Background: Axitinib is a standard second-line treatment after sunitinib in patients (pts) with metastatic or advanced renal cell carcinoma (RCC). The previous results of pharmacokinetic (PK) and pharmacodynamic (PD) analysis of axitinib showed that higher exposure and diastolic blood pressure (dBP) were independently associated with longer progression free survival (PFS) and overall survival in metastatic RCC pts (Rini et al., J Clin Pharmacol, 2013). These findings support that axitinib dose titration to increase plasma exposure in pts who tolerate axitinib, and also demonstrate dBP as a potential marker of efficacy. In clinical practice, axitinib dose titration based on dBP is recommended; however, it has limitations because underlying hypertension and anti-hypertensive agents usually affect daily dBP. Therefore, we hypothesize that the dose adjustment of axitinib based on its exposure is more adequate than that based on dBP. Methods: A prospective single arm trial is conducted at 6 institutions in Japan. The starting dose of axitinib is 5mg BID and blood samples are taken at 2h, 4h, 8h, and 12h after the first administration to assay axitinib levels and calculate the area under concentration-time curve from 0 to 12 hours (AUC_0-12) on day 1. We target AUC_0-12 value at the steady state over 150 ng*hr/mL, and suggest a sufficient dose to reach the 150 ng*hr/mL for each patient. After day 15, dose adjustment of axitinib to keep over the target value is performed according to adverse drug reaction for each patient. The primary endpoint is 6-month PFS rate based on axitinib AUC monitoring, and secondary endpoints include toxicity and objective response rate. The target AUC_0-12 value in sunitinib-refractory pts is also investigated, because the value of 150 ng*hr/mL is referred from the previous PK/PD analysis in which the first-line treatments were not only sunitinib. Major eligibility criteria include (1) metastatic or advanced clear cell RCC or RCC with clear cell component; (2) previously treated with sunitinib; and (3) disease progression on sunitinib or within 6 months of last dose of sunitinib. Prior treatment with cytokines is permitted. Twelve of planned 32 pts have been enrolled as of February 2014. Clinical trial information: UMIN000009579.