Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC Phase 3 Randomized Controlled Trial.
Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC Phase 3 Randomized Controlled Trial.
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DOI：
10.2196/11234
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发表时间：
2018-08-15
影响因子：
1.7
通讯作者：
Salem R
中科院分区：
文献类型：
--
作者：
Chauhan N;Bukovcan J;Boucher E;Cosgrove D;Edeline J;Hamilton B;Kulik L;Master F;Salem R
在全球范围内，肝细胞癌是癌症死亡的第二大常见原因。加强癌症治疗而不损害肝功能仍然具有挑战性。TheraSphere治疗不可切除的肝细胞癌（STOP-HCC）研究的目的是检查经动脉放射性栓塞（TheraSphere钇-90玻璃微球）联合索拉非尼标准一线治疗将改善不可切除的肝细胞癌患者的结局的假设。STOP-HCC研究是动脉内治疗联合索拉非尼治疗不可切除肝细胞癌的最大国际、多中心、前瞻性研究。在这里，我们报告研究设计。STOP-HCC是一项前瞻性、III期、开放标签、随机对照研究，在北美、欧洲和亚洲多达105个研究中心进行。符合条件的成人患有不可切除的肝细胞癌，预期寿命至少为12周，有1个或多个一维可测量病灶，Child-Pugh评分≤ 7分，东部肿瘤协作组体能状态评分≤ 1分，并且是索拉非尼治疗的候选人。允许存在分支门静脉肿瘤血栓形成。患者以1：1的比例随机分配接受索拉非尼单药治疗或经动脉放射性栓塞治疗，随后在2至6周内接受索拉非尼治疗。主要结局是总生存期。次要结局是至进展时间、至无法治疗的进展时间、至症状进展时间、肿瘤缓解、生活质量和不良事件发生。该研究是一项适应性试验，包括一项组序贯设计，其中包括2项中期分析（520例患者），并可选择在第二次中期分析时将样本量增加至700例患者。520例患者的样本量允许417例死亡，提供80%的把握度来检测中位总生存期从索拉非尼组的10.7个月（基于索拉非尼肝细胞癌评估随机方案[SHARP]试验）增加到经动脉放射栓塞+索拉非尼组的14.2个月（风险比0.754），双侧α为0.05。样本量增加至700例患者，允许564例死亡，以提供80%的把握度来检测中位总生存期的较小差异，从索拉非尼组的10.7个月到经动脉放射性栓塞+索拉非尼组的13.7个月（风险比0.781）。研究入组于2017年9月完成。第一次和第二次中期分析的结果由独立数据监查委员会审查。在两次中期分析中，委员会的建议是继续研究，不作任何变更。STOP-HCC研究将有助于确立经动脉放射性栓塞和索拉非尼联合治疗在治疗不可切除的肝细胞癌伴或不伴分支门静脉肿瘤血栓形成中的作用。ClinicalTrials.gov NCT 01556490; https://clinicaltrials.gov/ct2/show/NCT01556490（由WebCite存档，网址为http：//www.webcitation.org/7188iygKs）。RR1-10.2196/11234
Globally, hepatocellular carcinoma is the second most common cause of cancer deaths. It remains challenging to intensify cancer treatment without impairing liver function. The objective of the TheraSphere in the Treatment of Patients with Unresectable Hepatocellular Carcinoma (STOP-HCC) study is to examine the hypothesis that transarterial radioembolization (TheraSphere yttrium-90 glass microspheres) combined with standard first-line treatment with sorafenib will improve outcomes over treatment with sorafenib alone in unresectable hepatocellular carcinoma. The STOP-HCC study is the largest international, multicenter, prospective study of intra-arterial treatment in combination with sorafenib in unresectable hepatocellular carcinoma. Here we report the study design. STOP-HCC is a prospective, phase 3, open-label, randomized controlled study conducted across up to 105 sites in North America, Europe, and Asia. Eligible adults have unresectable hepatocellular carcinoma and a life expectancy of at least 12 weeks, 1 or more unidimensional measurable lesions, Child-Pugh score 7 points or less, and Eastern Cooperative Oncology Group Performance Status score 1 or lower, and are candidates for treatment with sorafenib. Presence of branch portal vein tumor thrombosis is permitted. Patients were randomly assigned in a 1:1 ratio to receive either sorafenib alone or transarterial radioembolization followed by sorafenib within 2 to 6 weeks. The primary outcome is overall survival. Secondary outcomes are time to progression, time to untreatable progression, time to symptomatic progression, tumor response, quality of life, and adverse event occurrence. The study is an adaptive trial, comprising a group-sequential design with 2 interim analyses with 520 patients, and an option to increase the sample size to 700 patients at the second interim analysis. The sample size of 520 patients allows for 417 deaths to give 80% power to detect an increase in median overall survival from 10.7 months for the sorafenib group (based on the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol [SHARP] trial) to 14.2 months for the transarterial radioembolization+sorafenib group (hazard ratio 0.754) with 2-sided alpha of .05. The increased sample size of 700 patients allows for 564 deaths to give 80% power to detect a smaller difference in median overall survival from 10.7 months for the sorafenib group to 13.7 months for the transarterial radioembolization+sorafenib group (hazard ratio 0.781). Enrollment for the study completed in September 2017. Results of the first and second interim analyses were reviewed by the Independent Data Monitoring Committee. The recommendation of the committee, at both interim analyses, was to continue the study without any changes. The STOP-HCC study will contribute toward the establishment of the role of combination therapy with transarterial radioembolization and sorafenib in the treatment of unresectable hepatocellular carcinoma with and without branch portal vein tumor thrombosis. ClinicalTrials.gov NCT01556490; https://clinicaltrials.gov/ct2/show/NCT01556490 (Archived by WebCite at http://www.webcitation.org/7188iygKs). RR1-10.2196/11234