Study methodology
DLTs, toxicity, toxicities, hyperglycemia, PD
HYPERGLYCEMIA, DISEASE PROGRESSION, ADVERSE EVENT
After a screening period of up to 28 days, three eligible patients began treatment with copanlisib at 45 mg (dose level 1) by 1 h intravenous infusion on days 1, 8, and 15 of a 28-day cycle. Tolerability was assessed at the end of the first cycle, and if no dose-limiting toxicities (DLTs) occurred, three additional patients were enrolled and treated with copanlisib at 60 mg (dose level 2). If one DLT developed, an additional three patients were enrolled and treated at each dose level. Copanlisib was considered not to be tolerated and the study stopped if two or more out of three patients or two or more out of six patients showed DLTs.Once the recommended dose level was established, 20 patients were enrolled in the expansion part (phase II) of the study, which included patients from the dose-escalation phase. During the expansion part, patients were treated with copanlisib until disease progression (PD), clinical progression (e.g., deterioration of ECOG performance status to ≥ 3), unacceptable toxicity, or other reasons for treatment withdrawal.As transient post-infusion hyperglycemia is a known adverse event (AE) with copanlisib, a low carbohydrate diet was recommended for the first 48 h after copanlisib infusion.