{"title":"The modified combo i3 + 3 design for novel-novel combination dose-finding trials in oncology.","authors":"Jiaxin Liu, Shijie Yuan, Qiqi Deng, Yuan Ji","doi":"10.1016/j.cct.2025.107857","DOIUrl":null,"url":null,"abstract":"<p><p>We consider a modified Ci3 + 3 (MCi3 + 3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3 + 3 design offers a two-stage or three-stage version, depending on the practical need. The first stage begins with single-agent dose escalation, the second stage launches a model-free combination dose finding for both agents, and optionally, the third stage follows with a model-based design. MCi3 + 3 aims to maintain a relatively simple framework to facilitate practical application, while also address challenges that are unique to novel-novel combination dose finding. Through simulations, we demonstrate that the MCi3 + 3 design adeptly manages various toxicity scenarios. It exhibits operational characteristics on par with other combination designs, while offering an enhanced safety profile. The design is motivated and tested for a real-life clinical trial.</p>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":" ","pages":"107857"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contemporary clinical trials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.cct.2025.107857","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
We consider a modified Ci3 + 3 (MCi3 + 3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3 + 3 design offers a two-stage or three-stage version, depending on the practical need. The first stage begins with single-agent dose escalation, the second stage launches a model-free combination dose finding for both agents, and optionally, the third stage follows with a model-based design. MCi3 + 3 aims to maintain a relatively simple framework to facilitate practical application, while also address challenges that are unique to novel-novel combination dose finding. Through simulations, we demonstrate that the MCi3 + 3 design adeptly manages various toxicity scenarios. It exhibits operational characteristics on par with other combination designs, while offering an enhanced safety profile. The design is motivated and tested for a real-life clinical trial.
期刊介绍：
Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.
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