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A Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer

ABSTRACT: This study is designed as an open-label, adaptive Simon Two-Stage study to evaluate the efficacy of CTX-009 in patients with metastatic colorectal cancer. A Simon Two-Stage adaptive design will enroll approximately 37 patients into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled.

DISEASE(S): Metastatic Colorectal Cancer,Colon Cancer,Colorectal Neoplasms,Rectal Cancer

PROVIDER: 2746205 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The c-MET signaling axis is increasingly implicated in tumorigenesis and chemioresistance. In this study, we investigated gene expression modifications induced by SU11274 (Selleck Chemicals, Boston, USA), a novel selective c-MET inhibitor, in a pair of isogenic multiple myeloma (MM) cell lines either sensitive (RPMI8226) or multi-resistant, highly c-MET expressing (RPMI8226/R5) cells. On the whole, RPMI8226/R5 cells after SU11274 were characterised by wider and diverse gene expression modifications than RPMI8226, indicating that c-MET over-expression, and its inhibition, is an important aspect of the adaptive response associated to drug resistance. RPMI8226 and RPMI8226/R5 cells are cultured in RPMI 1640 supplemented with10% fetal calf serum (FCS), 100U/ml penicillin and streptomicin (Euroclone UK) and 1mM Hepes buffer at 37 Â°C in a humified 5% CO2 atmosphere. The effect of SU11274 on gene expression of both cell lines was evaluated in three distinct experiments. 500,000 cells/ml in T25 flasks were treated with SU11274 (10 ÂµM final concentration) or vehicle, for 6 h at 37 Â°C. At the end of the incubation time, treated and control untreated cells were washed and resuspended for RNA extraction. Linear mRNA amplification and labeling of fluorescent cDNA targets (Cy5, treated sample, Cy3, untreated sample) were performed using the Amino Allyl aRNA Amplification MessageAmp II Kit (Ambion), and examined Phalanx Human OneArray HOA (Phalanx Biotech Group's ) microarrays. Array scanning was carried out using a ChipReader VersArray Â® 5 micron dual confocal laser scanner with VersArray ChipReader v3.1 analysis software, while the images were analyzed by scanner row VersArray Analyzer v4.5 software (Bio-Rad Laboratories) with intensity average pixels for each spot. Global Fund has been removed from biquadratic polynomial and the normalization of multiple channels was carried out by local regression (loess), the logarithmic transformation was then performed for each level of expression.

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A Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer

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