Clinical Trials of FTI Radiosensitization

FTI放射增敏的临床试验

• 批准号: 6949955
• 负责人: STEPHEN M HAHN
• 金额: $ 38.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949955
• 关键词: alkyltransferase; antineoplastics; biological signal transduction; biomarker; biopsy; clinical research; clinical trial phase I; clinical trial phase II; combination cancer therapy; dosage; drug screening /evaluation; enzyme inhibitors; epidermal growth factor; farnesyl compound; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplasm /cancer radiation therapy; nonsmall cell lung cancer; patient oriented research

DESCRIPTION (provided by applicant): Activation of the Ras signaling pathway has been associated with altered radiation sensitivity in vitro and in vivo. In human tumor cells in which the Ras signaling pathway is activated, inhibition of Ras farnesylation with farnesyltransferase inhibitors (FTI) leads to enhanced radiosensitivity. R115777 is a specific inhibitor of farnesyltransferase that has been studied extensively in the clinic. R115777 is an in vitro and in vivo radiosensitizer and inhibits the Ras signaling pathway. The long-term objective of this project is to develop R115777 in combination with radiotherapy as a targeted therapy for patients with non-small cell lung cancer (NSCLC). The specific aims of this grant are 1) to perform Phase I and Phase II clinical trials of the FTI, R115777 in combination with radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) and 2) to relate the status of molecular markers in NSCLC tumors to clinical efficacy of R115777 and radiotherapy. In the Phase I clinical study, the maximally tolerated dose (MTD) and recommended Phase II dose (RPTD) of R115777 in combination with standard radiotherapy will be determined. In the Phase II study, the efficacy of R115777 and standard radiotherapy will be determined in patients with locally advanced NSCLC. Specific molecular markers that are associated with activation of the Ras signaling pathway will be measured in NSCLC tumor biopsy specimens and will be related to the clinical efficacy of R115777 and radiotherapy.

描述（由申请人提供）：RAS信号通路的激活与体外和体内的辐射灵敏度的改变有关。在激活RAS信号通路的人类肿瘤细胞中，用Farneyltransferase抑制剂（FTI）抑制Ras Farneylation会导致增强的放射敏感性。 R115777是Farneylsylansferase的特定抑制剂，已在诊所进行了广泛的研究。 R115777是体外和体内放射增敏剂，并抑制RAS信号通路。该项目的长期目标是将R115777与放射疗法结合使用，作为非小细胞肺癌（NSCLC）患者的靶向治疗。该赠款的具体目的是1）在不可切除的非小细胞肺癌（NSCLC）和2）患者中，进行FTI，R115777的I期和II期临床试验与放射疗法结合使用，以将NSCLC肿瘤中分子标记的状态与R11577和Radiother的NSCLC肿瘤中的分子标记状态相关。在I期临床研究中，将确定R115777与标准放射疗法结合使用的最大耐受剂量（MTD）和建议的II期剂量（RPTD）。在II期研究中，将确定R115777和标准放射疗法的疗效在局部晚期NSCLC患者中。与RAS信号通路激活相关的特定分子标记将在NSCLC肿瘤活检标本中进行测量，并将与 R115777和放疗。