GliomaPhase 4STINGNCT03048084
Seizure Treatment in Glioma
A Phase 4 study testing Levetiracetam and Valproic Acid in people with Glioma, run by Leiden University Medical Center at 5 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- Levetiracetam and Valproic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 5 sitesNetherlands
- Study dates
- 1 Feb 2018to 1 Jul 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Netherlands5 sites, 4 recruiting
- Suspended
Amsterdam UMC
Amsterdam, 1007 MB
- Recruiting
Medisch Spectrum Twente
Enschede
Angelique Sijben, MD, a.sijben@mst.nl
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
Johan AF Koekkoek, MD, PhD, 0031715269111, j.a.f.koekkoek@lumc.nl
- Recruiting
Erasmus Medical Center
Rotterdam, 3008 AE
Joost Jongen, MD, PhD, 0031107040704, j.jongen@erasmusmc.nl
- Recruiting
Haaglanden Medical Center
The Hague, 2501 CK
Lara Fritz, 0031703302000, l.fritz@haaglandenmc.nl
About this study
Official title: Seizure Treatment IN Glioma (STING): Comparing a Treatment Strategy With Levetiracetam Versus Treatment With Valproic Acid in Glioma Patients With a First Seizure
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.
Read the 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.
- Conditions
- Glioma
- Being tested
- Levetiracetam, Valproic Acid
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevetiracetamDrug
Also called Keppra
Antiepileptic drug levetiracetam
Valproic AcidDrug
Also called Depakine
Antiepileptic drug valproic acid
| Study group | Role | What they receive |
|---|---|---|
| Levetiracetam | Active comparator | 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. Receives: Drug: Levetiracetam |
| Valproic acid | Active comparator | 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. Receives: Drug: Valproic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ongoing seizure freedom at 6 months
The percentage of patients with ongoing seizure freedom at 6 months
Measured: 6 months
Secondary outcomes (13)
Cumulative incidence of treatment failure for any reason
Cumulative incidence function of time to treatment failure for any reason of ASM treatment using competing risk models with death as a competing event.
Measured: 36 months
Cumulative incidence of treatment failure for specific reasons
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
Measured: 36 months
Cumulative incidence of a first recurrent seizure
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.
Measured: 36 months
Adverse effects of the treatment
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
Measured: 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
Hospitalisation rate
hospitalization rate due to treatment failure
Measured: 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
Health-related quality of life
Health-related quality of life
Measured: 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
Cognitive complaints using MOS-CFS scores
Measured: 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
Mood
Anxiety and depression using HADS scale scores
Measured: 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
Performance Status
Karnofsky Performance Status Score
Measured: 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
Epilepsy burden
Measured: 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
Treatment response
Treatment response (e.g., maximum dosage of AED, use of add-on AED)
Measured: 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
Progression-free survival
Measured: 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
Overall survival
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start1 Feb 2018
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Center Haaglanden, Erasmus Medical Center, Amsterdam UMC, location VUmc
- Responsible party
- Principal investigator, j.a.f.koekkoek, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03048084
- Sponsor's protocol ID
- 77353
- Acronym
- STING
- Status last verified
- Aug 2026
- First submitted
- 7 Feb 2017
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van der Meer PB, Taphoorn MJB, Koekkoek JAF. Management of epilepsy in brain tumor patients. Curr Opin Oncol. 2022 Nov 1;34(6):685-690. doi: 10.1097/CCO.0000000000000876. Epub 2022 Jul 16.
PubMed 35838207Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.
PubMed 34171339
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Seizure Treatment IN Glioma (STING): Comparing a Treatment Strategy With Levetiracetam Versus Treatment With Valproic Acid in Glioma Patients With a First Seizure
- ClinicalTrials.gov ID
- NCT03048084
- Acronym / sponsor ID
- STING / 77353
- Conditions
- Glioma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Medical Center Haaglanden, Erasmus Medical Center, Amsterdam UMC, location VUmc
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam | Active comparator | Drug: LevetiracetamPatients 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 | Active comparator | Drug: Valproic AcidPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevetiracetamAlso: KeppraAntiepileptic drug levetiracetam | Drug | Levetiracetam |
| Valproic AcidAlso: DepakineAntiepileptic drug valproic acid | Drug | Valproic acid |
Primary outcome
Ongoing seizure freedom at 6 months
Time frame: 6 months
The percentage of patients with ongoing seizure freedom at 6 months
13 secondary outcomes
Cumulative incidence of treatment failure for any reason
Time frame: 36 months
Cumulative incidence of treatment failure for specific reasons
Time frame: 36 months
Cumulative incidence of a first recurrent seizure
Time frame: 36 months
Adverse effects of the treatment
Time frame: 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
Hospitalisation rate
Time frame: 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
Health-related quality of life
Time frame: 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
Time frame: 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
Mood
Time frame: 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
Performance Status
Time frame: 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
Time frame: 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
Treatment response
Time frame: 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
Time frame: 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 frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Derived from this study: PubMed 35838207van der Meer PB, Taphoorn MJB, Koekkoek JAF. Management of epilepsy in brain tumor patients. Curr Opin Oncol. 2022 Nov 1;34(6):685-690. doi: 10.1097/CCO.0000000000000876. Epub 2022 Jul 16.
- Derived from this study: PubMed 34171339Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levetiracetam and Valproic Acid in people with Glioma, run by Leiden University Medical Center at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johan AF Koekkoek, MD, PhD (0031715269111, j.a.f.koekkoek@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ongoing seizure freedom at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03048084, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.