Early Phase Clinical Trials

The objective of most phase I oncology trials is to find the maximum tolerated dose (MTD), which is defined as the dose with the dose-limiting toxicity (DLT) probability closest to the target DLT rate. Phase I trials are critically important for determining the MTD for further investigation in subsequent phase II or III trials. Misidentification of the MTD could result in treating a large number of patients at excessively toxic doses in later phase trials, or discarding a treatment that actually is effective by incorrectly deeming it to be too toxic. Numerous phase I trial designs have been proposed to find the MTD. These designs are generally classified into algorithm-based designs, model-based designs, and model-assisted designs (1–3).