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Seizure Treatment in Glioma (STING)

Primary Purpose

Glioma

Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Levetiracetam
Valproic Acid
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VU University Medical CenterRecruiting
  • Medisch Spectrum TwenteRecruiting
  • Leiden University Medical CenterRecruiting
  • Erasmus Medical CenterRecruiting
  • Haaglanden Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Levetiracetam

Valproic acid

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Ongoing seizure freedom at 6 months
The percentage of patients with ongoing seizure freedom at 6 months

Secondary Outcome Measures

Time to 6 months seizure freedom
Time to 6 months seizure freedom
Seizure outcome at 12 months
Seizure outcome at 12 months
Adverse effects of the treatment
Adverse effects of the treatment
Hospitalisation rate
hospitalization rate due to treatment failure
Health-related quality of life
Health-related quality of life
Cognitive complaints
Cognitive complaints
Mood
Anxiety and depression
Performance Status
Karnofsky Performance Status Score
Epilepsy burden
Epilepsy burden
Treatment response
Treatment response (e.g., maximum dosage of AED, use of add-on AED)
Progression-free survival
Progression-free survival
Overall survival
Overall survival

Full Information

First Posted
February 7, 2017
Last Updated
March 7, 2023
Sponsor
Leiden University Medical Center
Collaborators
Medical Center Haaglanden, Erasmus Medical Center, Amsterdam UMC, location VUmc
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1. Study Identification

Unique Protocol Identification Number
NCT03048084
Brief Title
Seizure Treatment in Glioma
Acronym
STING
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2018 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
Collaborators
Medical Center Haaglanden, Erasmus Medical Center, Amsterdam UMC, location VUmc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Levetiracetam
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Valproic acid
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Levetiracetam
Other Intervention Name(s)
Keppra
Intervention Description
Antiepileptic drug levetiracetam
Intervention Type
Drug
Intervention Name(s)
Valproic Acid
Other Intervention Name(s)
Depakine
Intervention Description
Antiepileptic drug valproic acid
Primary Outcome Measure Information:
Title
Ongoing seizure freedom at 6 months
Description
The percentage of patients with ongoing seizure freedom at 6 months
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Time to 6 months seizure freedom
Description
Time to 6 months seizure freedom
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
Title
Seizure outcome at 12 months
Description
Seizure outcome at 12 months
Time Frame
12 months
Title
Adverse effects of the treatment
Description
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
Title
Hospitalisation rate
Description
hospitalization rate due to treatment failure
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
Title
Health-related quality of life
Description
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
Title
Cognitive complaints
Description
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
Title
Mood
Description
Anxiety and depression
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
Title
Performance Status
Description
Karnofsky Performance Status Score
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
Title
Epilepsy burden
Description
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
Title
Treatment response
Description
Treatment response (e.g., maximum dosage of AED, use of add-on AED)
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
Title
Progression-free survival
Description
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
Title
Overall survival
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johan AF Koekkoek, MD, PhD
Phone
0031715269111
Email
j.a.f.koekkoek@lumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Linda Dirven, PhD
Phone
0031715296735
Email
l.dirven@lumc.nl
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1007 MB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jaap C Reijneveld, MD, PhD
Phone
0031204442834
Email
jc.reijneveld@vumc.nl
Facility Name
Medisch Spectrum Twente
City
Enschede
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthijs Van der Meulen, MD
Email
matthijs.vandermeulen@mst.nl
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan AF Koekkoek, MD, PhD
Phone
0031715269111
Email
j.a.f.koekkoek@lumc.nl
Facility Name
Erasmus Medical Center
City
Rotterdam
ZIP/Postal Code
3008 AE
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin J van den Bent, MD, PhD
Phone
0031107040704
Email
m.vandenbent@erasmusmc.nl
Facility Name
Haaglanden Medical Center
City
The Hague
ZIP/Postal Code
2501 CK
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin JB Taphoorn, MD, PhD
Phone
0031703302000
Email
m.taphoorn@haaglandenmc.nl

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34171339
Citation
Lang 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.
Results Reference
derived

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Seizure Treatment in Glioma

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