Study outcomes
death, DLTs
ADVERSE EVENT
The primary objective was to determine the MTD of nintedanib, and this was based on the occurrence of DLTs during the first treatment cycle. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 16.7% (n = 1/6) during the first treatment cycle. Patients who did not complete the first treatment cycle for reasons other than DLT were to be excluded from the MTD evaluation set used in the primary endpoint analysis. The objective response (OR) in all patients treated (treated set, TS), duration of response, and progression-free survival (PFS) were evaluated as exploratory efficacy endpoints. OR was confirmed by imaging 4 weeks or later after the first occurrence of the response. Response was assessed according to RECIST version 1.1.Safety was evaluated in the TS based on the occurrence of AEs, which were defined according to the Common Terminology Criteria for Adverse Events version 4.0 and the Medical Dictionary for Regulatory Activities version 22.0, and AEs relating to DLTs. AEs that started before the first drug intake and deteriorated during treatment were also evaluated as treatment-emergent AEs (TEAEs). A serious AE (SAE) was defined as any AE that resulted in death or hospitalization or presented a significant hazard to the patient.