CLINICAL TRIAL: PHASE 1 AND PHARMACOKINETIC SINGLE AGENT STUDY OF PAZOPANIB ADVA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是在不同程度的肝功能障碍患者中建立帕佐帕尼的MTD和DLT，以便为此类患者提供合适的帕佐帕尼剂量建议，描述帕佐帕尼及其代谢物的PK和PD谱，记录非DLTS；探讨Child-Pugh肝功能障碍分类与观察到的毒性、血浆PK和PD的相关性，以及记录与帕佐帕尼治疗相关的任何抗肿瘤活性。 这项试验预计将以每月约5名患者的速度增加患者，总计72-132名患者。 帕佐帕尼是一种有效的、多靶点的VEGFR-1、VEGFR-2、VEGFR-3、PDGFR-β、PDGFR-β和c-KIT受体酪氨酸激酶抑制剂，已在肿瘤缩小和病情稳定的肾癌中显示出活性。目前帕佐帕尼作为单一疗法以及与拉帕替尼联合治疗的I、II和III期试验正在进行中或计划用于肝癌、转移性肾细胞癌、恶性胶质瘤、非小细胞肺癌、晚期乳腺癌、多发性骨髓瘤、卵巢癌和各种类型的肉瘤患者。

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. Objectives of this study are to establish the MTD and DLT of pazopanib in groups of patients with varying degrees of hepatic dysfunction in order to provide appropriate dosing recommendations for pazopanib in such patients, to characterize the PK and PD profiles of pazopanib and metabolites, to document the non-DLTs; to explore correlations of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma PK, and PD of pazopanib administration, and to document any antitumor activity associated with pazopanib treatment. The trial is expected to accrue patients at a rate of approximately 5 patients per month for a total accrual of 72-132 patients. Pazopanib is a potent, multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-¿, PDGFR-¿, and c-kit and has shown activity in renal cell cancer with tumor shrinkage and stable disease. Current phase I, II, and III trials of pazopanib as single therapy and in combination with lapatinib are ongoing or planned for patients with liver cancer, metastatic renal cell carcinoma, malignant glioma, non-small cell lung cancer, advanced breast cancer, multiple myeloma, ovarian cancer, and various types of sarcomas.