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Short Versus Long-term Levetiracetam in Brain Tumors

Phase 3
Recruiting
Conditions
Seizures
Brain Tumors
Antiepileptics
Levetiracetam
Interventions
Registration Number
NCT06442748
Lead Sponsor
Tata Memorial Centre
Brief Summary

Levetiracetam is the commonly preferred anti-seizure medicine in patients with brain tumors. This drug has reduced the risk of seizure events occurring but is associated with a risk of side effects such as increased headache, drowsiness, loss of muscle coordination, and psychological challenges in patients. In patients undergoing appropriate treatment for brain tumors and controlled of seizures in the initial few months of levetiracetam, the chance of further seizures is relatively low. The optimal duration to give levetiracetam is not well defined for these patients, and currently as standard treatment levetiracetam is continued for 2-3 years. This study aims to answer this question by comparing patients on a short course of levetiracetam (experimental arm) versus a longer course of levetiracetam (standard arm), with the anticipation that a shorter duration of treatment will not lead to increased seizure episodes.

Detailed Description

Patients with prior history of seizure from primary brain tumor in the supratentorial location with controlled seizure on levetiracetam monotherapy for at least six months will be considered for the study. Patients more than 18 years of age with KPS ≥ 50 will be eligible. Patients will be randomized in one of the two arms (standard arm or experimental arm) in a 1:1 ratio and stratified based on seizure type, location, histology, tumor grade, and adjuvant therapy. Randomization will be done by the statistician via computerized software using a permuted block design. In the standard arm, patients will continue on the same dose and schedule of levetiracetam (typically prescribed in the range of 1000-3000 mg/ day in 2-3 divided doses) for a duration of 2 years. In the experimental arm, levetiracetam will be tapered by 250- 500 mg every week and stopped. Follow-ups will be done every 3-6 months as per standard practice for the given tumor histology. Neuroimaging will be done 6-12 monthly as per routine clinical practice. The quality-of-life assessment will be done every six months. The primary endpoint is 2-year seizure free survival calculated from the time of randomization.

Patients will continue to receive standard treatment, including adjuvant therapy as standard practice. In case in either arm, the patient develops a seizure episode after stopping levetiracetam will be restarted on levetiracetam monotherapy. If a patient develops a seizure episode while on levetiracetam monotherapy, further add-on antiepileptics will be considered as per standard practice by the responsible physician. Any complications arising from previous treatments (e.g., radio necrosis) or recurrent disease during the study period will be managed according to standard institutional practice without any influence of the study.

The study will be conducted at Tata Memorial Centre with a total sample size of 604 patients for a duration of seven years.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
604
Inclusion Criteria

• Age ≥ 18years

  • History of seizure
  • Histological diagnosis of primary brain tumor
  • Supratentorial location of primary tumor
  • Controlled on levetiracetam monotherapy for 6 months
  • Index surgery within 1 year
  • Karnofsky Performance Scale (KPS) ≥ 50
Exclusion Criteria
  • KPS < 50
  • No history of seizure
  • Unclear history of seizure episodes in the past
  • Use of antiepileptics other than levetiracetam in the previous 6 months
  • No histological diagnosis
  • Progressive disease
  • Brain metastasis
  • Altered mental status with deficits in understanding or inability to consent to the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EXPERIMENTALLevetiracetamIn the experimental arm, levetiracetam will be tapered by 250- 500 mg every week and then stopped.
STANDARDLevetiracetamIn the standard arm, patients will continue on the same dose and schedule of levetiracetam (prescribed in the range of 1000-3000 mg/ day in 2-3 divided doses) for a duration of 2 years.
Primary Outcome Measures
NameTimeMethod
2-year seizure free survival7 year

Seizure-free survival measured using Kaplan-Meier product limit method survival calculated from the time of randomization.

Secondary Outcome Measures
NameTimeMethod
Quality of life brain cancer module7 year

The European Organization for Research and Treatment of Cancer (EORTC) brain module (BN20) questionnaire will be used. The summary scores will be calculated from the raw scores as per the manual, ranging from 0 to 100, with higher scores representing better outcomes. The global score and scores of subdomains will be calculated during follow-up and compared with baseline.

Overall survival7 year

Overall survival calculated using Kaplan-Meier product-limit method. Death from any cause will be considered as an event.

Progression-free survival7 year

Progression-free survival calculated using Kaplan-Meier product-limit method. Date of radiological progression will be considered as an event.

Cost-benefit analysis Cost-benefit analysis7 year

Cumulative cost of antiepileptic medications and cost of management of seizures between the two groups will be compared using proportions of expenditure.

Quality of life core questionnaire7 year

The European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) core questionnaire (C30) will be used. The summary scores will be calculated from the raw scores as per the manual, ranging from 0 to 100, with higher scores representing better outcomes. The global score and scores of subdomains will be calculated during follow-up and compared with baseline.

Trial Locations

Locations (1)

Tata Memorial Centre

🇮🇳

Mumbai, Maharashtra, India

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