Operating characteristics
endometrial cancer
ENDOMETRIAL CANCER
Simulations were run to display the performance of the design characteristics. In the initial meeting with the statistical team about the Phase I endometrial cancer trial, the clinical team presented the 5 + 2 design [If 0 of the 5 patients have a DLT per CTCAE and 2 or less of the 5 patients have a DLT per PRO-CTCAE, then accrual into Cohort 2 will begin.If 1 of the 5 patients in Cohort 1 has a DLT per CTCAE and/or 3 of the 5 patients have a DLT per PRO-CTCAE, 2 more patients will be enrolled in Cohort 1 for a total of 7 patients.If 1 of the 7 patients has a DLT per CTCAE and 3 or fewer patients have a DLT per PRO-CTCAE, then accrual into Cohort 2 will begin.The accrual goal for cohort 2 is 7 patients (total If 2 or more patients have a DLT per CTCAE and/or 4 or more patients have a DLT per PRO-CTCAE in cohort 1, then the study will end, and we will conclude that 15 fraction RT (cohort 1) is not safe or feasible.We assumed a set of true DLT probabilities for each endpoint (C-DLT and P-DLT). We evaluated each design under a broad range of hypothesized probability scenarios. Under each scenario, weSimulated trial data for the PRO-CRMB and 5 + 2 stepwise designs.Recorded which dose level (fractions course) was chosen as MTD.Repeated trial simulation many times (i.e., 10,000).Tabulated the percentage of times each course is chosen as the MTD over the 10,000 simulated trials and the percentage of times the trial stopped early for safety. The maximum sample size is Recorded the average number of participants treated on each course and the average sample size over 10,000 simulated trialsThe confidence level used to define the safety stopping guidelines for the PRO-CRMB design was 70%. Percentage of MTD selection at each course for the 5 + 2 design and the Bayesian PRO-CRM with cohorts of size 3.Bold font indicates the level that is the MTD corresponding to a target C-DLT rate of 20% and a target P-DLT rate of 55%.Average number of patients treated at each course for the 5 + 2 design and the Bayesian PRO-CRM with cohorts of size 3.Bold font indicates the level that is the MTD corresponding to a target C-DLT rate of 20% and a target P-DLT rate of 55%.In Scenario 1, both treatment courses have DLT probability rates below the respective safety thresholds In Scenario 4, 10 fractions has a PRO-CTCAE DLT rate 