G-CSF after chemo-radiation for MGMT-methylated glioblastoma

A Phase 2 Randomized Open-Label Pilot Study of Granulocyte Colony Stimulating Factor (G-CSF) to Preserve Brain Structure and Function Following Standard Chemoradiation in Patients With Newly Diagnosed MGMT-Methylated Glioblastoma

This test checks whether giving G-CSF after standard chemo-radiation helps protect brain structure and thinking in adults with newly diagnosed MGMT-methylated glioblastoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06649851 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized phase II trial that enrolls adults with newly diagnosed, MGMT-promoter–methylated, IDH-wildtype glioblastoma who will receive standard radiation with concurrent and adjuvant temozolomide. Participants are randomized 1:1 (stratified by age) to receive either standard chemo‑radiation alone or standard chemo‑radiation followed by G‑CSF administered after completion of chemo‑radiation and during adjuvant temozolomide. The study will measure effects on brain structure, cognitive function, overall brain health, and will monitor safety and tolerability of G‑CSF. Total participation can last up to 24 months including treatment and follow-up visits.

Who should consider this trial

Good fit: Adults (≥18 years) with newly diagnosed, histologic or molecular WHO grade 4 IDH‑wildtype glioblastoma and confirmed MGMT promoter methylation who are planned for standard radiation with concurrent and adjuvant temozolomide and have KPS >60 are eligible.

Not a fit: Patients with unmethylated MGMT, recurrent disease, prior cranial irradiation, active dementia or neurodegenerative disease, children, or those unable to receive standard chemo‑radiation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, G‑CSF could reduce treatment-related brain injury and help preserve cognitive function and quality of life for patients.

How similar studies have performed: G‑CSF is well established to prevent chemotherapy-induced neutropenia, but using G‑CSF to protect brain structure and cognition after brain cancer treatment is a novel application with limited clinical data to date.

Eligibility criteria

Inclusion Criteria:

* 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
  * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2.

For patients with Gilbert's syndrome, total bilirubin can be ≤ 3xULN.

* For participants with evidence of chronic hepatitis B virus (HBV) infection by history, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (use of granulocyte colony stimulating factor (G-CSF)) are eligible for this trial.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* 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 must be able to undergo repeated neurocognitive testing in English (or Spanish). As cognitive outcome is one of the main secondary endpoints of this study, the lack of normative and comparison data for non-English or non-Spanish-speaking patients would confound this outcome in our small sample size (see Statistical Analysis Plan for more details). Presence of significant aphasia or any other language impairment at time of diagnosis with GBM is considered an exclusion criterion. Any concerns or questions about a subject's ability to participate in neurocognitive testing can be directed to the study investigators for further discussion and clarification.
* 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.

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Jorg Dietrich, MD, PhD — Massachusetts General Hospital
• Study coordinator: Jorg Dietrich, MD, PhD

Conditions MGMT-Methylated Glioblastoma; Glioblastoma; Newly Diagnosed Glioblastoma Multiforme; MGMT-methylated glioblastoma multiforme; Newly diagnosed MGMT-methylated glioblastoma multiforme; Glioblastoma Multiforme