Phase 2 Study of Vincristine vs. Sirolimus for the Treatment of High Risk Kaposiform Hemangioendothelioma

长春新碱与西罗莫司治疗高危卡波西样血管内皮瘤的 2 期研究

• 批准号: 8925778
• 负责人: Denise Martin Adams
• 金额: $ 14.16万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925778
• 关键词: Phase; Study; Vincristine; vs.; Sirolimus

DESCRIPTION (provided by applicant): Kaposiform hemangioendotheliomas (KHE) are extremely rare life threatening tumors, which can be associated with Kasabach-Merritt phenomenon consisting of profound thrombocytopenia and hypofibrinogenemia, causing a significant risk of bleeding and an associated mortality rate as high as 20% to 30%. 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 tumors. KHE patients have been treated with a multitude of aggressive drug regimens without prospective evaluation of response or safety. Presently, vincristine is considered the standard of practice. A subset of these patients has been treated on study SIR-DA-0901, a Phase 2 trial assessing the efficacy and safety of sirolimus for the treatment of complicated vascular anomalies. Although the numbers are small, the response and tolerability to treatment have appeared promising. There are pre-clinical and clinical data supporting the essential regulatory function of the phosphoinositide-3-kinase/AKT/mammalian target of rapamycin (PI3 kinase/AKT/mTOR) pathway in vascular growth and organization which suggests a therapeutic target for patients with complicated vascular anomalies. The present protocol further supports this data. The overall goal of this trial is to objectively assess the efficacy of sirolimus compard to vincristine for the treatment of 50 patients with high risk KHE. A multi-center, Phase 2 trial with participation from 8 sites is proposed. The study will consist of two phases. The first of these is an initial induction phase in which vincristine and steroids will be compared to sirolimus and steroids. Response in the induction phase will be assessed as time to hematologic response. At the end of induction phase, cross-over can occur if there is failure to respond. Part 2 is a maintenance phase which will be 1 year in length. Continued safety and efficacy data will be collected, and there will be cross-over at any time for patients who lose their response. Formal response in maintenance will be evaluated by imaging studies, functional assessment, and quality of life as per study SIRDA- 0901. Failure at any time will be defined as worsening of hematologic parameters on two separate laboratory evaluations.

描述（由申请人提供）： 卡波西样血管内皮瘤 (KHE) 是极其罕见的危及生命的肿瘤，可能与卡萨巴赫-梅里特现象相关，包括严重的血小板减少症和低纤维蛋白原血症，导致显着的出血风险和高达 20% 至 30% 的相关死亡率。尽管潜在并发症很严重，但对于患有这些肿瘤的儿童和年轻人的治疗和治疗反应缺乏统一的指南。 KHE 患者接受了多种积极的药物治疗方案，但没有对疗效或安全性进行前瞻性评估。目前，长春新碱被认为是实践标准。其中一部分患者已接受研究 SIR-DA-0901 的治疗，这是一项评估西罗莫司治疗复杂血管异常的有效性和安全性的 2 期试验。尽管数量很少，但治疗的反应和耐受性似乎很有希望。临床前和临床数据支持磷酸肌醇 3 激酶/AKT/哺乳动物雷帕霉素靶蛋白 (PI3 激酶/AKT/mTOR) 通路在血管生长和组织中的重要调节功能，这为患有复杂性血管疾病的患者提供了一个治疗靶点。血管异常。本协议进一步支持该数据。本试验的总体目标是客观评估西罗莫司与长春新碱治疗 50 名高危 KHE 患者的疗效。提议进行一项由 8 个地点参与的多中心、第 2 阶段试验。该研究将分为两个阶段。第一个阶段是初始诱导阶段，其中将长春新碱和类固醇与西罗莫司进行比较 和类固醇。诱导阶段的反应将根据血液学反应的时间进行评估。在诱导阶段结束时，如果未能做出反应，可能会发生交叉。第 2 部分是维护阶段，为期 1 年。将持续收集安全性和有效性数据，对于失去反应的患者，将随时进行交叉。根据 SIRDA-0901 研究，将通过影像学研究、功能评估和生活质量来评估维持治疗的正式反应。任何时候的失败将被定义为两个单独的实验室评估中血液学参数恶化。