PHASE II TRIAL OF IL-1 ALPHA + INDOMETHACIN IN MELANOMA PATIENTS

IL-1 α吲哚美辛在黑色素瘤患者中的 II 期试验

• 批准号: 3838231
• 负责人: J W SMITH
• 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/3838231
• 关键词: biological response modifiers; clinical trials; combination chemotherapy; dosage; etoposide; human subject; human therapy evaluation; human tissue; immunomodulators; indomethacin; interleukin 1; melanoma; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer remission /regression

IL-1alpha has antiproliferative activity against human melanoma cell lines, causes murine melanoma tumors to shrink in vivo, can induce interferons and interleukin-2 which have activity in melanoma, and can enhance the activity of cytotoxic T cells and other effector cells. Animal studies suggested that indomethacin increased the antitumor effects of IL-1. For these reasons, we designed this phase II study in melanoma patients to determine the anti-tumor activity of IL-1alpha plus indomethacin using the maximum tolerated dose of IL-1alpha from our earlier phase I trial. A total of 49 patients have entered the study, and all are evaluable for response. None of the 14 patients with predominately visceral metastases responded to treatment. Of the 35 patients with non-visceral metastases, four patients responded (1 CR, 3 PR) for a response rate of 11% (95% confidence interval: 5-26%). These results indicate that IL-1alpha has a low level of activity in melanoma. In an effort to enhance this activity, we amended this trial to combine etoposide (VP-16) with this regimen based on preclinical studies that demonstrated synergistic antitumor effects with the combination. Of the 13 patients enrolled to date, 11 are evaluable and none have responded.

IL-1Alpha具有针对人黑色素瘤细胞的抗增生活性 线，导致鼠类黑色素瘤肿瘤在体内收缩，可能诱导 干扰素和白介素-2在黑色素瘤中具有活性，可以 增强细胞毒性T细胞和其他效应细胞的活性。 动物研究表明，吲哚美辛增加了抗肿瘤 IL-1的影响。 由于这些原因，我们在 黑色素瘤患者确定IL-1Alpha Plus的抗肿瘤活性 使用我们的最大耐受剂量的IL-1Alpha吲哚美辛 较早的第一阶段试验。 总共49名患者进入了研究， 所有这些都是可以评估的。 14例患者中没有 主要的内脏转移对治疗做出了反应。 35 非野主转移的患者，四名患者反应（1 CR，3例 PR）的响应率为11％（95％置信区间：5-26％）。 这些 结果表明，IL-1Alpha在黑色素瘤中的活性水平较低。 为了增强这项活动，我们修改了该试验以结合 基于临床前研究的依托泊苷（VP-16）与该方案 与该组合相结合表现出协同的抗肿瘤作用。 的 迄今为止，有13名患者可以评估11例，没有任何反应。