Clinical trial NCT01754272: A Non-Interventional Follow-Up to the VELOUR Study - Translational Research
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
mCRC
Aflibercept
FOLFIRI
translational research
retrospective
noninterventional
biomarkers
angiogenesis
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2012-12-21
Enrollment: 1226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastaic colorectal cancer who were refractory to an oxaliplatin-based chemotherapy.

Brief summary: This is a follow-on study to the VELOUR trial (NCT00561470). The aim of this study is to acquire the archived colorectal cancer and metastasized tissue tumour blocks of patients who have participated in the VELOUR study.

These samples will be analysed to find proteins or markers which represent how an individual may be responding to treatment. The identification of these markers may help provide personalised and more effective treatment programs for patients with similar conditions in the future.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients who have participated in the VELOUR trial

Exclusion Criteria:

* Patients who have not participated in the VELOUR trial

Primary outcomes:
measure: Primary colorectal cancer tumor blocks
timeFrame: Two years
Secondary outcomes:
measure: Metastatic tumor blocks
timeFrame: Two years
Other outcomes:
measure: Residual blood samples
timeFrame: Two years
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Leuven
country: Belgium
facility: UZ Leuven UZ Gasthuisberg 3000 Leuven
city: Sao Paulo
country: Brazil
facility: Hospital Sírio E Libanês
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Tartu
country: Estonia
facility: SA Põhja Eesti
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Heraklion, Crete
country: Greece
facility: University Hospital Of Heraklion Voutes
city: Milano
country: Italy
facility: IRCCS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center Hematology and Oncology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Sittard-Geleen
country: Netherlands
facility: Orbis Medisch Centrum
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF
city: Cluj Napoca
country: Romania
facility: Spitalul Universitar CF
city: Moscow
country: Russian Federation
facility: NN Blokhin Russian Cancer Research Center
city: Parktown
country: South Africa
facility: Donald Gordon Medical Centre Wits University
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset Onkologiska Kliniken
city: Greater London
country: United Kingdom
facility: Mount Vernon Hospital
Study officials:
affiliation: KU Leuven
name: Sabine Tejpar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: