Phase II Study of Rapamycin for Complicated Vascular Anomalies IND Exempt

雷帕霉素治疗复杂血管异常的 II 期研究 IND 豁免

• 批准号: 7937063
• 负责人: Denise Martin Adams
• 金额: $ 33.89万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937063
• 关键词: Phase; II; Study; Rapamycin; Complicated

DESCRIPTION (provided by applicant): Patients with vascular anomalies (VA) have a spectrum of diseases that can be broadly classified into vascular tumors and malformations. Complicated vascular anomalies can cause disfigurement, chronic pain, and organ dysfunction with significant morbidity and mortality. Despite the severity of potential complications, there is a lack of uniform guidelines for the treatment and response to treatment of children and young adults with these diseases. There are preclinical and clinical data supporting the essential regulatory function of the phosphatidylinositol-3-kinase/Protein Kinase B /mammalian target of rapamycin (PI 3-kinase/Akt/mTOR) pathway in vascular growth and organization and suggest a therapeutic target for patients with complicated vascular anomalies. The overall goal of this trial is to objectively determine the effectiveness and safety of the mTOR inhibitor rapamycin in the treatment of children and young adults diagnosed with complicated vascular anomalies. The applicant proposes a Phase 2 trial with the diagnostic, therapeutic and response criteria experimentally determined in this study used as a framework for future Phase 3 clinical trials. It is hypothesized that Rapamycin treatment of children and young adults with complicated vascular anomalies will prove to be safe and provide objective disease response resulting in improved clinical status and quality of life. The primary aim is to determine the efficacy of oral rapamycin in children and young adults with complicated vascular anomalies. For this purpose, 60 patients with complicated vascular anomalies who meet criteria for systemic treatment will receive oral rapamycin. Serum drug levels will be monitored with a target range of 10-15 ng/mL. Disease response will be assessed at 3, 6 and 12 months using radiographic, clinical and quality of life measures. In addition, the safety of oral rapamycin in children and young adults with complicated vascular anomalies will be determined. Toxicities will be assessed and recorded at specific intervals throughout therapy. Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) will be used to categorize and grade all toxicities. Safety monitoring and stopping rules will be instituted to ensure that serious treatment-related toxicities are reported and study continuation re-evaluated. The secondary aims are to assess biomarker analysis on serum and tissue from children and young adults with vascular anomalies. Biomarkers will be tested at baseline, 6 months and 12 months on a limited number of subjects.

描述（由申请人提供）： 血管异常（VA）患者患有一系列疾病，可大致分为血管肿瘤和畸形。 复杂的血管异常可导致毁容、慢性疼痛和器官功能障碍，并具有显着的发病率和死亡率。 尽管潜在并发症很严重，但对于患有这些疾病的儿童和年轻人的治疗和治疗反应缺乏统一的指南。 临床前和临床数据支持磷脂酰肌醇 3 激酶/蛋白激酶 B/雷帕霉素哺乳动物靶点 (PI 3 激酶/Akt/mTOR) 通路在血管生长和组织中的基本调节功能，并为患者提出了治疗靶点伴有复杂的血管异常。 该试验的总体目标是客观地确定 mTOR 抑制剂雷帕霉素在治疗诊断为复杂血管异常的儿童和年轻人中的有效性和安全性。 申请人提出了一项 2 期试验，其诊断、治疗和反应标准在本研究中通过实验确定，用作未来 3 期临床试验的框架。 据推测，雷帕霉素治疗患有复杂血管异常的儿童和年轻人将被证明是安全的，并提供客观的疾病反应，从而改善临床状态和生活质量。 主要目的是确定口服雷帕霉素对患有复杂血管异常的儿童和年轻人的疗效。 为此，60 名符合全身治疗标准的复杂血管异常患者将接受口服雷帕霉素治疗。 血清药物水平的监测目标范围为 10-15 ng/mL。 将在第 3、6 和 12 个月时使用放射学、临床和生活质量指标评估疾病反应。 此外，还将确定口服雷帕霉素对于患有复杂血管异常的儿童和年轻人的安全性。 在整个治疗过程中，将按照特定的时间间隔评估和记录毒性。 不良事件通用术语标准（CTCAE，3.0 版）将用于对所有毒性进行分类和分级。 将制定安全监测和停止规则，以确保报告与治疗相关的严重毒性并重新评估研究的持续性。 次要目标是评估患有血管异常的儿童和年轻人的血清和组织的生物标志物分析。 生物标志物将在基线、6 个月和 12 个月时对有限数量的受试者进行测试。