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However, no standard second-line treatment for paclitaxel-resistant patients has ever been established. Since primary cutaneous angiosarcoma expresses a high level of vascular endothelial growth factor receptor, the multitargeted tyrosine kinase inhibitor pazopanib seemed to be the most promising agent, and several retrospective studies have demonstrated its activity against this disease. However, the efficacy and safety of pazopanib in paclitaxel-resistant patients with primary cutaneous angiosarcoma have never been evaluated in a clinical trial.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In February 2018 the Dermatologic Oncology Group of Japan Clinical Oncology Group started a single-arm confirmatory trial to evaluate the efficacy and safety of pazopanib as a second-line treatment for patients with primary cutaneous angiosarcoma whose disease was resistant to paclitaxel or who were unable to tolerate paclitaxel (JCOG1605, JCOG-PCAS). Patients with primary cutaneous angiosarcoma not associated with lymphedema or radiation, progressing despite first-line paclitaxel monotherapy are included in the study. No prior systemic chemotherapy other than paclitaxel is permitted. Pazopanib is administered orally at an initial dosage of 800\u2009mg once daily. Dose modifications for adverse events are made according to the dose reduction criteria described in the protocol. Treatment is continued until recurrence, disease progression, unacceptable toxic effects, patient refusal, or death. The primary endpoint is progression-free survival, secondary endpoints include overall survival, response rate, disease control rate, adverse events, and serious adverse events. We plan to recruit 30 participants in 5.5\u2009years from 23 Japanese institutions. The follow-up period is set as 1\u2009year after completion of accrual. The study protocol was approved by the Japan Clinical Oncology Group Protocol Review Committee in December 2017. Ethical approval for this study was granted by Ethics Committee of each institute.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Discussion<\/jats:title>\n<jats:p>If the primary endpoint is met, pazopanib will be regarded as a standard of care for paclitaxel-resistant patients for whom no standard second-line treatment is established.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trials registration<\/jats:title>\n<jats:p>Registry number: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000035879\">UMIN000031438<\/jats:ext-link> [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.umin.ac.jp\/ctr\/index.htm\">http:\/\/www.umin.ac.jp\/ctr\/index.htm<\/jats:ext-link>]. Date of Registration: 23\/Feb\/2018. Date of First Participant Enrollment: 8\/Mar\/2018.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12885-020-07136-1","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T12:06:02Z","timestamp":1594641962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A single-arm confirmatory trial of pazopanib in patients with paclitaxel-pretreated primary cutaneous angiosarcoma: Japan Clinical Oncology Group study (JCOG1605, JCOG-PCAS protocol)"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-9430","authenticated-orcid":false,"given":"Kohei","family":"Oashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Namikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Teramoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arata","family":"Tsutsumida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Dermatologic Oncology Group of the Japan Clinical Oncology Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"issue":"5","key":"7136_CR1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/1097-0142(19870301)59:5<1046::AID-CNCR2820590533>3.0.CO;2-6","volume":"59","author":"CA Holden","year":"1987","unstructured":"Holden CA, Spittle MF, Jones EW. 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The study protocol was approved by the JCOG Protocol Review Committee in December 2017 and by the Institutional Review Board of National Cancer Center Hospital on February 9th, 2018. Written informed consent has been obtained from all enrolled participants. At the time of submission (June 2020), a total of 21 institutions are participating in this trial. The participating institutions are as follows: Hokkaido University Hospital, Asahikawa Medical University Hospital, Sapporo Medical University School of Medicine, University of Tsukuba, Saitama Medical University International Medical Center, Saitama Medical University, National Cancer Center Hospital, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Keio University Hospital, The University of Tokyo Hospital, Niigata Cancer Center Hospital, Toyama Prefectural Central Hospital, Shinshu University School of Medicine, Shizuoka Cancer Center, Nagoya University School of Medicine, Kyoto University Hospital, Osaka International Cancer Institute, Faculty of Medicine, Fukuoka University, Kyushu University Hospital, Kumamoto University Hospital and National Hospital Organization Kagoshima Medical Center.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Dr. Namikawa has received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis Pharmaceutical, Toray Industries, Takara Bio, Eisai, and Chugai Pharmaceutical, unrelated to the submitted work.Dr. Tsutsumida has received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis Pharmaceutical, unrelated to the submitted work.Dr. Takahashi has received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Merck Sharp & Dohme, and Novartis Pharmaceutical, unrelated to the submitted work.Dr. Yamazaki has received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis Pharmaceutical, Takeda Pharmaceutical, and Chugai Pharmaceutical, unrelated to the submitted work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"652"}}