A Phase II Randomized Open-Label Trial of Levetiracetam for Prevention of Seizures in Patients With Brain Metastases in Primary Motor Cortex
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Seizure Rate
研究概览
简要总结
This is a randomized trial for patients with brain metastases in the primary motor cortex who have not had seizures to receive either the prophylactic anti-seizure medication levetiracetam (also known by its trade name Keppra) or proceed with standard of care management, which does not currently include prophylactic levetiracetam. Patients who enroll to this trial will be randomized to receive prophylactic levetiracetam or not receive prophylactic levetiracetam.
详细描述
Brain metastases (BrM) impact 10%-40% of patients with solid malignancies and are associated with significant clinical sequelae, including development of seizures. The development of seizures has the potential for significant detriment on patient quality of life. The goal of this study is to evaluate the role of levetiracetam as primary prophylaxis in seizure-naïve patients with metastases in primary motor cortex, an area at high risk of seizures. Patients will be randomized to receive levetiracetam/ASM or to receive no ASM therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a biopsy proven solid malignancy with at least one intracranial lesion radiographically consistent with or pathologically proven to be a brain metastasis located in the primary motor cortex measuring 0.5 cm or larger in maximal unidimensional size
- •Age of at least 18 years
- •Karnofsky performance status of at least 60
- •Estimated survival of at least 3-6 months in the opinion of the enrolling clinician and/or study PI
- •Ability to understand and the willingness to sign a written informed consent document by either ink on paper or a DF/HCC approved eConsent medium
排除标准
- •Participants with prior seizures as this is a study for seizure naïve patients
- •Participants with an allergy to levetiracetam as levetiracetam is the prophylactic anti-seizure medication under study
- •Participants concurrently taking (i.e. at enrollment) an ASM for non-seizure indications at clinically relevant doses (gabapentin 1800 mg/day or higher, pregabalin 300 mg/ day or higher, lamotrigine 150 mg/ day or higher, valproic acid 1000 mg/ day or higher, topiramate 200 mg/ day or higher, carbamazepine 200 mg/ day or higher, oxcarbazepine 300 mg/ day or higher, primidone 100 mg/day or higher) because use of these medications could bias the study toward the null
- •Participants who cannot tolerate a magnetic resonance imaging (MRI) study of the brain, which is required to determine the presence of and follow the course of brain metastases under study
- •Participants who cannot receive gadolinium as MRI of the brain with contrast is required
- •Participants with end stage renal disease due to risk of nephrogenic systemic fibrosis in this patient population after exposure to gadolinium-based contrast agents
- •Participants with widespread, definitive leptomeningeal disease given that leptomeningeal disease and brain metastases are different entities
- •Pregnant women are excluded from this study because levetiracetam crosses the placenta. In addition, the potential deleterious effects of gadolinium on the developing fetus are not completely known
- •Women who are breastfeeding are excluded from this study because levetiracetam enters breast milk. In addition, the potential deleterious effects of gadolinium in breast milk remain unknown
研究组 & 干预措施
No Prophylactic Levetiracetam
No Anti-Seizure Medication
Prophylactic Levetiracetam
Levetiracetam Anti-Seizure Medication
干预措施: Levetiracetam (Keppra) (Drug)
结局指标
主要结局
Seizure Rate
时间窗: Duration of time on study (estimated 1 year)
To determine whether seizure rate is lower in seizure-naïve patients with brain metastases in primary motor cortex with levetiracetam prophylaxis versus usual care of no ASM therapy.
次要结局
- Time to development of leptomeningeal disease(Duration of time on study (estimated 1 year))
- Time to craniotomy(Duration of time on study (estimated 1 year))
- Time to radiotherapeutic treatments after initial management(Duration of time on study (estimated 1 year))
- Progression free survival(Duration of time on study (estimated 1 year))
- Time to detection of new brain metastases(Duration of time on study (estimated 1 year))
- Quality of life/symptom burden and interference(Duration of time on study (estimated 1 year))
- Seizure type(Duration of time on study (estimated 1 year))
- Time to seizure(Duration of time on study (estimated 1 year))
- Seizure rate in the week following brain-directed local therapy such as brain-directed surgery or radiation(Duration of time on study (estimated 1 year))
- Time to seizure(Duration of time on study (estimated 1 year))
- Overall survival(Duration of time on study (estimated 1 year))
- Death due to neurologic disease progression(Duration of time on study (estimated 1 year))
- Progression free survival(Duration of time on study (estimated 1 year))
- Performance status(Duration of time on study (estimated 1 year))
- Time to development of radiation necrosis(Duration of time on study (estimated 1 year))
- Time to development of leptomeningeal disease(Duration of time on study (estimated 1 year))
- Time to local recurrence(Duration of time on study (estimated 1 year))
- Time to craniotomy(Duration of time on study (estimated 1 year))
- Time to detection of new brain metastases(Duration of time on study (estimated 1 year))
- Quality of life/symptom burden and interference(Duration of time on study (estimated 1 year))
- Time to radiotherapeutic treatments after initial management(Duration of time on study (estimated 1 year))
- Seizure type(Duration of time on study (estimated 1 year))
- Seizure rate in the week following brain-directed local therapy such as brain-directed surgery or radiation(Duration of time on study (estimated 1 year))
- Time to secondary seizures(Duration of time on study (estimated 1 year))
研究者
Ayal A. Aizer, MD
Director, Central Nervous System Radiation Oncology; Associate Professor, Harvard Medical School
Brigham and Women's Hospital