Safety and feasibility of anlotinib in children with high risk, recurrent or refractory sarcomas: an open-label, single-centre, single-arm, phase Ia/Ib trial

作者：Suying Lü, Yi Que, Dongyang Liu, Feifei Sun, Xueting Yao, Liting Deng, Jing Zhan, Junting Huang, Ruiqing Cai, Xin Wang, Shixing Zhu, Zijun Zhen, Jia Zhu, Juan Wang, Yizhuo Zhang · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103258 · 被引用次数：4 · 研究领域：Lung Cancer Research Studies、Peptidase Inhibition and Analysis、RNA modifications and cancer

Background Anlotinib is a novel highly potent multitargeted tyrosine kinase inhibitor. However, the safety, recommended dosage, pharmacokinetics (PK) characteristics, and efficacy of anlotinib in paediatric patients have not been fully studied. We aimed to evaluate the safety, PK, and feasibility of anlotinib in children with high risk, recurrent or refractory sarcomas. Methods This was an open-label, single-centre, single-arm, phase I study utilizing a "3 + 3" design. Participants were recruited at the Sun Yat-sen University Cancer Centre in China. Paediatric patients aged 5–18 years with a diagnosis of high-risk, relapsed, or refractory sarcomas were eligible for enrolment in this study. Anlotinib was administered orally once daily on a 2-week-on/1-week-off schedule. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reason. For patients receiving anlotinib as maintenance therapy, the maximum treatment duration was one year. The primary endpoint of phase Ia was the maximum tolerated dose (MTD) of anlotinib. The primary endpoint of phase Ib was the recommended phase II dose (RP2D) of anlotinib. Secondary endpoints included safety, PK, and efficacy. Efficacy endpoints, such as objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), were assessed at every 2 cycles for patients with measurable lesions until disease progression or intolerable toxicity. Patien...