皮肤血管肉瘤（CAS）是一种内皮细胞来源的、高度侵袭性的血管肿瘤。尽管紫杉醇（PTX）放化疗被认为是 CAS 的一线治疗，但 CAS 的二线治疗仍存在争议，并且对于紫杉类耐药的 CAS 尚无标准治疗方法。纤溶酶原激活剂抑制剂-1 (PAI-1) 与不良临床结果相关，组织和血清中 PAI-1 水平升高与各种癌症（包括皮肤癌）治疗反应不佳相关。由于 PAI-1 保护内皮细胞免受 Fas 配体介导的细胞凋亡，因此抑制 PAI-1 可能会诱导内皮细胞源性肿瘤（如 CAS）的细胞凋亡。这是一项单臂、开放标签、多机构、2 期临床试验，旨在评估 PTX 与 TM5614（PAI-1 抑制剂）联合治疗 PTX 耐药 CAS 患者的疗效和安全性。 PTX 将给药 28 周，同时口服 TM5614。本研究的主要终点是开始治疗后 28 周的总体缓解率 (ORR)（中心图像评估）。次要终点将包括开始治疗后 28 周的 ORR（研究者评估）、治疗开始后 8 周和 16 周的 ORR（中心和研究者评估）、无进展生存期、总生存期、疾病控制率和安全性概况。假设响应率为 13.6% 的原假设和 45% 的备择假设，则基于精确二项分布，至少需要 15 名患者才能实现 5% 的双边 I 类误差和 70% 的功效。数据质量控制将采用集中（远程）和现场监测相结合的方式进行。这项研究将有助于为 PTX 耐药 CAS 患者开发新型联合疗法，这仍然是一个未满足的临床需求。© 2023 作者。约翰·威利出版的《实验皮肤病学》

Cutaneous angiosarcoma (CAS) is an endothelial cell-derived, highly aggressive type of vascular tumour. Although chemoradiotherapy with paclitaxel (PTX) is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial, and there is no standard therapy for taxane-resistant CAS. Plasminogen activator inhibitor-1 (PAI-1) is associated with poor clinical outcomes, and elevated levels of PAI-1 in both tissue and serum are correlated with poor response to therapy in various cancers, including skin cancers. Since PAI-1 protects endothelial cells from Fas ligand-mediated apoptosis, PAI-1 inhibition might induce apoptosis of endothelial cell-derived tumours such as CAS. This is a single-arm, open-label, multi-institutional, Phase 2 clinical trial to assess the efficacy and safety of PTX in combination with TM5614 (PAI-1 inhibitor) in patients with PTX-resistant CAS. PTX will be administered for 28 weeks, with oral administration of TM5614. The primary endpoint of this study will be the overall response rate (ORR) at 28 weeks after starting treatment (central image evaluation). The secondary endpoint will include the ORR at 28 weeks after starting treatment (investigator evaluation), ORR at 8 weeks and 16 weeks after initiation of treatment (central and investigator evaluation), progression-free survival, overall survival, disease control rate and safety profiles. Assuming the null hypothesis of a response rate of 13.6% and an alternative hypothesis of 45%, a minimum of 15 patients are required to achieve a two-sided, Type I error of 5% and power of 70% based on the exact binomial distribution. Data quality control will be conducted by a combination of centralized (remote) and on-site monitoring. This study will contribute to the development of novel combination therapy for PTX-resistant CAS patients, which remains an unmet clinical need.© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.