COMBRETASTATIN/DOXORUBICIN/CISPLATIN FOR PATIENTS WITH THYROID CANCER

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。这项由研究人员发起的研究是基于临床前数据和之前接受康铂A-4磷酸(CA4P)治疗的甲状腺癌患者的I期临床经验。这些研究的结果表明，CA4P适合在第二阶段的临床环境中进一步发展，作为间变性甲状腺癌综合治疗的一部分，有可能为这些患者确定一个新的护理标准。该研究的目的是：1)确定新诊断的地区性晚期甲状腺未分化癌基于CA4P的综合疗法(同时进行放疗和巩固治疗)的客观缓解率；2)确定基于CA4P的综合疗法是否通过将这些患者的中位生存期从10个月增加一倍至20个月而改变未分化甲状腺癌的自然病史；3)进一步描述作为综合疗法的一部分时CA4P的可耐受剂量和安全性；以及4)通过对包括药代动力学在内的几项指标的分析，确定基于CA4P的综合疗法的反应的临床预测因素。这项研究计划招收33名受试者(本网站最多27名受试者)。研究分为三个阶段：诱导阶段、联合模式阶段(随着CA4P剂量的增加)和巩固阶段。在诱导阶段，受试者将接受为期1个周期(3周)的初始联合化疗(阿霉素+顺铂+G-CSF(粒细胞集落刺激因子)或Neulasta)。在综合模式阶段，受试者将接受CA4P和放射治疗4周，然后用4-6周的时间恢复。在巩固阶段，CA4P将实施两个为期4周的周期。研究监测将包括生命体征、心电图和药代动力学采样。

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. This investigator-initiated study is based on preclinical data and previous Phase I clinical experience in patients with thyroid cancer who were treated with Combretastatin A-4 Phosphate (CA4P). Results from those studies suggest that CA4P is suitable for further clinical development in the Phase II setting as part of combined modality treatment for anaplastic thyroid cancer with the potential to define a new standard of care for these patients. The objectives of the study are: 1) to determine the objective response rate of CA4P-based combined modality therapy (with concurrent radiation and consolidation treatment) given to patients with newly diagnosed regionally advanced anaplastic carcinoma of the thyroid; 2) to determine whether CA4P-based combined modality therapy alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 months to 20 months; 3) to further characterize a tolerable dose and the safety profile of CA4P when administered as part of a combined modality regimen; and 4) to determine clinical predictors of response to CA4P-based combined modality therapy by analysis of several measures including pharmacokinetics. This study plans to enroll up to 33 subjects (with up to 27 subjects at this site). The study is separated into three phases: Induction Phase, Combined Modality Phase (with dose escalation of CA4P), and Consolidation Phase. During the Induction Phase, subjects will receive initial combination chemotherapy for 1 cycle (3 weeks) (doxorubicin + cisplatin + G-CSF (granulocyte-colony stimulating factor) or neulasta). In the Combined Modality Phase, subjects will receive CA4P and radiation therapy for 4 weeks and then spend 4-6 weeks recovering. In the Consolidation Phase, CA4P will be administered for two 4-week cycles. Study monitoring will include vital signs, EKGs and pharmacokinetic sampling.