COMBRETASTATIN A-4 PHOSPHATE IN ADVANCED ANAPLASTIC THYROID CARCINOMA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。CA4P是一种新型抗癌药物，对肿瘤血管具有强效和选择性的毒性。除了在啮齿动物肿瘤模型中作为单一药物的活性外，CA4P已被证明可以增强或与几种化疗药物和放疗协同作用。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反应率，确定反应的临床预测因素，并进一步确定给予甲状腺间变性癌患者CA4P的安全性。该研究还试图确定CA4P是否通过将晚期患者的中位生存期从4-6个月增加一倍至12个月来改变间变性甲状腺癌的自然史。为了满足29名受试者的样本量，该研究将在三个地点招募多达36名受试者。患者将接受45 mg/m2剂量的CA4P，每周静脉输注10分钟，持续3周，然后休息1周（1周期= 4周）。受试者将在门诊基础上到GCRC进行药物管理和心电图检查（第2周期后，心电图监测可能减少；第6周期后，心电图监测可能停止）。药代动力学取样将只在第1周期进行。周期可以持续到疾病进展或超过完全缓解的两个周期。

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.