Multicenter clinical trials for TSC & related disorders

TSC 多中心临床试验

基本信息

批准号：
7214642
负责人：
SANDRA L DABORA
金额：
$ 33.23万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7214642
关键词：
Adult Aftercare Angiofibroma Angiomyolipoma Biological Markers Blood Brain Clinic Clinical Trials Clinical Trials Design Cystic kidney DNA Data Defect Development Disease End Point Enrollment Face Foundations Future Genotype Goals International Kidney Lesion Lung diseases Lymphangioleiomyomatosis Molecular Patient Care Patients Pharmaceutical Preparations Phase II Clinical Trials Population Protocols documentation Renal Angiomyolipoma Research Safety Sampling Series Serum Sirolimus Skin Standards of Weights and Measures Subependymal Giant Cell Astrocytoma Suppressor Genes Syndrome Systemic Therapy Therapeutic Translational Research Tuberous Sclerosis United States National Institutes of Health Urine design follow-up improved interest mTOR Inhibitor mTOR Signaling Pathway novel strategies pulmonary function response therapeutic target translational medicine tumor

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to implement the first multicenter clinical trial for the multisystem familial tumor disorder, tuberous sclerosis (TSC). TSC is tumor a suppressor gene disorder with autosomal dominant inheritance in which hamartomatous lesions occur frequently in the kidneys, brain and skin. Because of recent research advances in TSC, there is substantial data suggesting the mTOR inhibitor, rapamycin, may provide therapeutic benefit in TSC. Treatment options for manifestations of TSC are limited and there are no drugs currently available that treat the underlying defect in TSC, so there is great interest in the development of such targeted therapeutic approaches. We have organized 6 leading TSC clinics into a consortium for implementing the first multicenter clinical trial for TSC, a phase II trial of rapamycin for the treatment of kidney angiomyolipomas associated with TSC and the related pulmonary disorder, lymphangioleiomyomatosis (LAM). Although the focus of this proposal is almost entirely on an initial phase II trial, our longer term goal is for this to be the first of many well designed multicenter clinical trials aimed at developing novel approaches to systemic therapy for TSC and related disorders. This project is consistent with NIH goals for TSC research and the NIH roadmap initiative on translational research. The specific aims of this project are: 1) Determine the efficacy of rapamycin for the treatment of kidney angiomyolipomas (AMLs) in adult patients with TSC or LAM; 2) Determine the safety profile of using rapamycin in this patient population; 3) Collect data on long term follow up of kidney AMLs for 12 months after treatment on this study is discontinued; 4) Evaluate other TSC lesions (tubers, subependymal giant cell astrocytomas, facial angiofibromas, kidney cysts) and pulmonary disease in LAM patients for evidence of response to treatment; 5) Collect blood DNA, serum and urine samples periodically during this study for genotype analyses and biomarker studies; 6) Determine clinical trial priorities for subsequent trials and initiate the design and implementation of these protocols.

描述（由申请人提供）：该项目的目标是针对多系统家族性肿瘤疾病结节性硬化症（TSC）实施第一个多中心临床试验。 TSC 是一种常染色体显性遗传的抑制基因疾病，其中错构瘤病变常发生于肾脏、大脑和皮肤。由于 TSC 的最新研究进展，大量数据表明 mTOR 抑制剂雷帕霉素可能为 TSC 提供治疗益处。 TSC 表现的治疗选择有限，并且目前没有药物可以治疗 TSC 的潜在缺陷，因此人们对开发此类靶向治疗方法非常感兴趣。我们已将 6 家领先的 TSC 诊所组织成一个联盟，以实施第一个 TSC 多中心临床试验，这是一项雷帕霉素治疗与 TSC 相关的肾血管平滑肌脂肪瘤和相关肺部疾病淋巴管平滑肌瘤病 (LAM) 的 II 期试验。尽管该提案的重点几乎完全集中在初始 II 期试验上，但我们的长期目标是成为许多精心设计的多中心临床试验中的第一个，旨在开发针对 TSC 和相关疾病的系统治疗的新方法。该项目与 NIH TSC 研究目标和 NIH 转化研究路线图倡议一致。该项目的具体目标是： 1) 确定雷帕霉素治疗成人 TSC 或 LAM 患者肾血管平滑肌脂肪瘤 (AML) 的疗效； 2) 确定在该患者群体中使用雷帕霉素的安全性； 3) 收集本研究治疗停止后 12 个月的肾脏 AML 长期随访数据； 4) 评估 LAM 患者的其他 TSC 病变（结节、室管膜下巨细胞星形细胞瘤、面部血管纤维瘤、肾囊肿）和肺部疾病，以获得治疗反应的证据； 5）本研究期间定期采集血液DNA、血清和尿液样本，用于基因型分析和生物标志物研究； 6) 确定后续试验的临床试验优先顺序，并启动这些方案的设计和实施。