Arginine With Whole Brain Radiation Therapy for the Treatment of Brain Metastases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Peak plasma L-arginine (arginine) and arginine metabolite concentration
研究概览
简要总结
This early phase I trial evaluates different administration techniques (oral or intravenous) for arginine and tests the safety of giving arginine with whole brain radiation therapy in patients who have cancer that has spread from where it first started (primary site) to the brain (brain metastases). Arginine is an essential amino acid. Amino acids are the molecules that join together to form proteins in the body. Arginine supplementation has been shown to improve how brain metastases respond to radiation therapy. The optimal dosing of arginine for this purpose has not been determined. This study measures the level of arginine in the blood with oral and intravenous dosing at specific time intervals before and after drug administration to determine the best dosing strategy.
详细描述
PRIMARY OBJECTIVE:
I. Determine the bioavailability of orally-administered arginine (L-arginine).
SECONDARY OBJECTIVES:
I. Test the safety of daily arginine administration with standard-fractionation whole brain radiation therapy (WBRT).
II. Determine the side effect profile of oral and intravenous (IV) L-arginine. III. Quantify frontal cortex blood volume/flow changes following L-arginine (L-arg) administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Diagnosis of brain metastases from any primary cancer
- •Planned to undergo whole-brain radiation therapy (Hippocampal avoidant is ok)
- •No systemic anti-neoplastic agent concurrent with WBRT (memantine is ok)
- •Not inpatient at the time of treatment start
- •Age 18 or older
- •Able to consent for self
排除标准
- •Patient unwilling/unable to receive daily arginine treatment (IV or oral) for the 10 days of WBRT
- •Systemic therapy continuing during WBRT
- •Creatinine > 1.5 x the upper limit of normal
- •Alanine aminotransferase (ALT) > 6x the upper limit of normal
- •Patient planned to be treated as an inpatient
- •Age < 18 years
- •Adult not able to consent for self
- •Prisoners
- •Cognitively impaired/impaired decision-making capacity
研究组 & 干预措施
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Biospecimen Collection (Procedure)
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Computed Tomography (Procedure)
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Spectroscopy (Procedure)
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Whole-Brain Radiotherapy (Radiation)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Biospecimen Collection (Procedure)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Computed Tomography (Procedure)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Spectroscopy (Procedure)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Whole-Brain Radiotherapy (Radiation)
Arm B (oral L-arginine, WBRT)
Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Arginine (Dietary Supplement)
Arm A (IV L-arginine, WBRT)
Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.
干预措施: Arginine (Dietary Supplement)
结局指标
主要结局
Peak plasma L-arginine (arginine) and arginine metabolite concentration
时间窗: Within 4 hours of oral and intravenous (IV) dosing of L-arginine
By compartmental pharmacokinetic analysis, the plasma arginine levels at before administration, 10 min, 30 min, 1 hour, 2 hours, and 4 hours post administration will be used to estimate the median time to reach the peak plasma arginine and the mean value of peak. This will be done separately by two arms.
次要结局
- Incidence of adverse events associated with delivering L-arginine with standard fractionation whole brain radiation therapy(At 1 week into radiation and at completion of 2 week course)
- Side effect profile of oral and IV arginine(On days 1, 5, and 10)
- Describe The Immunological Effects of Oral versus IV Arginine(Up to 10 days)
- Frontal cortex blood volume/flow changes with L-arginine administration(Up to 1 year)
- Describe The Metabolic Effects of Oral versus IV Arginine(Up to 10 days)
研究者
Lisa Sudmeier
Principal Investigator
Emory University