A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as lithium, may protect normal cells from the side effects of radiation therapy. Giving lithium together with radiation therapy may allow a higher dose of radiation therapy to be given so that more tumor cells are killed.
PURPOSE: This phase I trial is studying the side effects and best dose of lithium when given together with whole-brain radiation therapy in treating patients with brain metastases from primary cancer outside the brain.
详细描述
OBJECTIVES:
- Determine the feasibility of concurrent lithium carbonate and whole-brain radiotherapy, as measured by safety and compliance, in patients with primary extracranial malignancy and brain metastases.
OUTLINE: This is an open-label, dose-escalation study of lithium carbonate.
Patients receive oral lithium carbonate twice daily on days 1-7 and 2-4 times daily on days 8-21. Patients undergo whole-brain radiotherapy once daily on days 8-12 and 15-19.
Cohorts of 3-6 patients receive escalating doses of lithium carbonate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histopathologically confirmed extracranial primary malignancy
- •Multiple (i.e., > 3) brain metastases OR < 3 metastases with at least 1 metastasis > 4.0 cm in diameter
- •Not eligible for radiosurgery
- •No requirement for immediate whole-brain radiotherapy
- •No metastases to the midbrain or brainstem
排除标准
- •Zubrod performance status 0-2
- •Life expectancy ≥ 8 weeks
- •Platelet count > 100,000/mm^3
- •ANC > 1,500/mm^3
- •Hemoglobin ≥ 10 g/dL
- •BUN < 25 mg/dL
- •Creatinine < 1.5 mg/dL
- •Bilirubin < 1.5 mg/dL
- •ALT ≤ 2 times normal
- •Sodium > 136 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Neurologically stable
- •No seizure disorders or seizures due to brain metastases
- •No medical illnesses or psychiatric conditions that would preclude completion of study treatment
- •No sensory neuropathy ≥ grade 2
- •No bipolar disorder
- •No thyroid disease
- •No QTc interval prolongation
- •PRIOR CONCURRENT THERAPY:
- •More than 2 weeks since prior and no concurrent chemotherapy
- •At least 2 weeks since prior and no concurrent NSAIDs, angiotensin-converting enzyme inhibitors (e.g., enalapril or captopril), calcium channel blockers, diuretics, selective cyclooxygenase-2 inhibitors, acetazolamide, urea, xanthine, or alkalinizing agents (e.g., sodium bicarbonate)
- •No prior radiotherapy to the head and neck area
- •No prior radiosurgery
- •No concurrent radiotherapy to other sites
- •No concurrent anticonvulsants due to brain metastases
- •No concurrent psychoactive drugs
- •No concurrent thyroid medications
- •No concurrent amifostine
研究组 & 干预措施
Therapeutic Intervention
干预措施: lithium carbonate (Drug)
Therapeutic Intervention
干预措施: cognitive assessment (Procedure)
Therapeutic Intervention
干预措施: quality-of-life assessment (Procedure)
Therapeutic Intervention
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance
时间窗: Safety is measured by the rate of grade 3 or worse
次要结局
未报告次要终点
研究者
David Gius, MD, PhD
Professor; Radiation Oncologist
Vanderbilt-Ingram Cancer Center