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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是确定不同程度肝功能障碍患者组中帕唑帕尼的MTD和DLT，以便为此类患者提供帕唑帕尼的适当给药建议，表征帕唑帕尼和代谢物的PK和PD特征，记录非DLT;探索肝功能障碍的Child-Pugh分级与帕唑帕尼给药的观察到的毒性、血浆PK和PD的相关性，并记录与帕唑帕尼治疗相关的任何抗肿瘤活性。 该试验预计将以每月约5例患者的速度招募患者，总计招募72-132例患者。 帕唑帕尼是VEGFR-1、VEGFR-2、VEGFR-3、PDGFR-<$、PDGFR-<$和c-kit的强效、多靶向受体酪氨酸激酶抑制剂，在肾细胞癌中显示出活性，伴肿瘤缩小和病情稳定。 目前，帕唑帕尼单药治疗和与拉帕替尼联合治疗肝癌、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、卵巢癌和各种类型肉瘤患者的I、II和III期试验正在进行或计划进行。

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.