GOG 203C: EVALUATION OF GLEEVEC IN TREATMENT OF CARCINOSARCOMA OF THE UTERUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。主要目标：1)通过6个月的无进展生存期来确定Gleevec TM的活性。2)根据不良事件通用术语标准，确定格列卫TM在该队列患者中出现不良反应的频率和严重程度。次要目标：#)确定无进展存活率的分布。4)估计客观应答率(部分和完全应答率(RECIST定义的部分和完全应答率)。5)确定影响预后的因素，如初始表现状态和组织学分级。探索性目的：6)确定在一线化疗前收集的存档的、福尔马林固定的、石蜡包埋的原发肿瘤中c-kit、PDGFR、AKT2和p-AKT2的表达水平。这是一项II期开放标签研究，评估了使用Gleevec TM治疗的子宫癌肉瘤患者的无进展存活率，这些患者在适当的局部治疗后有复发或持续性癌肉瘤的记录。所有患者必须至少在一个维度上有可测量的疾病。子宫肉瘤占所有接受治疗的子宫恶性肿瘤的2-6%。在一项对英国肿瘤登记的回顾中，癌肉瘤(CS)和平滑肌肉瘤(LMS)占15年来登记的所有子宫肉瘤的90%。本组患者总的五年生存率为31%。研究证实复发率为53%-56%，其中大部分包括额外的盆腔组件。虽然在这些研究中没有规定的术后治疗方案，但它们强调了缺乏有效的辅助治疗。如上所述，晚期和复发的子宫癌肉瘤总体上预后很差，绝大多数研究都未能证明辅助放射治疗或化疗可以改善总体存活率。因此，需要考虑和实施更多调查新型制剂的研究。这项研究建议评估格列卫TM在复发性或持续性子宫肌瘤中的作用

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary Objectives: 1) To determine the activity of Gleevec TM as measured by progression-free survival at six months. 2) To determine the frequency and severity of adverse effects of Gleevec TM in this cohort of patients as assessed by the Common Terminology Criteria of Adverse Events. Secondary Objectives: #) To determine the distribution of progression-free survival. 4) To estimate the objective response rate (partial and complete response rate (partial and complete response as defined under RECIST). 5) To determine effects of prognostic factors such as initial performance status and histological grade. Exploratory Objective: 6) To determine the levels of expression of c-KIT, PDGFR, AKT2, and p-AKT2 in archived, formalin-fixed, paraffin-embedded primary tumors collected prior to the initiation of first-line chemotherapy. This is a Phase II open-labeled study evaluating progression-free survival in patients treated with Gleevec TM who have recurrent or persistent carcinosarcoma of the uterus with documented disease progression after appropriate local therapy. All patients must have measurable disease in at least one dimension. Uterine sarcomas represent 2-6% of all uterine malignancies treated. In a review of British tumor registries, carcinosarcomas (CS) and leimyosarcomas (LMS) made up 90% of all uterine sarcomas registered over a 15-year period. The overall five year survival was 31% in this series. Studies have confirmed recurrence rates of 53-56%, the majority of which include an extra pelvic component. Although there was no prescribed postoperative therapy regimen in any of these studies, they highlight the lack of an efficacious adjuvant therapy. As discussed above, advanced and recurrent uterine carcinosarcomas carry a poor prognosis overall and the vast majority of studies have failed to demonstrate an improvement in overall survival with adjuvant radiation therapy or chemotherapy. As such, additional studies investigating novel agents need to be considered and implemented. This study proposes to evaluate Gleevec TM in the setting of recurrent or persistent uterine sarco