Seizure Treatment in Glioma
- Registration Number
- NCT03048084
- Lead Sponsor
- Leiden University Medical Center
- Brief Summary
Currently, treatment with a specific anti-epileptic drug mainly depends on the physicians' preference, as there are no studies supporting the use of one specific anticonvulsant in glioma patients. The overall aim of this randomized controlled trial is to directly compare the effectiveness of treatment with levetiracetam or valproic acid in glioma patients with a first seizure.
- Detailed Description
Currently, treatment of glioma patients with a specific anti-epileptic drug (AED) mainly depends on the physicians' preference, as there is no robust evidence from randomized controlled trials supporting the use of one specific anticonvulsant above the other in glioma patients.
Levetiracetam and valproic acid are the most commonly used AEDs in glioma patients. Both drugs are used for the treatment of seizures, have similar toxicity profiles and are non-enzyme inducing AEDs, therefore not interfering with chemotherapeutic drugs. However, it is not known whether one drug is more effective than the other in reducing seizures.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- Histologically proven or suspected diffuse astrocytoma (Isocytrate Dehydrogenase-1 (IDH-1) wildtype or IDH-1 mutated), diffuse oligodendroglioma (IDH-1 mutated and 1p/19q co-deleted), anaplastic astrocytoma (IDH-1 wildtype or IDH-1 mutated), anaplastic oligodendroglioma (IDH-1 mutated and 1p/19q co-deleted), glioblastoma (IDH-1 wild-type or IDH-1 mutated), or diffuse astrocytoma not otherwise specified (NOS), anaplastic astrocytoma NOS, oligodendroglioma NOS, oligoastrocytoma NOS, anaplastic oligoastrocytoma NOS, anaplastic oligodendroglioma NOS or glioblastoma NOS.
- Adult patients: ≥18 years of age
- First epileptic seizure, no longer than 2 weeks ago
- Monotherapy with antiepileptic drugs is considered most appropriate at the time of randomization
- Willing to provide written informed consent
- Previously treated with antiepileptic drugs, except emergency treatment in the past 2 weeks
- History of non-brain tumor related epilepsy
- Pregnancy
- Presence of contra-indications for use of levetiracetam or valproic acid
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Levetiracetam Levetiracetam Patients in this treatment arm will receive levetiracetam monotherapy. The dosage depends on the specific treatment step, as indicated in the protocol. In step 1, patients will receive 2x500 mg/d levetiracetam in the form of tablets. In step 2, dosage is increased to 1x250 plus 1x500 mg/d and in step 3 to 2x1000 mg/d levetiracetam. In step 4, levetiracetam is increased to 2x1500mg/d. In the fifth treatment step, patients will receive 2x1500 mg/d levetiracetam, and another AED will be added. The type and dosage of this add-on AED is according to the physician's preference, but in line with current clinical practice in the Netherlands. Valproic acid Valproic Acid Patients in this treatment arm will receive valproic acid monotherapy. The dosage depends on the specific treatment step, as indicated in the protocol. In step 1, patients will receive 2x500 mg/d valproic acid in the form of tablets. In step 2, dosage is increased to 1x250 plus 1x500 mg/d and in step 3 to 2x1000 mg/d valproic acid. In step 4, valproic acid dosage is increased to a maximum of 2x1250mg/d. In the fifth treatment step, patients will receive 2x1250mg valproic acid, and another AED will be added. The type and dosage of this add-on AED is according to the physician's preference, but in line with current clinical practice in the Netherlands.
- Primary Outcome Measures
Name Time Method Ongoing seizure freedom at 6 months 6 months The percentage of patients with ongoing seizure freedom at 6 months
- Secondary Outcome Measures
Name Time Method Health-related quality of life 0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Health-related quality of life
Cognitive complaints 0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Cognitive complaints
Mood 0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Anxiety and depression
Performance Status 0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Karnofsky Performance Status Score
Epilepsy burden 0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Epilepsy burden
Treatment response 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Treatment response (e.g., maximum dosage of AED, use of add-on AED)
Progression-free survival 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Progression-free survival
Overall survival 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Overall survival
Time to 6 months seizure freedom 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Time to 6 months seizure freedom
Seizure outcome at 12 months 12 months Seizure outcome at 12 months
Adverse effects of the treatment 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively Adverse effects of the treatment
Hospitalisation rate 0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively hospitalization rate due to treatment failure
Trial Locations
- Locations (5)
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Haaglanden Medical Center
🇳🇱The Hague, Netherlands