-Increase in the patient sample size is done in order to achieve 120 PFS events in a shorter time than with the original sample size of 180. -Include the health related quality of life HF-QoL in order to compare the effect of sorafenib and capecitabine versus placebo and capecitabine on hand-foot skin reaction symptoms

AEs and SAEs:The amendment clarified that all data, including relationship, was captured on the AE case report form page, and that in the electronic data capture system, the SAE form was a subset of the AE case report form. Inconsistencies in reporting requirements for AEs were corrected. It was noted that the IB would be updated in accordance with Bayer/Onyx SOPs. Concomitant medication: It was noted that any kind of growth factors could be used during the study. Data monitoring committee: The role and responsibilities of DMC were modified. Dosing: The capecitabine dosing schedule was clarified in the event of a dose delay due to toxicity. It was also clarified that, although capecitabine was to be discontinued due to toxicity, sorafenib/placebo treatment could be continued AND that although sorafenib/placebo was to be discontinued due to toxicity, capecitabine treatment could be continued. Duration of stable disease: Duration was clarified as a period of time. Follow-up: The protocol was amended to allow a two-week window for the assessments that were required during the Follow-up period (Post-Progression Period). Inclusion and exclusion criteria: Some inclusion and exclusion criteria were revised to provide clarity on the criteria (and in some cases, provided new criteria) that defined patients who were eligible versus not eligible for study entry. Specifically, clarifications/revisions were made to Inclusion Criteria 7, 10, and 11, and to Exclusion Criteria 9, 16, 20, and 21. Laboratory tests: Clarity was provided on when coagulation laboratory tests were to occur. Monitoring toxicities: The amendment specified a requirement for patients to have blood pressure monitoring at a weekly clinic visit (rather than at home) during the first 6 weeks. RECIST criteria: The amendment specified radiologic follow-up requirements for patients with bone disease to fulfill requirements for full evaluation of tumor response per modified RECIST criteria

Treatment continuation period: Amendment 3 modified the protocol to allow patients who were receiving treatment with sorafenib and/or capecitabine at the time that the OS results were unblinded, and the sites and the patients were unblinded, to continue to receive the study treatment to which they were originally assigned at randomization until disease progression occurred or the patients discontinued from the study for any reason. This period of the study was referred to as the “treatment-continuation” phase. An updated informed consent form was to be signed by each patient who was eligible and elected to continue on study during the treatment-continuation period. Assessments of survival were not performed during the treatment-continuation period, safety assessments were conducted per the treating physician’s standard practice. Only SAE safety data was collected during this phase, and no prespecified analyses were performed. SAEs were reported to Onyx Drug Safety using paper forms. At the time of discontinuation of the treatment-continuation period, patients did NOT enter a follow-up period, and study medication was no longer provided.