{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:26:17Z","timestamp":1790130377428,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cutaneous angiosarcoma (CAS) is an endothelial cell\u2010derived, highly aggressive type of vascular tumour. Although chemoradiotherapy with paclitaxel (PTX) is recognized as a first\u2010line therapy for CAS, second\u2010line therapy for CAS remains controversial, and there is no standard therapy for taxane\u2010resistant CAS. Plasminogen activator inhibitor\u20101 (PAI\u20101) is associated with poor clinical outcomes, and elevated levels of PAI\u20101 in both tissue and serum are correlated with poor response to therapy in various cancers, including skin cancers. Since PAI\u20101 protects endothelial cells from Fas ligand\u2010mediated apoptosis, PAI\u20101 inhibition might induce apoptosis of endothelial cell\u2010derived tumours such as CAS. This is a single\u2010arm, open\u2010label, multi\u2010institutional, Phase 2 clinical trial to assess the efficacy and safety of PTX in combination with TM5614 (PAI\u20101 inhibitor) in patients with PTX\u2010resistant CAS. PTX will be administered for 28\u2009weeks, with oral administration of TM5614. The primary endpoint of this study will be the overall response rate (ORR) at 28\u2009weeks after starting treatment (central image evaluation). The secondary endpoint will include the ORR at 28\u2009weeks after starting treatment (investigator evaluation), ORR at 8\u2009weeks and 16\u2009weeks after initiation of treatment (central and investigator evaluation), progression\u2010free 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\u2010sided, 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\u2010site monitoring. This study will contribute to the development of novel combination therapy for PTX\u2010resistant CAS patients, which remains an unmet clinical need.<\/jats:p>","DOI":"10.1111\/exd.14976","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T01:23:11Z","timestamp":1699579391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Efficacy and safety of\n                    <scp>TM5614<\/scp>\n                    in combination with paclitaxel in the treatment of paclitaxel\u2010resistant cutaneous angiosarcoma: Phase\n                    <scp>II<\/scp>\n                    study protocol"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-5833","authenticated-orcid":false,"given":"Taku","family":"Fujimura","sequence":"first","affiliation":[{"name":"Department of Dermatology Tohoku University School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Dermato\u2010Oncology\/Dermatology Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Geriatric and Environmental Dermatology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Geriatric and Environmental Dermatology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Jichi Medical University Saitama Medical Center  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ehime University  Matsuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeto","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Dermato\u2010Oncology\/Dermatology National Hospital Organization Kagoshima Medical Center  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Amagai","sequence":"additional","affiliation":[{"name":"Department of Dermatology Tohoku University School of Medicine  Sendai 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