This will be a prospective, open label, randomized multicenter phase-II study to evaluate
progression free survival (PFS) in 2nd line treatment in patients with locally advanced or
metastatic clear-cell renal cell cancer (cc-RCC) receiving everolimus (arm A) in comparison
to a tyrosine-kinase inhibitor (TKI) (arm B). Following 2nd line treatment, patients will be
switched to a TKI in arm A and everolimus in arm B. All patients will receive bevacizumab as
standardized first-line treatment.
Another key element of the study is the analysis of predictive biomarkers, which will be
performed in serum and tumor tissue, respectively. Serum samples will be collected at
prespecified timepoints throughout the study and analysed by SELDI-TOF-MS and DIGE. Candidate
proteins are thought to predict therapeutic outcome and candidates are subject for target
validation by Western Blot or ELISA. In addition, formalin-fixed paraffin-embedded (FFPE)
tumor tissue will be collected prospectively and analysed for micro RNA (miRNA). Candidate
miRNAs that predict therapeutic outcome will be validated by quantitative RT-PCR.
Furthermore, circulating tumor cells (CTCs) will be generated from blood drawings during
routine visits. The primary objective is to correlate the marker profile defined from the
FFPE tissue with the profile obtained from CTCs in order to validate expression based markers
ant their change during different treatment lines.