Makimoto Atsushi, Matsui Motohiro, Chin Motoaki, Koh Katsuyoshi, Tomotsune Masako, Kaneko Tetsuji, Morikawa Yoshihiko, Yuza Yuki
Department of Hematology / Oncology, Tokyo Metropolitan Children's Medical Center, 2-8-29, Musashidai, Fuchu-shi, Tokyo, 183-8561, Japan.
Clinical Trial Support Center, Tokyo Metropolitan Children's Medical Center, 2-8-29, Musashidai, Fuchu-shi, Tokyo, 183-8561, Japan.
Contemp Clin Trials Commun. 2019 Aug 22;16:100440. doi: 10.1016/j.conctc.2019.100440. eCollection 2019 Dec.
Although cisplatin is one of the most effective agents against various pediatric cancers, it is sometimes difficult to manage due to its dose-limiting nephrotoxicity. Magnesium sulfate (Mg) showed a kidney-protective effect against cisplatin-induced nephrotoxicity (CIN) by regulating renal platinum accumulation both in vitro and in vivo, and the body of clinical data demonstrating the efficacy of this drug in adult cancer patients is increasing.In this open, multicenter, phase-2, randomized trial, patients under age 18 years who are scheduled to receive cisplatin-containing chemotherapy will be enrolled and randomly allocated either to an Mg supplementation arm in even-numbered chemotherapy courses (arm AB) or to another arm in odd-numbered courses (arm BA), with a 1:1 allocation. Analysis objects will be reconstructed into two groups depending on whether the chemotherapy course has Mg supplementation (group B) or not (group A). The primary endpoint is the proportion of chemotherapy courses resulting in elevated serum creatinine equal to or greater than 50% of the prechemotherapy value. For the secondary endpoints, various parameters for measuring kidney function, such as serum cystatin-C, B2M, L-FABP, NGAL, and urinary NAG in the two groups will be compared. A sample size based on alpha = 5% and 80% power requires at least 40 samples per group (ideally, 60 samples per group).If Mg demonstrates efficacy, a phase-3 study to confirm the prophylactic effect of Mg supplementation in both acute and chronic CIN will be developed using novel and better biomarkers.
UMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.
尽管顺铂是治疗多种儿童癌症最有效的药物之一，但由于其剂量限制性肾毒性，有时难以管理。硫酸镁（Mg）通过在体外和体内调节肾脏铂积累，对顺铂诱导的肾毒性（CIN）显示出肾脏保护作用，并且证明该药物对成年癌症患者有效的临床数据正在增加。
在这项开放、多中心、2期随机试验中，计划接受含顺铂化疗的18岁以下患者将被纳入，并随机分配到偶数化疗疗程的Mg补充组（AB组）或奇数疗程的另一组（BA组），分配比例为1:1。分析对象将根据化疗疗程是否有Mg补充分为两组（B组）或无Mg补充组（A组）。主要终点是导致血清肌酐升高至化疗前值的50%或更高的化疗疗程比例。对于次要终点，将比较两组中测量肾功能的各种参数，如血清胱抑素-C、B2M、L-FABP、NGAL和尿NAG。基于α=5%和80%检验效能的样本量要求每组至少40个样本（理想情况下，每组60个样本）。
如果Mg显示出疗效，将使用新的和更好的生物标志物开展3期研究，以确认Mg补充在急性和慢性CIN中的预防作用。
UMIN-CTR（http://www.umin.ac.jp/icdr/index.html）标识符UMIN000029215。
