Using glutamate inhibitors to treat glioblastoma
A Phase Ib/II Randomized, Open Label Drug Repurposing Trial of Glutamate Signaling Inhibitors in Combination With Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma
This study is testing if adding certain medications that block glutamate can help improve treatment outcomes for people with newly diagnosed glioblastoma when used with standard chemotherapy and radiation.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 120 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Zurich Academic / other |
| Drugs / interventions | methotrexate |
| Locations | 1 site (Zurich, Canton of Zurich) |
| Trial ID | NCT05664464 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effectiveness of adding anti-glutamatergic drugs—gabapentin, sulfasalazine, and memantine—to standard chemoradiotherapy with temozolomide in patients with newly diagnosed glioblastoma. The study is designed as a 1:1 randomized, multi-center, open-label phase Ib/II trial. The rationale behind this approach is based on the role of glutamate in glioblastoma progression and the potential of these drugs to inhibit glutamate synthesis and signaling, which may improve patient outcomes. Participants will receive standard treatment alongside these additional medications to assess their combined efficacy.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 with newly diagnosed supratentorial glioblastoma eligible for standard chemoradiotherapy.
Not a fit: Patients scheduled for hypofractionated radiotherapy or those who are pregnant or breastfeeding may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve survival rates and quality of life for patients with glioblastoma.
How similar studies have performed: While there is limited commercial interest, the rationale for this combined anti-glutamatergic approach is based on existing knowledge, though it remains largely untested in this specific context.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria * Diagnosis: Newly diagnosed supratentorial glioblastoma according to the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors * Signed informed consent * Age \>18 years * Eligible for standard chemoradiotherapy with temozolomide (TMZ/RT-\>TMZ, hypofractionated RT regimen not allowed) * KPS 70 or more * Ability to judge per local investigator estimate (at least oriented to time, place and situation) * Paraffin-embedded tissue for central pathology review * Adequate heamatological, liver and renal function Exclusion criteria * Scheduled for hypofractionated radiotherapy * Women who are pregnant or breast feeding, * Intention to become pregnant during the course of the study or intention to father a child, * Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential. * Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease), * Known or suspected non-compliance, drug or alcohol abuse, * Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant, * Participation in another study with investigational drug within the 30 days preceding and during the present study, * Previous enrolment into the current study, * Being an investigator, his/her family members, employees and other dependent persons, * Any prior radiotherapy of the brain or radiotherapy with potential overlap of the irradiation fields, * Active malignancy that may interfere with the study treatment, * Abnormal ECG with QTc \>450 ms, * Contraindication for Gadolinium-enhanced MRI, * Previous intolerance reactions to one of the study drugs, * Intolerance reactions to sulfonamides or salicylates, * Acute intermittend porphyria, * Known glucose-6-phosphate dehydrogenase deficiency, * Concomitant therapy with digoxin, cyclosporin, methotrexate, * History of exfoliative dermatitis, Stevens-Johnson-Syndrome, toxic epidermal necrolysis, DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome or renal tubular acidosis.
Where this trial is running
Zurich, Canton of Zurich
- University Hospital Zurich — Zurich, Canton of Zurich, Switzerland (Recruiting)
Study contacts
- Principal investigator: Hans-Georg Wirsching, MD — University Hospital and University of Zurich
- Study coordinator: Hans-Georg Wirsching, MD
- Email: hans-georg.wirsching@usz.ch
- Phone: +41432532928
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.