A PHASE I EVALUATION OF THE SAFETY AND PK OF PRO-1 IN STAGE IV MELANOMA PATIENTS

PRO-1 在 IV 期黑色素瘤患者中的安全性和 PK 的 I 期评估

• 批准号: 7379363
• 负责人: JOHN A THOMPSON
• 金额: $ 0.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379363
• 关键词: PHASE; EVALUATION; SAFETY; PK; PRO

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 study evaluates a new DNA delivery technology designed to deliver genes to sites of tumor growth, resulting in tumor-selective expression of the delivered gene. This technology, called SPLP (stable plasmid-lipid particles), allows the intravenous delivery of genes that encode therapeutic proteins. SPLP are specialized liposomes in which a single plasmid DNA is encapsulated inside a lipid bi-layer. SPLP have a long circulation lifetime in the blood. Tumor accumulation of SPLP takes place passively over the long circulation time. The fact that the blood vessels in growing tumors are leaky allows the SPLP to reach the tumor cells. This study evaluates the safety and pharmacokinetics of the intravenous delivery of Pro-1 to Stage IV metastatic melanoma subjects, followed by treatment with Valtrex. Pro-1 and Valtrex work together to kill tumor cells. The primary objectives are to evaluate the safety of escalating doses of Pro-1 and to measure the pharmacokinetics of Pro-1 clearance from the blood of treated subjects. Secondary objectives are to evaluate the presence of thymidine kinase plasmid DNA in tumor tissue in subjects with appropriate skin lesions and to evaluate the clinical side effects of Pro-1 treatment followed by Valtrex administration on treated subjects' disease.

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。本研究评估了一种新的DNA传递技术，该技术旨在将基因传递到肿瘤生长部位，从而导致所传递基因的肿瘤选择性表达。这项技术被称为SPLP（稳定质粒脂质颗粒），它允许静脉输送编码治疗蛋白的基因。SPLP是一种特殊的脂质体，其中单个质粒DNA被包裹在脂质双层内。SPLP在血液中有很长的循环寿命。肿瘤中SPLP的积累是在长循环时间内被动发生的。生长肿瘤中的血管是渗漏的这一事实使得SPLP能够到达肿瘤细胞。本研究评估了IV期转移性黑色素瘤患者静脉注射Pro-1的安全性和药代动力学，随后使用Valtrex治疗。Pro-1和Valtrex共同作用杀死肿瘤细胞。主要目的是评估不断增加的Pro-1剂量的安全性，并测量治疗对象血液中Pro-1清除的药代动力学。次要目的是评估胸苷激酶质粒DNA在患有适当皮肤病变的受试者肿瘤组织中的存在，并评估Pro-1治疗后给予Valtrex对治疗对象疾病的临床副作用。