Glutamate Inhibitors in 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
University of Zurich
120 participants
Jan 1, 2023
INTERVENTIONAL
Conditions
Summary
The goal of this 1:1 randomized, multi-center, open-label phase Ib/II clinical trial is to explore the efficacy of the add-on of the anti-glutamatergic drugs gabapentin, sulfasalazine and memantine to standard chemoradiotherapy with temozolomide compared to chemoradiotherapy alone in patients with newly diagnosed glioblastoma.
Eligibility
Inclusion Criteria8
- 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 Criteria20
- 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.
Interventions
Weekly dose escalations over 4 weeks of daily 3 x 300 mg up to 3 x 1200 mg
Weekly dose escalations over 3 weeks of daily 3 x 500 mg up to 3 x 1500 mg
Weekly dose escalations over 4 weeks of daily 1 x 5-20 mg
Concomitant with radiotherapy at 75 mg/m2 daily followed by maintenance 150-200 mg/m2 on 5/28 days
30 x 2 Gy involved field radiotherapy with concomitant temozolomide
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05664464