Open Access Study protocol

An Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™) [ASCENT]

Stephen Clarke1*, Matt Burge2, Cassandra Cordwell3, Peter Gibbs4, William Reece5 and Niall Tebbutt6

Author Affiliations

1 Royal North Shore Hospital, St Leonards, NSW 2065, Australia

2 Royal Brisbane and Women Hospital, Butterfield, QLD, Australia

3 Roche Products, Pty. Limited (Australia), Dee Why, NSW, Australia

4 Royal Melbourne Hospital, Parkville, VIC, Australia

5 Covance Pty Ltd, Sydney, NSW, Australia

6 Austin Health, Heidelberg, VIC, Australia

For all author emails, please log on.

BMC Cancer 2013, 13:120  doi:10.1186/1471-2407-13-120

Published: 15 March 2013

Abstract

Background

The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a well-established first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). However, there remains a need for reproducible, validated, inexpensive and accessible prognostic markers to aid treatment selection. The optimal treatment duration and the role of bevacizumab in certain patient subgroups, considered at particular risk of bevacizumab-mediated toxicity, also require further investigation. The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment.

Methods/design

This open-label, prospective, single arm, phase IV, Australian multi-centre study evaluates the relationship between the host inflammatory response as measured by NLR and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. 150 patients will be recruited from 16 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; and Phase B: FOLFIRI plus bevacizumab administered from first disease progression until second disease progression. The primary analysis will test the association between NLR and progression free survival using a proportional Hazards Model. Secondary analyses will investigate whether the relationship can be improved upon with other prognostic biomarkers, and further characterise the safety of bevacizumab following treatment initiation, and when continued after progression in combination with standard chemotherapy regimens (presented through summary statistics and Kaplan Meier curves).

Discussion

Quantifying the relationship between NLR and PFS will inform decision making on the extent to which this simple metric may be applied clinically.

Trial registration

ClinicalTrials.gov: NCT01588990

Keywords:
Colorectal cancer; Bevacizumab; Treatment beyond progression; Biomarkers; Inflammation