{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:21:29Z","timestamp":1791580889422,"version":"4.3.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PC210475"],"award-info":[{"award-number":["PC210475"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["CA1719835"],"award-info":[{"award-number":["CA1719835"]}]},{"name":"National Cancer Institute","award":["CA208396"],"award-info":[{"award-number":["CA208396"]}]},{"name":"National Cancer Institute","award":["R44CA195793"],"award-info":[{"award-number":["R44CA195793"]}]},{"name":"Cancer Center Support Grant","award":["CA044579"],"award-info":[{"award-number":["CA044579"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Ceramide is a sphingolipid metabolite that deactivates multiple oncogenic signaling pathways and promotes cell death. In-vivo data demonstrate single-agent anti-cancer activity and enhanced efficacy with combination strategies. This phase I dose-escalation trial evaluated Ceramide nanoLiposomes (CNL) in patients with advanced solid tumors and no standard treatment option.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The primary objective was to establish the maximum tolerated dose. Secondary objectives included determining the recommended phase II dose, the safety and tolerability, the pharmacokinetic profile and preliminary anti-tumor efficacy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>15 patients with heavily pretreated metastatic disease enrolled. Safety data were analyzed for all patients, while pharmacokinetic data were available for 14\u00a0patients. There were no grade 3 or higher treatment-related adverse events. The maximum tolerated dose was not reached and there were no dose-limiting toxicities. The most common grade 1 or 2 treatment-related adverse events included headache, fatigue, constipation, nausea and transaminitis. The maximum concentration and area under the curve increased with dose. Clearance was consistent between doses and was observed mainly through the liver without significant hepatotoxicity. The half-life ranged from 20 to 30\u00a0h and the volume of distribution was consistent with a lipophilic drug.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>CNL exhibited an encouraging safety profile and pharmacokinetic parameters, with some signals of efficacy including prolonged stable disease in 1 patient with\u00a0refractory pancreatic cancer. Pre-clinical data indicate potential synergy between CNL and multiple systemic therapies including chemotherapy, targeted therapy, and immunotherapy. Future studies are planned investigating CNL in combination strategies. <\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>This study is registered under ClinicalTrials.gov ID: NCT02834611.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-023-04588-7","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T05:01:45Z","timestamp":1695358905000},"page":"23-29","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A phase I study of the ceramide nanoliposome in patients with advanced solid tumors"],"prefix":"10.1007","volume":"93","author":[{"given":"Aaron","family":"Ciner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Gourdin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylisa","family":"Parette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0013-1807","authenticated-orcid":false,"given":"Yixing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"issue":"3","key":"4588_CR1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrm.2017.107","volume":"19","author":"YA Hannun","year":"2018","unstructured":"Hannun YA, Obeid LM (2018) Sphingolipids and their metabolism in physiology and disease. 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KN, who holds the IND for the phase I clinical trial, is developing CNL as Ceraxa\u2122. Jeff Davidson is Chief Operating Officer of KN and Mylisa Parette previously served as Vice President of Research at KN. There are no other financial or non-financial conflicts of interest directly or indirectly related to this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}