{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:48:08Z","timestamp":1783608488952,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA015083"],"award-info":[{"award-number":["P30 CA015083"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Nab<\/jats:italic>\n \u2010sirolimus (ABI\u2010009,\n nab<\/jats:italic>\n \u2010rapamycin; Aadi Bioscience Inc. [Aadi]) is a human albumin\u2010bound form of sirolimus nanoparticles, a potent mTOR inhibitor. This phase I trial was conducted to define dose\u2010limiting toxicities (DLT), maximum tolerated or recommended phase II dose (MTD\/RP2D), and pharmacokinetics of\n Nab<\/jats:italic>\n \u2010sirolimus in combination with temozolomide and irinotecan.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Using a rolling 6 design,\n Nab<\/jats:italic>\n \u2010sirolimus was administered intravenously (IV) on days (D) 1 and 8 of cycle (C) 1. In subsequent cycles,\n Nab<\/jats:italic>\n \u2010sirolimus was administered D1 and D8 in combination with temozolomide (125\u2009mg\/m\n 2<\/jats:sup>\n \/dose, maximum 250\u2009mg\/dose) and irinotecan (90\u2009mg\/m\n 2<\/jats:sup>\n \/dose) orally, daily on D1\u20135. Cycle duration was 21\u2009days. Three dose levels (DL) of\n Nab<\/jats:italic>\n \u2010sirolimus were investigated (DL1: 35\u2009mg\/m\n 2<\/jats:sup>\n \/dose, DL\u20101: 20\u2009mg\/m\n 2<\/jats:sup>\n \/dose, and DL\u20102: 15\u2009mg\/m\n 2<\/jats:sup>\n \/dose). The observation period for estimating the MTD\/RP2D was defined by cycles 1 and 2.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty\u2010three patients were enrolled, 32 were eligible. Dose determination included 17 evaluable patients, median (range) age 12 (2\u201320) years and six additional patients were enrolled (four evaluable for toxicity) on a pharmacokinetic cohort. C1 or C2 DLTs were primarily thrombocytopenia including 2\/5 patients at DL1, 2\/6 patients at DL\u20101, and 1\/6 patients at DL\u20102. One patient (DL1) with Ewing Sarcoma had a partial response and remained on study for 35\u2009cycles. Rapamycin clearance was dose dependent. Irinotecan clearance and its active metabolite SN\u201038 exposure were not affected by coadministration with\n Nab<\/jats:italic>\n \u2010sirolimus.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The MTD for\n Nab<\/jats:italic>\n \u2010sirolimus was 15\u2009mg\/m\n 2<\/jats:sup>\n \/dose IV on D1 and D8 in combination with temozolomide 125\u2009mg\/m\n 2<\/jats:sup>\n \/dose and oral irinotecan 90\u2009mg\/m\n 2<\/jats:sup>\n \/dose daily for 5\u2009days during 21D cycles.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n ClinicalTrials.gov identifier NCT02975882<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.70376","type":"journal-article","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T05:38:41Z","timestamp":1730525921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Phase 1 Study of\n ABI<\/scp>\n \u2010009 (\n Nab<\/i>\n \u2010sirolimus) in Combination With Temozolomide and Irinotecan in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including\n CNS<\/scp>\n Tumors\u2014A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study\n ADVL1514<\/scp>"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-3888","authenticated-orcid":false,"given":"Stuart\u00a0L.","family":"Cramer","sequence":"first","affiliation":[{"name":"Prisma Health\u2010Midlands Children's Center for Cancer and Blood Disorders Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa\u00a0Terry","family":"Reddy","sequence":"additional","affiliation":[{"name":"Neurology\/Child Neurology UCSF Medical Center\u2010Mission Bay San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles\u00a0Gene","family":"Minard","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine\/Dan L Duncan Comprehensive Cancer Center Dan L. Duncan Institute Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Voss","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute Children's Hospital of Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[{"name":"Cancer Center, Clinical Trials Administration Saint Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Liu","sequence":"additional","affiliation":[{"name":"Children's Oncology Group Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Denic","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel\u00a0M.","family":"Reid","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda\u00a0J.","family":"Weigel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hem\/Onc\/BMT University of Minnesota Medical Center\u2010Fairview Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24874"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2062"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13021886"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.216020"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114971"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01827-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2008.05.010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3110"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00576"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.116"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-008-9749-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.4649"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22407"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.6103"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.4889"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1381"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2438-4"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13040470"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1996.d01-52.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000476"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T12:55:44Z","timestamp":1765284944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":21,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/cam4.70376"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70376","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70376"}}