SBRT+PD-1单抗对比单纯SBRT治疗广泛转移腺样囊性癌前瞻性研究计划书

A radomized study of SBRT with or without PD-1 in patients with metastatic adenoid cystic carcinoma:study protocol for randomized trail

背景与目的广泛转移的腺样囊性癌(ACC)应用常规疗法(常规放疗、化疗或手术)疗效不佳,指南推荐首选参加临床试验。随着免疫治疗和立体定向放疗(SBRT)两项“非常规”治疗手段的应用日渐成熟以及远隔效应的发现,为这类患者带来了新的希望。本研究拟采用开放标签的前瞻性随机对照研究来探索SBRT联合PD-1单抗对比单纯SBRT治疗对于广泛转移的ACC患者的疗效和远隔效应诱发概率,并验证这种全新的治疗模式应用在广泛期ACC治疗的安全性和有效性。方法与分析本研究为验证SBRT联合PD-1单抗及单用SBRT两种疗法的有效性与安全性,设计了一项开放标签、多中心、前瞻性随机对照研究。主要研究终点为1年治疗总有效率,次要终点为总生存率、无进展生存率等,将按意向性治疗人群作为统计材料通过Kaplan-Meier生存分析评价以上指标。次要终点生活质量将应用单侧Wilcoxon秩检验比较FACT-G评分结果。伦理与发布本项研究将于近期提交北京医院伦理委员会进行审查。有关临床数据将发布在相关专业杂志期刊中。临床试验注册本研究拟于近期在ClinicalTrails.gov平台注册。

Background and purpose Conventional therapy(conventional radiotherapy,chemotherapy or surgery)is not effective for patients with extensive metastasis of adenoid cystic carcinoma(ACC).Current guidelines recommend them to participate in clinical trials first.With the application of immunotherapy(PD-1)and stereotactic body radiation therapy(SBRT),two"unconventional"therapies,and the discovery of abscopal effect,bring new hope to these patients.We propose an open label prospective randomized trial to explore the efficacy of SBRT combined with PD with SBRT alone in patients with extensive metastasis of ACC,and to verify the safety and effectiveness of this new treatment mode in the treatment of extensive ACC.Methods and analysis To test the efficacy and safety,a randomised,open-label,multicenter trial was designed to evaluate the effect of SBRT with or without PD-1 inhibitor to treated the extensive ACC,with 1 year over all response rate as the primary endpoint.Secondary endpoints included progression-free survival quality of life and overall survival.All analyses were intention-to-treat.The survival curves will be constructed as time-to event plots using the Kaplan-Meier method.QOL was measured using FACT-G scores,with differences between groups tested with Wilcoron rank test.Ethics and dissemination This study will be approved by the Beijing Hospital Ethics Committee.The results wil be submitted for publication in peer-reviewed journals.Trail registration This study will be carried out in the near future ClinicalTrails.gov to register.