COMBRETASTATIN A-4 PHOSPHATE IN ADVANCED ANAPLASTIC THYROID CARCINOMA

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。CA4P是一种新型抗癌药物，对肿瘤血管具有较强的选择性毒性。除了在啮齿动物肿瘤模型中作为单一药物的活性外，CA4P还被证明可以增强或与几种化疗药物和放射治疗协同作用。CA4P在三个I期试验中进行了评估。本试验的目的是确定客观有效率，确定有效的临床预测因素，并进一步确定CA4P治疗甲状腺未分化癌患者的安全性。这项研究还试图确定CA4P是否通过将晚期疾病患者的中位生存期从4-6个月增加到12个月而改变间变性甲状腺癌的自然病史。为了满足29名受试者的样本规模，这项研究将在三个地点招募多达36名受试者。CA4P剂量为45 mg/m2，每周静脉滴注10分钟，连续3周，然后休息1周(1周期=4周)。受试者将在门诊基础上来GCRC进行用药和EKG(在周期2之后，EKG监测可能减少；在周期6之后，EKG监测可能停止)。药代动力学采样将仅在第1周期进行。周期可能持续到疾病进展，或在记录到完全缓解后持续两个周期。

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. CA4P is a novel anti-cancer agent that displays potent and selective toxicity towards tumor vasculature. Aside from its activity as a single agent in rodent tumor models, CA4P has been shown to enhance or act synergistically with several chemotherapy agents and radiation. CA4P was evaluated in three Phase I trials. The objectives of this trial are to determine the objective response rate, to determine the clinical predictors of response, and to further characterize the safety profile of CA4P given to patients with anaplastic carcinoma of the thyroid. The study also attempts to determine whether CA4P alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of patients with advanced disease from 4-6 months to 12 months. To meet the sample size of 29 subjects, the study will enroll up to 36 subjects at three sites. Patients will receive CA4P at a dose of 45 mg/m2 as a 10-minute intravenous infusion weekly for 3 weeks followed by one week of rest (1 Cycle = 4 weeks). Subjects will come to the GCRC on an outpatient basis for medication administration and EKGs (after Cycle 2, EKG monitoring may be reduced; after Cycle 6, EKG monitoring may be halted). Pharmacokinetic sampling will be done only during Cycle 1. Cycles may continue until disease progression or for two cycles beyond documentation of complete remission.