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Daniells, Libby ; Jaki, Thomas ; Dayimu, Alimu ; Demiris, Nikos ; Bristi, Basu ; Symeonides, Stefan ; Mozgunov, Pavel

Seamless monotherapy-combination phase I dose-escalation model-based design

Daniells, Libby , Jaki, Thomas , Dayimu, Alimu , Demiris, Nikos, Bristi, Basu, Symeonides, Stefan and Mozgunov, Pavel (2025) Seamless monotherapy-combination phase I dose-escalation model-based design. Clinical Trials 22 (4), pp. 430-441.

Date of publication of this fulltext: 22 Sep 2025 05:09
Article
DOI to cite this document: 10.5283/epub.77714


Abstract

Phase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with ...

Phase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with another agent. We develop a three-parameter Bayesian logistic regression model that allows for more efficient use of information between monotherapy and combination parts of the study. The model allows the monotherapy and combination data to drive dose escalation of the combination of treatments, reflecting the known dose-toxicity relationship between the monotherapy and combination setting. Through a thorough simulation study in which the proposed model is compared to two comparative approaches, the three-parameter Bayesian logistic regression model is shown to accurately select doses in the target toxicity interval, performing similar to comparative approaches in terms of proportion of target dose/combination selection, while more than halving the proportion of doses selected that were greater than the target toxicity, thereby improving safety concerns.



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Details

Item typeArticle
Journal or Publication TitleClinical Trials
Publisher:Sage
Open Access Type:CC-License
Volume:22
Number of Issue or Book Chapter:4
Page Range:pp. 430-441
Date12 July 2025
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1177/17407745251350604DOI
KeywordsDose-finding, combination study
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-777140
Item ID77714

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