MARC-2: An open-label trial to characterize patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of the first VEGFR-TKI therapy.

Abstract

467 Background: Clinical research in mRCC is leading to increased treatment options. Most patients (pts) are treated with sequenced systemic medications based on the clinical course of the disease. Characterization of pts most likely to benefit from a specific targeted agent has not yet been sufficiently addressed in this area. So far, no reliable biomarkers exist to predict therapy response or resistance in the individual patient. Further investigation is needed to understand drug effects in vivo. In the MARC-2-study, pts treated with everolimus will be characterized by serum and tissue biomarkers in order to identify a pattern possibly suggestive of treatment outcome. Methods: 80 pts are to be enrolled at about 15 study centers in Germany over 2 years. Major inclusion criteria are confirmed predominantly clear cell mRCC, failure of exactly 1 prior VEGFR-TKI therapy, no pretreatment with mTOR inhibitors or bevacizumab. Tumor response is assessed according to RECIST 1.1. Safety assessments include monitoring of adverse events and laboratory parameters. Primary objective is the rate of pts free of disease progression after 6 months of treatment. Secondary objectives are relation of biomarkers to the clinical benefit, progression free survival, overall survival, objective response rate and safety profile. For explorative assessments, blood samples are taken pre-treatment and at prespecified time points during the treatment. Central histopathological classification of tumor samples will be performed. Biomarker projects include: Serum protein profiling by using SELDI-TOF-MS; quantification of Treg cells in blood samples; identification of serum metabolic biomarkers; polymorphisms in genes related to the VEGFR signaling pathway; expression analysis of the mTOR-pathway in tumor samples. Pharmacokinetic consists of everolimus trough levels. Tumor assessments by functional MRI will be performed within a substudy at selected sites. Results: The 1st patient was enrolled in 03/2011. Until 08/2011, 10 sites have been initiated and 9 pts were recruited. Conclusions: The new project MARC-2 was introduced and started successfully in 2011.