A Safety and Feasibility Study of Minocycline Therapy for Management of Adverse Radiation Effects After Brain Metastases Radiosurgery
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Monitoring for adverse effects of Minocycline
研究概览
简要总结
Stereotactic radiosurgery (SRS) is a well-established treatment for patients with metastatic brain tumors. Although SRS has a very high tumor growth control these interventions are associated with adverse radiation effects (ARE) in approximately 15 % of patients. The traditional approach, and still a mainstay, is the administration of a course of high dose anti-inflammatory corticosteroids. Currently there are no other effective oral neuroprotective agents in clinical practice which can improve outcomes of patients with ARE after radiosurgery for brain metastases.
Minocycline, an antibiotic with a favorable adverse effect profile and pharmacokinetics, has been shown to have neuroprotective properties in experimental models of a variety of neurological diseases, as well as in human clinical trials. The investigators propose a single arm clinical trial, to evaluate the safety and feasibility of minocycline in improving ARE. This study will recruit 15 patients who will be treated with minocycline (100mg BID) for 3 months. This clinical trial has the potential to prove that minocycline therapy is safe in this patient population. In addition, positive results will provide preliminary evidence for its use in an array of radiosurgical indications.
详细描述
Although stereotactic radiosurgery (SRS) has proven to be highly effective in the management of brain metastases, it is not without risk. Despite selective targeting of lesions and the sharp dose fall-off associated with radiosurgical treatments, adverse radiation effects (AREs) can occur in 10-15% of patients. Adverse radiation effects (AREs) can be defined as unexpected or undesirable post-radiosurgery imaging change regardless of whether it is clinically symptomatic. Patients showing ARE have limited therapeutic options with corticosteroids being the main treatment modality. This single arm clinical trial, will evaluate the safety and feasibility of minocycline in improving AREs. Brain metastases patients with documented AREs will be treated with minocycline (100 mg twice a day) for 3 months in addition to the standard treatment with oral corticosteroids. The investigators anticipate recruiting a total of 15 patients over 12 months.
Primary aim:
The primary aim is of this study to evaluate safety and feasibility of minocycline therapy in patients with ARE after radiosurgery. The investigators' hypothesis is that minocycline will be safe in this patient population. Safety will be assessed by monitoring blood levels of drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects.
Research Strategy The investigators plan to conduct a single arm observational study to evaluate safety and feasibility of minocycline in patients diagnosed with radiosurgery associated adverse radiation effects. In addition to clinical and biochemical monitoring for safety, the investigators will also employ neuroimaging techniques to investigate whether minocycline reduces enhancement at lesion in post contrast T1 weighted MRI and reduces hyper intensity surrounding the tumor as detected by T2 MRI radiosurgery.
Primary Outcomes: 1) The primary clinical outcome will be safety of minocycline use in this patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range: 18 - 90 years
- •Males and females.
- •Patients must have undergone cranial radiosurgery.
- •MRI evidence supporting the diagnosis of ARE and/or surgical biopsy evidence of necrosis without tumor at ≤2 months before study entry.
- •Karnofsky performance status of ≥60,
- •With or without evidence of progressive neurologic signs or symptoms appropriate to the location of the ARE, and no previous bevacizumab therapy.
- •With or without previous chemotherapy for their tumor.
- •Routine laboratory study results with bilirubin ≤1.5 times the upper limit of normal, aspartate aminotransferase and/or alanine aminotransferase <2.5 times the upper limit of normal, creatinine <2.0 times the upper limit of normal.
- •Patients with a history of seizures will be required to be receiving anticonvulsant therapy and to be seizure-free for ≥1 week before study.
排除标准
- •Significant mass effect requiring resection (as assessed by a clinical neurosurgeon)
- •Known hypersensitivity to tetracyclines
- •Women of childbearing age must be non-lactating and have a negative urine pregnancy test (adequate birth control includes use of intra uterine device, or a barrier method, e.g. condom, diaphragm). The results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues, having potentially toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryo toxicity has been noted in animals treated early in pregnancy. Therefore pregnant women will not be allowed to participate in this study
- •Female subjects on oral contraceptives
- •Contraindication to undergo MRI
- •Significant cardiopulmonary, renal or neurological co-morbidities
- •Current diagnosis of major depression, substance abuse, or other psychiatric disorders;
研究组 & 干预措施
Minocycline
oral Minocycline 100 mg twice a day for 3 months.
干预措施: Minocycline (Drug)
结局指标
主要结局
Monitoring for adverse effects of Minocycline
时间窗: 3 months
Safety will be assessed by monitoring blood levels of drug, liver enzymes, renal function tests, and monitoring for major and minor side-effects.
次要结局
- Monitoring for imaging improvement(3 months)
研究者
Ajay Niranjan
Associate Professor
University of Pittsburgh