Short Versus Long-term Levetiracetam in Brain Tumors

Seizures Clinical Trial

— LIBRA  

Official title:

Short Versus Long-term Levetiracetam in Brain Tumors: A Phase 3 Randomized Controlled Trial (LIBRA)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06442748
• Other study ID #: 4385
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2024
• Est. completion date: June 1, 2031

Study information

• Verified date: May 2024
• Source: Tata Memorial Centre
• Contact: Archya Dasgupta, MD
• Phone: 02224177000
• Email: archya1010[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 604
• Est. completion date: June 1, 2031
• Est. primary completion date: June 1, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors
• Seizures

Intervention

Drug:
• Levetiracetam
Levetiracetam is usually preferred in brain tumor-related epilepsy. Levetiracetam is a second-generation antiepileptic drug that binds to synaptic vesicle glycoprotein SV2A, which interferes with the release of neurotransmitters from the synaptic vesicle and control seizure by multiple mechanisms.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tata Memorial Centre

References & Publications (27)

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year seizure free survival	Seizure-free survival measured using Kaplan-Meier product limit method survival calculated from the time of randomization.	7 year
Secondary	Overall survival	Overall survival calculated using Kaplan-Meier product-limit method. Death from any cause will be considered as an event.	7 year
Secondary	Progression-free survival	Progression-free survival calculated using Kaplan-Meier product-limit method. Date of radiological progression will be considered as an event.	7 year
Secondary	Cost-benefit analysis Cost-benefit analysis	Cumulative cost of antiepileptic medications and cost of management of seizures between the two groups will be compared using proportions of expenditure.	7 year
Secondary	Quality of life core questionnaire	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.	7 year
Secondary	Quality of life brain cancer module	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.	7 year