Background: 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 in 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, which is currently in progress across a number of centres in Australia, 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.
Design: ASCENT is an open-label, prospective, single arm, phase-IV, multi-centre study. The planned 150 patients will be recruited from 17 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until 1st disease progression; and Phase B: FOLFIRI plus bevacizumab administered from 1st disease progression until 2nd disease progression. The primary analysis will test the association between NLR (< 5 versus > 5) 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). Recruitment started in June 2012 and will end after 24 months or when 150 patients are recruited, whichever occurs first.
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: This trial is registered with Clinicaltrials.gov, registration number NCT01588990 (ML25753).