disease in children. Children are excluded from this study but will be eligible for future pediatric clinical trials.
Disqualifiers
Participants who are receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to G-CSF (Filgrastim associated allergic reactions).
Participants with uncontrolled intercurrent illness that could influence leukocyte counts, such as severe infection requiring intravenous antibiotics, or known HIV (human immunodeficiency virus), since HIV/AIDS is an immunocompromising disease affecting lymphocyte counts (one of the correlative biomarkers in this study)
Pregnant women are excluded from this study because of the use of cytotoxic chemotherapy (temozolomide) and radiation, given as part of standard of care in this trial, is of teratogenic potential or has abortifacient effects. Because there is a risk for adverse events in nursing infants secondary to treatment of the mother with cytotoxic chemotherapy, breastfeeding should be discontinued if the mother is treated with cytotoxic chemotherapy.
Trial design
Design model
Parallel
Treatments tested in this trial
Granulocyte Colony Stimulating Factor (G-CSF)
DrugSubcutaneously injected study drug; standard target dose of 5-7 µg/kg/d.
Radiation Therapy + Temozolomide
RadiationStandard 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Standard Chemoradiation combined with G-CSFExperimental treatment 2 interventions
Group B: Standard ChemoradiationOther 1 intervention
Trial outcomes
Primary outcomes
1
Incidence 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.2
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).Secondary outcomes
1
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).2
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).3
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).4
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.Sponsors and contacts
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Source ClinicalTrials.gov