The primary purpose of the amendment was to add the exclusion of subjects who had a known hypersensitivity to any of the active substances, including 5-FU, ruxolitinib, or any of their excipients.

The primary purpose of the amendment was to provide clarification regarding eligibility criteria, the definition of RMST, the alpha-control plan for secondary endpoints, and the administration of capecitabine. Important changes included: • Defining prior systemic and radiation therapy, measurable and evaluable disease at screening, and subjects who were required to use appropriate contraception. • Clarifying exclusions for cardiac disease. • Adding an exclusion for prior treatment with a JAK inhibitor. • Changing RMST from a secondary analysis of the primary endpoint to an alpha controlled secondary endpoint to be tested after the log rank OS analysis in a sequential testing procedure. • Implementing an alternative, less-conservative alpha-spending plan (HSD using parameter - 4) for secondary endpoints to control familywise error at the overall 0.025 (one-sided level) while maintaining the sequential gatekeeping procedure for testing secondary endpoints. Previously, secondary endpoints were to be tested using the same allocation scheme used for the primary endpoint (HSD using parameter -15), which could have unnecessarily reduced power for the secondary endpoints. • Clarifying that the total daily capecitabine dose (2000 mg/m^2) was to be administered in approximately equal doses BID using only 500 mg capecitabine tablets because of concerns associated with intersubject dose variation using 2 different tablet strengths (150 mg and 500 mg).