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（Kaposiform hemangiovendotheliomas，KHE）是一种非常罕见的危及生命的肿瘤，它可能与Kasabach-Merritt现象有关，包括严重的血小板减少和低纤维蛋白原血症，导致显著的出血风险和高达20%至30%的相关死亡率。尽管潜在并发症的严重性，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导方针。KHE患者已经接受了多种积极的药物治疗方案，但没有对反应或安全性进行前瞻性评价。目前，长春新碱被认为是实践标准。这些患者的一个亚组已在研究SIR-DA-0901中接受治疗，这是一项评估西罗莫司治疗复杂性血管异常的疗效和安全性的II期试验。虽然数量很少，但对治疗的反应和耐受性似乎很有希望。有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（PI 3激酶/AKT/mTOR）通路在血管生长和组织中的基本调节功能，这表明了复杂血管异常患者的治疗靶点。本方案进一步支持该数据。本试验的总体目标是客观评估西罗莫司与长春新碱相比治疗50例高危KHE患者的疗效。拟定了一项由8家临床试验机构参与的多中心II期试验。研究将分两个阶段进行。第一个阶段是初始诱导阶段，将长春新碱和类固醇与西罗莫司进行比较 和类固醇诱导期的缓解将评估为至血液学缓解的时间。在诱导阶段结束时，如果没有反应，可能会发生交叉。第2部分是维护阶段，为期1年。将收集持续的安全性和疗效数据，对于失去应答的患者，将在任何时间进行交叉。根据研究SIRDA- 0901，将通过影像学研究、功能评估和生活质量评价维持期的正式缓解。任何时间的失败定义为两次单独实验室评价中血液学参数恶化。