Trial Information

Correlating Renal Cell Cancer Treatment Efficacy With Sunitinib Therapeutic Levels and Outcomes

Rationale: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used for first-line
systemic therapy in metastatic renal cell carcinoma. It is metabolised to a
pharmacologically active metabolite, SU012662, which is of equal potency to the parent
compound. At a standard 50mg daily dose, variability in plasma levels between patients is
approximately ten-fold. In clinical trials, over 30% of patients require a dose reduction
due to toxicity. However, some patients can tolerate up to 100mg without excessive toxicity.
It is unknown if sunitinib clearance changes with time. Pre-clinical experiments observed
tyrosine kinase inhibition at a plasma concentration of 50-100ng/ml.

Design: This is a prospective non-randomized, Phase II clinical study. Decision to treat
patients with single-agent sunitinib is pre-determined by treating specialists before
entering this study. Toxicity and trough sunitinib/metabolite levels will be measured every
six weeks during treatment.

Aim: This study will prospectively examine the relationship between steady-state trough
levels of sunitinib/metabolites and the time on treatment, in addition to changes in trough
levels over time. Trough levels will also be correlated with other measures of efficacy and
treatment-related toxicity. Furthermore, we aim to confirm that the putative target of
50ng/ml correlates with toxicity and time on sunitinib.