Financing: Research Foundation - Flanders (FWO)

Project reference Nr.: G.0824.09
Start: 2009-01-01
End: 2012-12-31

Description:

Advanced bioinformatics methods successfully applied in earlier work (20,26,27) will be applied on a larger scale.   For this purpose a novel set of unique metastatic biosamples will be used, to be prospectively collected from 250   chemo naive metastatic CRC patients in the framework of an investigator driven, industry sponsored phase I-II   dose escalation study for irinotecan-cetuximab combination therapy (Everest II).   In this trial biopsies of liver or other metastatic sites will be obtained at 3 different time points, in analogy to a   previous trial perfomed by this group (Everest I)(20). Samples will be obtained at baseline (b1), at the third   treatment administration (b2) and upon progression of disease (b3). Agreement was sought and obtained from   the sponsor for an independent investigator driven biomarker analysis of these samples.   The bioinformatics methodology to integrate the prospectively collected mutation,and microarray data will be fine   tuned and customised for the purpose of this study for the purpose of (i) generating new insights in the yet   unknown working mechanism of a promising drug (ii) applying advanced bioinformatics algorithms to generate   the molecular signature for (a) sensitivity to EGFR inhibitors in chemo naive mCRC. (b) acquired resistance to   EGFR inhibitors in mCRC. (iii) to identify druggable pathways in metastatic colorectal cancer   The combination of the pre-mentioned factors puts the proposed study in a unique position to generate the new   scientific observations needed to reach its objectives. Moreover:   - The biosamples to be used constitute the only existing series worldwide of prospectively collected plasma,   primary and metastatic tumour samples of patients treated with the irinotecan-cetuximab combination therapy.   7   - Obtained from both a chemonaive and chemorefractory (previous study, Everest I) patient population,   potentially divergent action mechanisms can be detected.   - Repetitive metastatic tumour samples will be obtained, allowing the generation of post treatment (week 3) as   well as baseline plasma protein and metastatic tumour gene signatures. This way both static and dynamic   expression profiles can be investigated, baseline predictive signatures can be refined and compensatory   activation of pathways revealed  

SMC people involved in the project:

• Bart De Moor (Co-promoter)
• E. Van Cutsem (Co-promoter)
• Sabine Tejpar (Promoter)