{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:14:09Z","timestamp":1778930049449,"version":"3.51.4"},"reference-count":27,"publisher":"American Association for Cancer Research (AACR)","issue":"23","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In recent years, investigators have recognized the rigidity of single-agent, safety-only, traditional designs, rendering them ineffective for conducting contemporary early-phase clinical trials, such as those involving combinations and\/or biological agents. Novel approaches are required to address these research questions, such as those posed in trials involving targeted therapies. We describe the implementation of a model-based design for identifying an optimal treatment combination, defined by low toxicity and high efficacy, in an early-phase trial evaluating a combination of two oral targeted inhibitors in relapsed\/refractory mantle cell lymphoma. Operating characteristics demonstrate the ability of the method to effectively recommend optimal combinations in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined targeted therapies. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of a melanoma helper peptide vaccine plus novel adjuvant combinations. Clin Cancer Res; 23(23); 7158\u201364. \u00a92017 AACR.<\/jats:p>","DOI":"10.1158\/1078-0432.ccr-17-1069","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T20:40:24Z","timestamp":1500669624000},"page":"7158-7164","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Implementation of a Model-Based Design in a Phase Ib Study of Combined Targeted Agents"],"prefix":"10.1158","volume":"23","author":[{"given":"Nolan A.","family":"Wages","sequence":"first","affiliation":[{"name":"1Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig A.","family":"Portell","sequence":"additional","affiliation":[{"name":"2Division of Hematology\/Oncology, University of Virginia, Charlottesville, Virginia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Williams","sequence":"additional","affiliation":[{"name":"2Division of Hematology\/Oncology, University of Virginia, Charlottesville, Virginia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Conaway","sequence":"additional","affiliation":[{"name":"1Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina R.","family":"Petroni","sequence":"additional","affiliation":[{"name":"1Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","published-online":{"date-parts":[[2017,11,30]]},"reference":[{"key":"2026041420345639100_bib1","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1158\/1078-0432.CCR-15-1295","article-title":"Optimal dosing for targeted therapies in oncology: drug development cases leading by example","volume":"22","author":"Sachs","year":"2016","journal-title":"Clin Cancer Res"},{"key":"2026041420345639100_bib2","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1158\/1078-0432.CCR-15-2644","article-title":"Rendering the 3 + 3 design to rest: more efficient approaches to oncology dose-finding trials in the era of targeted therapy","volume":"22","author":"Nie","year":"2016","journal-title":"Clin Cancer Res"},{"key":"2026041420345639100_bib3","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1200\/JCO.2013.54.6051","article-title":"Adaptive dose-finding studies: a review of model-guided phase I 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