Incorporating a patient dichotomous characteristic in cancer phase I clinical trials using escalation with overdose control (Q454783)

Summary: We describe a design for cancer phase I clinical trials that takes into account patients heterogeneity thought to be related to treatment susceptibility. The goal is to estimate the maximum tolerated dose (MTD) given patient's specific dichotomous covariate values. The design is Bayesian adaptive and is an extension of escalation with overdose control (EWOC). We assess the performance of this method by comparing the following designs via extensive simulations: (1) Designs using a covariate; patients are accrued to the trial sequentially and the dose given to a patient depends on his/her baseline covariate values, (2) Designs ignoring the covariates; patients are accrued to the trial sequentially and the dose given to a patient does not depend on his/her baseline covariate value, and (3) Designs using separate trials; in each group, patients are accrued to the trial sequentially and EWOC is implemented in each group. These designs are compared with respect to safety of the trial and efficiency of the estimates of the MTDs via extensive simulations. We found that ignoring a significant baseline binary covariate in the model results in a substantial number of patients being overdosed. On the other hand, accounting for a non-significant covariate in the model has practically no effect on the safety of the trial and efficiency of the estimates of the MTDs.