Sample size and accrual
toxicity
Accrual to the study will be halted and trigger a review by the study investigators and the data safety monitoring committee (DSMC) to determine if the study should be modified or permanently closed to further accrual according to the stopping rules in Stopping guidelines for excessive toxicity at the lowest dose level based on a 70% Agrest-Coull [The MTD is defined as the study dose level 