A phase II multicenter study of the efficacy and safety of sunitinib given on an individualized schedule as first-line therapy for metastatic renal cell cancer.

TPS4594 Background: Retrospective reviews have shown poorer than expected response rate (RR), progression free survival (PFS) and overall survival (OS) in Sunitinib treated (Rx) Renal Cell Cancer (RCC) patients (pts) who experience minimal toxicity. This study is based on an individualized (individ) Rx strategy where dose/schedule modifications (DSM) were done to maximize dose and minimize time off Rx in 172 pts (Bjarnason ASCO-GU 2011). Pts started on 50mg 28 days (d) on/14d off. DSM were done to keep toxicity (fatigue, skin, GI, hematology) at ≤ grade-2. DSM-1 was 50mg 14d/7d with individ increases in d on Rx based on toxicity. DSM-2 was 50mg 7d/7d with individ increases in d on Rx. DSM-3 was 37.5mg continuously with individ 7d breaks. DSM-4 was 25mg continuously with individ 7d breaks.In pts with clear cell histology PFS was inferior (5.8 mo) on the standard 50mg 28d/14d schedule vs. DSM schedules (>14 months, p=0.0002) These data, confirmed in 185 pts at MD Anderson (Jonasch KCA 2012), suggest that pts with minimal toxicity after 28d on Rx may benefit from dose escalation. Methods: A prospective phase II study has opened in 11 centers in Canada. DSM are done as described above. Pts with minimal toxicity after 28d are escalated to 62.5 mg and then 75 mg on a 14d /7d schedule. We expect to dose escalate 25% of pts and maintain another 40% of pts on a 50 mg dose that would otherwise have been dose reduced. The primary objective is the PFS associated with this strategy. Secondary objectives include dose intensity, RR, OS, toxicity, and quality of life. Samples for Sunitinib pharmacokinetics are obtained during the first course and again when the ideal sunitinib schedule has been established. Samples for biomarker and DNA correlative studies are collected. Based on the standard arm of the EFFECT trial (identical eligibility criteria), we assume a median PFS of 8.5 months in pts Rx using standard dosing. We expect pts treated with the indiv dosing will have a median PFS of 14 months. With alpha=0.05, a two-sided, single-arm non-parametric survival test would have over 90% power to detect this difference with a total of 110 pts on study. Study enrollment began in July 2012 with 25 pts currently on study. Clinical trial information: NCT01499121.