Trial Information

A Non-Interventional Follow-Up to the VELOUR Study (Multicentre International Study of Aflibercept Versus Placebo in Combination With FOLFIRI for Metastatic Colorectal Cancer) - Translational Research

The VELOUR trial (NCT00561470) has demonstrated the efficacy of aflibercept as a second line
treatment in combination with fluorouracil, leucovorin, irinotecan (FOLFIRI)for metastatic
colorectal cancer (mCRC) patients refractory to a first line oxaliplatin based chemotherapy
regimen (Van Cutsem E., JCO 30 (2012):pp3499-3506). The FDA has approved Aflibercept
(Zaltrap) for the treatment of metastatic colorectal cancer in combination with FOLFIRI on
August 3rd 2012 and by European Medical Agency (EMEA) on November 15th 2012.

While the VELOUR study confirmed the benefits of using aflibercept in combination with
FOLFIRI, the availability of biomarkers accurately predicting patients responding to this
combination would further improve clinical utility of this drug. The molecular profiling of
the Formaldehyde fixed paraffin embedded (FFPE) clinical tumor samples and serial plasma
samples obtained from patients involved in VELOUR study and subsequent analysis of the
molecular and clinical data would provide an invaluable opportunity to discover and
potentially validate such biomarkers.

As blocks were not collected as part of the VELOUR trial, this protocol deals primarily with
the steps that will be taken to gain ethics and consent in each of the participating
countries and how the blocks will then be sourced and acquired, finally deposited in a
biobank situated in KULeuven.

A VELOUR Translational Research Consortium (VTRC) has been formed by the Catholic University
of Leuven (KULeuven)and Almac Diagnostics for the realisation of this study. The number of
blocks available based on the surgical list held for the trial is estimated at 1030 (84% of
complete trial cohort) and from a profiling viewpoint it has been calculated that the
minimum number of blocks acceptable for processing and biomarker identification / validation
is 500.

Due to the specific interest in angiogenesis, the VTRC consortium will aim to source blocks
with both tumor and surrounding stromal tissue which will then be macro-dissected with the
aim to generate data for both the tumor and surrounding angiogenic stroma. The project will
generate gene expression, immunohistochemistry (IHC) and mutational data for these samples.
In addition single nucleotide polymorphisms (SNP) data will be generated from non-tumor
tissue, focusing on polymorphisms that demonstrate an association with disease or response
outcome to therapy. Pre-processing and in silico evaluation of all data generated will
support the outcome objectives of this study.