Suying Lu, Juan Wang, Junting Huang, Feifei Sun, Jia Zhu, Yi Que, Hui Li, Ying Guo, Ruiqing Cai, Zijun Zhen, Xiaofei Sun, Yizhuo Zhang
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The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612.</p><p><strong>Findings: </strong>Between January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30 mg/m<sup>2</sup>. The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of <i>TP53</i> mutation may be an adverse prognostic factor.</p><p><strong>Interpretation: </strong>The VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30 mg/m<sup>2</sup> once every 3 weeks.</p><p><strong>Funding: </strong>CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246015/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study.\",\"authors\":\"Suying Lu, Juan Wang, Junting Huang, Feifei Sun, Jia Zhu, Yi Que, Hui Li, Ying Guo, Ruiqing Cai, Zijun Zhen, Xiaofei Sun, Yizhuo Zhang\",\"doi\":\"10.1016/j.eclinm.2024.102701\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients.</p><p><strong>Methods: </strong>This open-label, single-center, single-arm phase I study utilizing a \\\"3 + 3\\\" design enrolled children with relapsed/refractory (R/R) solid tumors. 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引用次数: 0
摘要
背景：长春新碱、聚乙二醇脂质体多柔比星（PLD）和环磷酰胺（VPC）联合疗法从未在儿童患者中进行过研究：这项采用 "3 + 3 "设计的开放标签、单中心、单臂 I 期研究招募了复发/难治性（R/R）实体瘤患儿。研究了三种剂量水平的PLD（Duomeisu®）（30、40或50毫克/平方米）与环磷酰胺（1500毫克/平方米）、美司那（1500毫克/平方米）和长春新碱（1.5毫克/平方米，最多2毫克）的联合用药，每3周一次。主要终点包括安全性、PLD（多美舒®）的最大耐受剂量（MTD）和PLD（多美舒®）的第二阶段推荐剂量（RP2D），以便进行第二阶段的进一步研究。次要终点为客观反应率（ORR）和疾病控制率（DCR）。该研究已在ClinicalTrials.gov注册，编号为NCT04213612.Findings：2020年1月7日至2021年11月18日期间，34名患者符合条件并可进行毒性评估，26名患者可进行反应评估。PLD（Duomeisu®）的MTD为30毫克/平方米。最常见的不良事件（AE）是3级或4级中性粒细胞减少（61.8%）。最常见的1级或2级非血液学AE和心脏毒性反应分别是呕吐（35.3%）和心电图T波异常（20.6%）。VPC方案两个周期后的ORR和DCR分别为50.0%和92.3%。靶向基因面板测序显示，TP53突变的激活可能是一个不利的预后因素：VPC方案在R/R实体瘤患儿中显示出良好的安全性和初步疗效。PLD（多美舒®）联合环磷酰胺和长春新碱的RP2D为30 mg/m2，每3周一次：石家庄中生欧意药业有限公司，国家重点研发计划[编号：2022YFC2705005]，国家自然科学基金[编号：82203303]，广东省基础与应用基础研究基金[编号：2021A1515110234]。
Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study.
Background: The combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients.
Methods: This open-label, single-center, single-arm phase I study utilizing a "3 + 3" design enrolled children with relapsed/refractory (R/R) solid tumors. Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50 mg/m2) in combination with cyclophosphamide (1500 mg/m2), mesna (1500 mg/m2), and vincristine (1.5 mg/m2, maximum 2 mg) once every 3 weeks. The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612.
Findings: Between January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30 mg/m2. The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of TP53 mutation may be an adverse prognostic factor.
Interpretation: The VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30 mg/m2 once every 3 weeks.
Funding: CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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