G-CSF After Chemo-radiation in Patients With Glioblastoma

NCT06649851 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-580
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

MGMT-Methylated Glioblastoma; Glioblastoma (GBM); Newly Diagnosed Glioblastoma Multiforme

Keywords

MGMT-methylated glioblastoma multiforme (GBM); Newly diagnosed MGMT-methylated glioblastoma multiforme (GBM); Glioblastoma; Glioblastoma Multiforme (GBM)

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Screening (completed in Day -28 through Day 0) through up to 7 months after end of treatment (up to 62 weeks total).

Secondary Outcomes (6)

• Change in Neurocognitive Function (NCF)

  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)

  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)

  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)

  Screening (completed in Day -28 through Day 0) through 24 months after enrollment.

• Progression-Free Survival (PFS)

  Screening (completed in Day -28 through Day 0) through 24 months after enrollment.

Study Arms (2)

Standard Chemoradiation combined with G-CSF

EXPERIMENTAL

Per standard of care, participants undergo a 6-week chemoradiation (chemo-RT) cycle followed by a 4-week break. During this 4-week break after chemo-RT, participants receive granulocyte colony stimulating factor (G-CSF) once per day for 5 days (Days 7-11). After the 4-week break, as a part of standard care, participants may then receive up to 6 additional 4-week cycles of chemotherapy (temozolomide (TMZ)). During these additional TMZ cycles, participants will receive G-CSF once per day for 3 consecutive days (Days 14-16). G-CSF is injected under the skin (subcutaneously injected) by a study staff member, or self-administered (or a caregiver) can be trained by a study staff member to administer it at home. The chemo-RT (radiation therapy and chemotherapy (TMZ)) are standard of care in this study.

Drug: Granulocyte Colony Stimulating Factor (G-CSF); Radiation: Radiation Therapy + Temozolomide

Standard Chemoradiation

OTHER

Participants receive standard of care chemoradiation (chemo-RT) which includes an initial 6-week chemo-RT cycle followed by a 4-week break, and up to 6 additional 4-week chemotherapy (temozolomide (TMZ)) cycles.

Radiation: Radiation Therapy + Temozolomide

Interventions

Radiation Therapy + Temozolomide RADIATION

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.

Also known as: Chemo-RT, chemoradiation

Standard Chemoradiation; Standard Chemoradiation combined with G-CSF

Granulocyte Colony Stimulating Factor (G-CSF) DRUG

Subcutaneously injected study drug; standard target dose of 5-7 µg/kg/d.

Also known as: G-CSF, Filgrastim, Granix, Neupogen, Zarxio

Standard Chemoradiation combined with G-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Karnofsky Performance Status (KPS) \> 60, see Appendix A
• No prior cranial irradiation.
• No existing diagnosis of clinical dementia or high clinical suspicion for presence of any neurodegenerative disease (e.g., Alzheimer's Disease, Fronto-temporal Dementia (FTD), Parkinson's Disease, Motor Neuron Disease, etc.) prior to diagnosis of GBM.
• Life expectancy of greater than 6 months.
• Must be able to undergo repeated brain Magnetic resonance imaging (MRI) studies with administration of gadolinium (contrast enhanced brain MRI).
• Participants must have adequate organ and bone marrow function (as defined below) to be able to receive standard chemoradiation therapy:
• leukocytes ≥2,500/mcL
• absolute neutrophil count≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT)≤3 × institutional ULN creatinine≤ institutional ULN OR

You may not qualify if:

• 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.
• Participants with active thromboembolic event (pulmonary embolism or deep venous thrombosis) or prior thromboembolic event within 6 months prior to diagnosis of GBM may need to be excluded because of possible risks of thromboembolism with the use of G-CSF and will require further discussion with the PI prior to enrollment on a case-by-case basis.
• Participants with the following medical conditions are excluded and not eligible based on elevated risk of G-CSF associated toxicity: Sickle cell disease or sickle cell trait, congenital neutropenia, hematological malignancy (leukemia or myelodysplastic syndrome).
• Patients who are dependent on high doses of corticosteroids equivalent to 8mg of daily dexamethasone or more, or who are expected to be unable to taper steroids post-operatively to a dose of 4mg of dexamethasone or less prior to start of chemo-RT.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Radiotherapy; Temozolomide; Chemoradiotherapy

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Drug Therapy

Study Officials

• Jorg Dietrich, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorg Dietrich, MD, PhD

CONTACT

617-724-8770; jdietrich1@partners.org

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: Principal Investigator

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 21, 2024
• Study Start: April 2, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)