Study design and treatment
Cancer
ADVERSE EVENTS, CANCER
In the phase I trial, the MTD and the RP2D were determined using a dose–escalation strategy with a 3 + 3 design using a modified Fibonacci scheme, with preferential enrollment of Dose modification was allowed for grade 3 or higher adverse events (AEs) per the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTC AE) version 5.0, with two levels of dose reduction, from 300 mg BID to 250 mg BID and from 250 mg BID to 200 mg BID. If more than two dose levels need to be reduced, the study treatment was terminated.The trial protocols were approved by the independent ethics committee at each site and complied with the International Ethical Guidelines for Biomedical Research Involving Human Subjects. The studies were conducted according to Good Clinical Practice guidelines and the Declaration of Helsinki. All patients provided written informed consent prior to any trial activities.