%0 Journal Article
%T Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer
%A Charlotte M Huijts
%A Saskia J Santegoets
%A Alfons J van den Eertwegh
%A Laura S Pijpers
%A John B Haanen
%A Tanja D de Gruijl
%A Henk M Verheul
%A Hans J van der Vliet
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-505
%X This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels.This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus.ClinicalTrials.gov Identifier NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number NTR3085.Approximately 2% of all adult malignancies are kidney tumors and these account for about 116.000 deaths worldwide per year [1]. Renal cell carcinoma (RCC) is the most common primary tumor arising in the kidney and can be classified into four histological subtypes, i.e. clear cell (60-80%), papillary (10-15%), chromophobe (5-10%) and collecting duct carcinoma (< 1%). Approximately 30% of all patients with RCC has metastatic disease at presentation and ~50% of patients undergoing curative surgery can be expected to experience relapse at distant
%U http://www.biomedcentral.com/1471-2407/11/505