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Open Access Highly Accessed Study protocol

FOXFIRE protocol: an open-label, randomised, phase III trial of 5-fluorouracil, oxaliplatin and folinic acid (OxMdG) with or without interventional Selective Internal Radiation Therapy (SIRT) as first-line treatment for patients with unresectable liver-only or liver-dominant metastatic colorectal cancer

Susan J Dutton1, Nicola Kenealy2, Sharon B Love1, Harpreet S Wasan3, Ricky A Sharma4* and on behalf of the FOXFIRE Protocol Development Group and the NCRI Colorectal Clinical Study Group

Author Affiliations

1 Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

2 Oncology Clinical Trials Office, Department of Oncology, University of Oxford, Oxford, UK

3 Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK

4 CRUK-MRC Oxford Institute for Radiation Oncology, NIHR Biomedical Research Centre Oxford, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, UK

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BMC Cancer 2014, 14:497  doi:10.1186/1471-2407-14-497

Published: 9 July 2014

Abstract

Background

Colorectal cancer (CRC) is the second most common malignancy in Europe and a leading cause of cancer-related death. Almost 50% of patients with CRC develop liver metastases, which heralds a poor prognosis unless metastases can be downsized to surgical resection or ablation. The FOXFIRE trial examines the hypothesis that combining radiosensitising chemotherapy (OxMdG: oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-Spheres®; Sirtex Medical Limited, North Sydney, Australia) as a first-line treatment for liver-dominant metastatic CRC will improve clinical outcomes when compared to OxMdG chemotherapy alone.

Methods/Design

FOXFIRE is an open-label, multicentre, randomised controlled trial of OxMdG with or without the addition of SIRT (1:1 randomisation). Eligible adult patients have histologically confirmed colorectal adenocarcinoma, liver metastases measurable on computed tomography scan and untreatable by either surgical resection or local ablation, and they may have limited extra-hepatic disease, defined as ≤5 nodules in the lung and/or one other metastatic site which is amenable to future definitive treatment. Eligible patients may have received adjuvant chemotherapy following resection of the primary tumour, but are not permitted to have previously received chemotherapy for metastatic disease, and must have a life expectancy of ≥3 months and a WHO performance status of 0–1. The primary outcome is overall survival. Secondary outcomes include progression free survival (PFS), liver-specific PFS, patient-reported outcomes, safety, response rate, resection rate and cost-effectiveness. FOXFIRE shares a combined statistical analysis plan with an international sister trial called SIRFLOX.

Discussion

This trial is establishing a network of SIRT centres and ‘feeder’ chemotherapy-only centres to standardise the delivery of SIRT across the whole of the UK and to provide greater equity of access to this highly specialised liver-directed therapy. The FOXFIRE trial will establish the potential role of adding SIRT to first-line chemotherapy for unresectable liver metastatic colorectal cancer, and the impact on current treatment paradigms for metastatic CRC.

Trial registration

ISRCTN83867919

Keywords:
Colorectal cancer; Liver metastases; Selective Internal Radiation Therapy (SIRT); Radio-embolization; Brachytherapy; Radiosensitisation; Radiosensitization; Quality of life; Health economics