Cambridge University Hospitals National Health Service Foundation Trust, Hill's Road, Cambridge, UK.
Southampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
BMC Cancer. 2022 Sep 1;22(1):946. doi: 10.1186/s12885-022-09891-9.
For patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis. For these patients, standard care chemotherapy only offers them survival of less than a year. Nivolumab, a checkpoint blockade inhibitor, has been found to work in some advanced cancers. It is proposed, for those where immunotherapy hasn't worked, that these immunologically evasive tumours need to be sensitized to immunotherapy drugs to allow them to act.
ELEVATE is a single arm phase II trial testing the overall response to nivolumab following temozolomide treatment in patients with advanced unresectable previously treated adenocarcinoma which is O-methylguanine-DNA-methyltransferase (MGMT) methylated. 18 patients are being recruited from UK secondary care sites. To be eligible, participants must have been treated with at least 3 months of platinum and fluoropyrimidine chemotherapy. Participants will receive 50 mg/m temozolomide continuously for 3 months. If their disease progresses during the 3 months, they will stop temozolomide and start nivolumab at a dose of 240mg every 2 weeks. If there is no progression after 3 months the participant will continue taking temozolomide in combination with nivolumab. All treatment will stop once the participant progresses on nivolumab. The primary endpoint is the best overall response to nivolumab, using both Response Evaluation Criteria in Solid Tumours version 1.1 and immunotherapy modified Response Evaluation Criteria in Solid Tumours. Secondary endpoints include progression-free survival, overall survival, and quality of life.
ELEVATE will provide evidence for whether giving nivolumab after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma is safe and biologically effective prior to future randomised trials.
EudraCT Number: 2020-004771-41 (issued 01 October 2020); ISCRTN11398887 (registered 14 July 2021).
对于患有食管胃腺癌的患者，手术是唯一的治愈方法，尽管采用了包括化疗和/或放疗的多模式治疗，但仍有超过 50%的患者会复发和死亡。许多英国患者在诊断时已经患有晚期疾病，或者已经无法手术或转移。对于这些患者，标准护理化疗只能提供不到一年的生存时间。纳武单抗（nivolumab），一种检查点抑制剂，已被发现对一些晚期癌症有效。有人提出，对于那些免疫治疗无效的患者，这些免疫逃避肿瘤需要被敏化以使其能够对免疫治疗药物产生反应。
ELEVATE 是一项单臂 II 期试验，旨在测试替莫唑胺治疗后纳武单抗在先前接受过治疗的不可切除的晚期腺性癌中的总体反应，这些患者的 O-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）甲基化。该试验正在英国二级医疗机构招募 18 名患者。入选标准为：至少接受过 3 个月的铂类和氟嘧啶化疗。参与者将连续 3 个月接受 50mg/m 的替莫唑胺治疗。如果在 3 个月内疾病进展，他们将停止替莫唑胺并开始使用 240mg 纳武单抗每 2 周一次。如果 3 个月后没有进展，参与者将继续服用替莫唑胺联合纳武单抗。一旦患者在纳武单抗治疗中进展，所有治疗都将停止。主要终点是使用实体瘤反应评估标准 1.1 版和免疫治疗改良实体瘤反应评估标准评估纳武单抗的最佳总体反应。次要终点包括无进展生存期、总生存期和生活质量。
ELEVATE 将提供证据，证明在先前接受过治疗的晚期食管胃腺癌患者中，替莫唑胺后给予纳武单抗是否安全且具有生物学疗效，为未来的随机试验做准备。
EudraCT 编号：2020-004771-41（2020 年 10 月 1 日发布）；ISCRTN11398887（2021 年 7 月 14 日注册）。
