A phase II study of intermittent sunitinib in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC).

Abstract

TPS4684 Background: Sunitinib is a standard of care initial treatment in mRCC. One challenge is balancing the acute and chronic toxicity of therapy with clinical benefit. Pre-clinical and retrospective clinical data support the concept that treatment breaks are feasible and not associated with a reduction in efficacy of sunitinib. It is hypothesized that an intermittent dosing regimen of sunitinib in mRCC pts is feasible, and may lead to prolonged duration of disease control with improved tolerance. Methods: Eligibility criteria include treatment-naïve clear cell mRCC, measurable disease, and adequate organ function. Pts will be treated for 4 cycles of sunitinib (50 mg 4/2) in the absence of unacceptable toxicity or RECIST-defined progression. Pts with ≥ 10% reduction in tumor burden per RECIST following 4 cycles will have sunitinib held, with re-staging CT scans approximately every 10 weeks thereafter to assess tumor burden. Sunitinib will be re-initiated in those patients with an increase in tumor burden of 10% or greater (per RECIST) compared to the scan obtained just prior to holding sunitinib. Pts who have RECIST tumor burden reduction of 10% or more compared to scans at the start of the most recent treatment period will again have sunitinib held. This intermittent sunitinib dosing will continue until RECIST-defined disease progression while on sunitinib. Patients not initially achieving at least a 10% reduction in tumor burden will continue sunitinib. The primary objective is the feasibility of intermittent sunitinib, defined as the proportion of patients eligible for and who undergo intermittent therapy. The alternative hypothesis is a feasibility rate of > 80% vs. the null hypothesis of < 50%. Thirty pts provides 80% power based on a two-sided exact test with a .05 type I error. Secondary endpoints include PFS and toxicity. Twenty five of planned 30 patients have been enrolled.