The Tolerability of Saracatinib in Subjects With Lymphangioleiomyomatosis (LAM) (SLAM-1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Dose Determination
研究概览
简要总结
Lymphangioleiomyomatosis (LAM) is a rare lung disease that mostly affects women of childbearing age. In LAM, abnormal, muscle-like cells begin to grow out of control in the lungs. As a result, air can't move freely in and out of the lungs. In some cases, this means the lungs can't supply the body's other organs with enough oxygen.
This study is being conducted to find out what dose of a drug called saracatinib is best tolerated by people with LAM. This drug has been tested in patients with certain types of cancer but is not currently approved by the United States Food and Drug Administration (FDA). Saracatinib may work in cancer by preventing the growth, movement and invasiveness of cancer cells. The use of saracatinib to treat LAM is considered experimental. Preliminary testing already completed suggests that the study drug, saracatinib, may suppress certain substances in the lungs of patients with LAM thus may be effective in slowing down the disease process
详细描述
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or tuberous sclerosis complex 2 (TSC2) tumor suppressor genes. TSC is characterized by tumors in a wide range of tissues, seizures, mental retardation, autism, and organ failure. Lymphangioleiomyomatosis (LAM), the major pulmonary manifestation in women with TSC, is a progressive lung disease characterized by infiltration of atypical smooth muscle like cells and formation of cysts.
The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. Our preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in laboratory cultured cells.
The focus of this study is to examine if Src inhibition represents a potential therapeutic strategy in LAM. In this study, we will evaluate the safety, tolerability of Src inhibition in subjects with LAM.
The Quality Assurance (QA) plan is put forth in the Manual of Operations for this study. This study is utilizing the services of the Data Coordinating Center (DCC) at the University of Southern Florida. The data collected and entered in the electronic clinical research form (CRF) at each site will be reviewed by the site clinical research associate and the DCC data manager. Data check will be made throughout the study for all 3 sites and for all patients enrolled. Data checks to compare data entered into the registry against predefined rules for range or consistency with other data fields in the registry.
Source data verification will be done to assess the accuracy, completeness, or representativeness of registry data. This will be done by a DCC Clinical Research Associate (CRA).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients. It should be noted, however, that LAM occurs predominantly in women.
- •18 to 65 years of age.
- •All patients must have a diagnosis of LAM as defined by one of the following:
- •Open lung, transbronchial or thoracic needle biopsy consistent with LAM Open or needle abdominal biopsy findings consistent with LAM Computed tomography (CT) of chest or abdomen consistent with LAM in the setting of TSC, renal angiomyolipoma (AML), cystic abdominal lymphangiomas, or history of chylous effusion in the chest or abdomen CT of chest consistent with LAM plus serum vascular endothelial growth factor (VEGF-D) > 800 pg/ml In cases where the diagnosis of LAM is based on biopsy, review of the pathology specimens by pathologists who are experienced with LAM, such as those at the NIH or the Mayo Clinic, will be obtained (if not done so previously).
排除标准
- •Current infection.
- •Major surgery within the past 2 months
- •Advanced hematologic, renal, hepatic, or metabolic diseases
- •The use of another investigational drug within 30 days
- •The use of mammalian target of rapamycin (mTOR) inhibitors within 30 days
- •Previous lung transplantation or active on transplant list.
- •Inability to attend scheduled clinic visits
- •Inability to give informed consent
- •Inability to perform pulmonary function testing
- •History of malignancy in the past two years, other than squamous or basal cell skin cancer or mild cervical cancer.
- •Nursing mothers
- •Current or planned pregnancy.
- •Not using adequate contraception (in woman of childbearing potential).
- •Significant clinical change in health in the past 30 days
研究组 & 干预措施
Saracatinib
Only one arm: Intervention is Saracatinib. We plan to study three escalating doses of oral saracatinib; 50, 125 and 175 mg. Saracatinib is given orally once a day.
More regarding dose escalation is included in intervention below.
干预措施: Saracatinib (Drug)
结局指标
主要结局
Dose Determination
时间窗: Saracatinib will be given for 4 weeks, the subject will be followed for a total of 8 weeks.
One of three escalating daily oral doses of saracatinib; 50, 125 and 175 mg. Saracatinib will be given orally once a day for four weeks. Adverse events will be monitored. The subject will receive only one of the doses as determined by the escalation of the study.
次要结局
- Safety Profile(8 weeks)
研究者
Tony Eissa
Professor of Medicine - Pulmonary
Baylor College of Medicine