Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial.
Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial.
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DOI：
10.1186/s13063-015-1101-7
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发表时间：
2015-12-16
期刊：
影响因子：
2.5
通讯作者：
Harbeck N
中科院分区：
文献类型：
--
作者：
Yardley DA;Brufsky A;Coleman RE;Conte PF;Cortes J;Glück S;Nabholtz JM;O'Shaughnessy J;Beck RM;Ko A;Renschler MF;Barton D;Harbeck N
三阴性乳腺癌是一种侵袭性疾病，临床需求未得到满足。在一项针对转移性三阴性乳腺癌患者的 III 期研究中，一线吉西他滨/卡铂的中位无进展生存期为 4.6 个月。基于白蛋白结合型紫杉醇的治疗方案（使用吉西他滨或卡铂±贝伐珠单抗）也在人表皮生长因子受体 2 阴性转移性乳腺癌的一线 II 期试验中证明了有效性和安全性。在这项国际、多中心、开放标签、随机 II/III 期试验中，将一线白蛋白结合型紫杉醇联合吉西他滨或卡铂与吉西他滨/卡铂（对照组）治疗转移性三阴性乳腺癌的疗效和安全性进行比较。在 II 期部分，240 名患有可测量的转移性三阴性乳腺癌且未接受过转移性疾病治疗的患者将按 1:1:1（按无病间隔分层：≤ 1 与 > 1 年）随机分配至白蛋白结合型紫杉醇 125 mg/m2 加吉西他滨 1000 mg/m2、白蛋白结合型紫杉醇 125 mg/m2 加卡铂曲线下面积 2 mg × min/mL，或吉西他滨 1000 mg/m2 加卡铂曲线下面积 2 mg × min/mL，均在 21 天周期的第 1 天和第 8 天给药。将评估研究者评估的无进展生存期（主要终点）、总体缓解率、总体生存率和安全性。将使用五个功效和安全性参数的排名算法来选出白蛋白结合型紫杉醇疗法的“获胜者”。在 III 期部分，550 名患者将按 1:1 的比例随机分配至从 II 期部分选择的白蛋白结合型紫杉醇联合组或对照组（按无病间隔：≤ 1 与 >1 年分层，以及既往使用辅助/新辅助紫杉烷）。 II 期患者将不属于 III 期人群。 III 期主要终点是盲法、独立评估的无进展生存期；次要终点包括盲法、独立评估的总体缓解率、总体生存率、疾病控制率、缓解持续时间和安全性。还将进行生物标志物和循环肿瘤细胞探索性分析以及生活质量评估。附加文件 1 中提供了批准伦理机构的名单。tnAcity 试验旨在确定一种新的标准细胞毒性化疗方案，用于转移性三阴性乳腺癌的一线治疗。 ClinicalTrials.gov：NCT01881230。注册日期：2013 年 6 月 17 日。本文的在线版本 (doi:10.1186/s13063-015-1101-7) 包含补充材料，可供授权用户使用。
Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin ± bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer. In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer. In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤ 1 versus > 1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg × min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg × min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the “winner” of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤ 1 versus > 1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently-assessed overall response rate, overall survival, disease control rate, duration of response, and safety. Biomarker and circulating tumor-cell exploratory analyses and quality-of-life assessments will also be performed. A list of approving ethical bodies was provided in Additional file 1. The tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer. ClinicalTrials.gov: NCT01881230. Date of registration: 17 June 2013. The online version of this article (doi:10.1186/s13063-015-1101-7) contains supplementary material, which is available to authorized users.