双甘油抗坏血酸酯（阿米托斯DGA）预防接受舒尼替尼治疗的肾细胞癌患者手足皮肤反应的安全性和有效性：一项I/II期、非对照、单臂、开放标签试验方案

Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial.

作者信息

Yamamoto Kazuhiro, Ioroi Takeshi, Harada Kenichi, Nishiyama Satoshi, Nishigori Chikako, Yano Ikuko

机构信息

Department of Pharmacy, Kobe University Hospital, Kobe, Japan.

Department of Urology, Graduate School of Medicine, Kobe University, Kobe, Japan.

出版信息

JMIR Res Protoc. 2019 Aug 12;8(8):e14636. doi: 10.2196/14636.

DOI:10.2196/14636

PMID:31407671

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6709566/

Abstract

BACKGROUND

Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro.

OBJECTIVE

This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA's preventive efficacy for sunitinib-induced HFSR.

METHODS

This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib.

RESULTS

Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021.

CONCLUSIONS

This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR.

TRIAL REGISTRATION

UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14636.

摘要

背景

手足皮肤反应（HFSR）是多种酪氨酸激酶抑制剂（TKIs）引起的严重副作用。HFSR可导致治疗中断或剂量减少。HFSR还会显著降低生活质量，并与多种TKIs的治疗效果相关。因此，HFSR的管理和预防是一个重要问题；然而，尚未建立有效的预防方法。特定的抗坏血酸衍生物可在体外逆转多种TKI诱导的角质形成细胞生长和病理变化。

目的

本研究旨在评估新型水溶性保湿抗坏血酸衍生物双甘油抗坏血酸酯（Amitose DGA）在接受舒尼替尼治疗的肾细胞癌（RCC）患者中的安全性。本研究还旨在评估Amitose DGA对舒尼替尼诱导的HFSR的预防效果。

方法

这是一项I/II期单中心、非对照、单臂、开放标签试验。我们将总共招募30例接受舒尼替尼治疗且采用2周用药、1周停药方案的RCC患者。参与者将在舒尼替尼治疗的两个周期（即6周）内，除了标准护理流程外，在手掌和足底表面涂抹含Amitose DGA的乳膏，并联合使用一般保湿剂。安全性评估将包括皮肤异常、临床实验室检查和不良事件发生率。疗效评估将包括HFSR的发生情况以及与舒尼替尼相关的治疗结果。