Phase I clinical trial designs in oncology: A systematic literature review from 2020 to 2022

Abstract

Abstract Background: Phase I clinical trials aim to find the highest dose of a novel drug that may be administrated safely without having serious adverse effects. Model-based designs have recently become popular in dose-finding procedures. Our objective is to provide an overview of phase I clinical trials in oncology. Methods: A retrospective analysis of phase I clinical trials in oncology was performed by using the PubMed database between January 1, 2020, and December 31, 2022. We extracted all papers with the inclusion of trials in oncology and kept only those in which dose escalation or/ and dose expansion were conducted. We also compared the study parameters, design parameters, and patient parameters between industry-sponsored studies and academia-sponsored research. Result: Among the 1450 papers retrieved, 256 trials described phase I clinical trials in oncology. Overall, 71.1% of trials were done with a single study cohort, 56.64% of trials collected a group of at least 20 study volunteers, 55.1% were sponsored by industry, and 99.2% of trials had less than 10 patients who experienced DLTs. The traditional 3 + 3 (73.85%) was still the most prevailing method for the dose-escalation approach. More than 50% of the trials did not reach MTDs. Industry-sponsored study enrolled more patients in dose-escalation trials with benefits of continental cooperation. Compared to previous findings, the usage of model-based design increased to about 10%, and the percentage of traditional 3 + 3 design decreased to 74%. Conclusions: Phase I traditional 3 + 3 designs perform well, but there is still room for development in novel model-based dose-escalation designs in clinical practice.

Keywords

• Dose-escalation design
• dose expansion
• dose-limiting toxicity
• maximum tolerated dose
• phase i trials