  In traditional dose-finding studies, dose-limiting toxicity (DLT) is
determined within a fixed time observation window where DLT is often defined as
a binary outcome. In the setting of oncology dose-finding trials, often
patients in advanced stage of diseases are enrolled. Therefore, disease
progression may occur within the DLT observation window leading to treatment
discontinuation and rendering the patient unevaluable for DLT assessment. As a
result, additional patients have to be enrolled, increasing the sample size. We
propose and compare several practical methods for handling disease progression
which occurs within the DLT observation window, in the context of the
time-to-event continual reassessment method (TITE-CRM) which allows using
partial observations. The methods differ on the way they define an evaluable
patient and in the way incomplete observations are included. The methods are
illustrated and contrasted in the context of a single simulated trial, and
compared via simulations under various scenarios of dose-progression
relationship, in the setting of advanced soft-tissue sarcoma.
