确认：一项双盲、安慰剂对照的III期临床试验，研究纳武单抗对复发间皮瘤患者的疗效：一项随机对照试验的研究方案
CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.
作者信息
Fennell Dean A, Kirkpatrick Emma, Cozens Kelly, Nye Mavis, Lester Jason, Hanna Gerard, Steele Nicola, Szlosarek Peter, Danson Sarah, Lord Joanne, Ottensmeier Christian, Barnes Daniel, Hill Stephanie, Kalevras Mihalis, Maishman Tom, Griffiths Gareth
机构信息
University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK.
Southampton Clinical Trials Unit, Centre for Cancer Immunology, University of Southampton, Southampton, UK.
出版信息
Trials. 2018 Apr 18;19(1):233. doi: 10.1186/s13063-018-2602-y.
BACKGROUND
Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
METHODS
The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).
DISCUSSION
The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.
TRIAL REGISTRATION
EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.
背景
间皮瘤是一种无法治愈、抗凋亡的癌症，大多数情况下由既往接触石棉所致，且发病率呈上升趋势。它构成了日益加重的健康负担，但研究仍不充分，治疗选择有限。间皮瘤中与PD-L1和PD-1靶向治疗相关的早期有前景的活性信号表明间皮瘤依赖于这种免疫检查点。有必要在复发间皮瘤患者中评估检查点抑制剂，这类患者的治疗选择有限。
方法
在英国将进行一项随机、安慰剂对照的III期试验（英国癌症研究中心CONFIRM试验），在标准治疗基础上加用12个月的纳武单抗（抗PD1抗体）。将从英国二级医疗机构招募总共336例接受过至少两线先前治疗的胸膜或腹膜间皮瘤患者。患者将按2:1随机分组（纳武单抗：安慰剂），根据上皮样/非上皮样进行分层，接受240mg纳武单抗单药治疗或生理盐水安慰剂，静脉输注30分钟。治疗时间最长为12个月。我们将确定使用纳武单抗是否能提高总生存期（主要疗效终点）。次要终点将包括无进展生存期、客观缓解率、毒性、生活质量和成本效益。将根据意向性分析原则，对主要终点（以及其他事件发生时间终点）使用Cox回归分析进行分析。
讨论
该试验结果将为使用纳武单抗治疗复发间皮瘤的潜在益处提供证据。如果被证明在临床有效、安全且具有成本效益，它可能会成为英国新的治疗标准。
试验注册
欧洲药品管理局临床试验编号：2016-003111-35（于2016年7月21日录入）；ClinicalTrials.gov标识符：NCT03063450。于2017年2月24日注册。
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