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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。这项研究评估了一种新的DNA递送技术，旨在将基因传递到肿瘤生长部位，从而导致肿瘤选择性基因的表达。该技术称为SPLP（稳定的质粒脂质颗粒），允许静脉注射编码治疗蛋白的基因。 SPLP是专门的脂质体，其中将单个质粒DNA封装在脂质双层内。 SPLP的血液循环寿命很长。 SPLP的肿瘤积累发生在长时间的循环时间内。生长肿瘤中的血管泄漏的事实使SPLP可以到达肿瘤细胞。这项研究评估了Pro-1静脉注射到IV期转移性黑色素瘤受试者的安全性和药代动力学，然后对Valtrex进行治疗。 Pro-1和Valtrex一起杀死肿瘤细胞。主要目的是评估Pro-1剂量升级的安全性，并从治疗受试者的血液中测量Pro-1清除的药代动力学。次要目的是评估具有适当皮肤病变的受试者中胸苷激酶质粒DNA在肿瘤组织中的存在，并评估Pro-1治疗的临床副作用，然后对治疗受试者疾病进行valtrex给药的临床副作用。