Table 3 Criteria for dose escalation between patient cohorts and determination of maximum tolerated dose (MTD)
Cohort size (evaluable patients) | Dose limiting toxicities in cycle 1 | Actions |
|---|---|---|
3–6 | 0 | Cohorts 1–3: dose escalation to the next cohort Cohort 4: MTD is established at this dose level |
< 6 | 1 | Expand cohort to include up to 6 evaluable patients and re-evaluate |
6 | 1 | Cohorts 1–3: dose escalation to the next cohort Cohort 4: MTD is established at this dose |
≥ 2 | ≥ 2 | Dose level will be considered a non-tolerated dose; no further recruitment to this cohort and dose escalation will cease Cohort 1: The combination will be considered non-viable (consider incorporation of granulocyte-colony stimulating factor G-CSF) Cohorts 2–4: The previous dose level will be expanded to incorporate six evaluable patients (consider incorporation of G-CSF) |