PHASE 1 EVALUATION OF INTRATUMORAL INTERLEUKIN-1 ALPHA

瘤内 INTERLEUKIN-1 ALPHA 的第一阶段评估

• 批准号: 3838227
• 负责人: J E JANIK
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838227
• 关键词: biopsy; clinical trials; dosage; drug administration routes; drug adverse effect; human subject; human therapy evaluation; human tissue; immunocytochemistry; interleukin 1; metastasis; neoplasm /cancer immunotherapy; vasculitis

The purpose of this protocol is to determine the maximum tolerated dose (MTD) of intralesional interleukin-I (IL-1) alpha. We plan to examine tumor specimens obtained before and after intralesional injection of IL-1 using immunohistochemical techniques. The tumor response in the injected lesion and in distant metastases will be monitored. A dose escalation scheme with half-log increments will be used to determine the MTD. The starting dose was 0.001 mu-g/kg; patients are currently being treated at the 0.1 mu-g/kg dose level. The MTD has not been determined to date. Patients treated with intralesional IL-1 alpha experienced similar toxicities to those observed with intravenous IL-1 alpha. Biopsy specimens of lesions injected with IL-1 show evidence of vasculitis with lymphoid aggregates surrounding vessels outside the injected tumor nodule and occasionally vessels within the tumor itself. Tumor biopsies have shown evidence of intratumoral lymphoid aggregates that were not identified on pretherapy biopsy specimens. Neither local nor systemic antitumor responses have occurred in this initial group of 15 patients.

本方案旨在确定最大耐受剂量 (MTD)白细胞介素-I（IL-1）α。 我们计划检查 在病灶内注射IL-1之前和之后获得的肿瘤标本 使用免疫组织化学技术。 注射的肿瘤反应 将监测病变和远处转移。 将使用半对数增量的剂量递增方案， 确定MTD。 起始剂量为0.001 μ g/kg; 目前以0.1 μ g/kg剂量水平治疗。 MTD没有 到目前为止已经确定。 接受病灶内IL-1 α治疗的患者 与静脉注射IL-1 α观察到的毒性相比。 活检 注射IL-1的病变标本显示血管炎的证据， 注射肿瘤结节外血管周围的淋巴聚集体 偶尔肿瘤内部也有血管 肿瘤活检有 显示了肿瘤内淋巴聚集的证据， 在治疗前活检标本上发现。 既不是局部的也不是系统的 抗肿瘤反应发生在15名患者的初始组中。