Glioma
Conditions
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.
Interventions
DRUGLevetiracetam
Antiepileptic drug levetiracetam
DRUGValproic Acid
Antiepileptic drug valproic acid
Sponsors
Leiden University Medical Center
Medical Center Haaglanden
Erasmus Medical Center
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing seizure freedom at 6 months | 6 months | The percentage of patients with ongoing seizure freedom at 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Cumulative incidence of treatment failure for any reason | 36 months | Cumulative incidence function of time to treatment failure for any reason of ASM treatment using competing risk models with death as a competing event. |
| Cumulative incidence of treatment failure for specific reasons | 36 months | Cumulative incidence function of time to treatment failure for specific reasons of ASM treatment using competing risk models with death and non-applicable reasons of failure as competing events. Reasons of failure: uncontrolled seizures, adverse effects, other reasons of treatment failure, and death |
| Cumulative incidence of a first recurrent seizure | 36 months | Cumulative incidence function of time to occurrence of a first recurrent seizure after ASM initiation using competing risk models with death as a competing event. |
| 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 | Severity of adverse effects of the treatment, defined as severity (grade 1-5) of intolerable adverse effects leading to ASM discontinuation according to the Common Terminology Criteria for Adverse- Events (CTCAE) version 5.0 |
| 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 |
| 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 using MOS-CFS scores |
| 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 using HADS scale scores |
| 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) |
| 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 |
Countries
Netherlands
Contacts
CONTACTJohan AF Koekkoek, MD, PhD
CONTACTMonique Baas
Outcome results
None listed