Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Dr Ricky Sharma


Contact details

Oncology Clinical Trials Office (OCTO)
Department of Clinical Pharmacology
Old Road Campus Research Building
University of Oxford
Old Road Campus (off Roosevelt Drive)
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

FOXFIRE: an open-label randomised phase III trial of 5-Fluorouracil, OXaliplatin and Folinic acid +/- Interventional Radio-Embolisation as first line treatment for patients with unresectable liver-only or liver-predominant metastatic colorectal cancer



Study hypothesis

Combination of chemotherapy and radioembolisation will improve the outcome for patients with colorectal cancer plus liver only/ dominant metastases compared with chemotherapy alone.

Ethics approval

The Berkshire Regional Ethics Committee (REC), 16/03/2009, ref: 09/H0505/1

Study design

Open-label multicentre randomised controlled phase III study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Colorectal cancer with liver only or liver dominant metastases


Arm A: Systemic OxMdG chemotherapy: oxaliplatin, folinic acid (FA) and 5-fluorouracil (5-FU)
Arm B: SIR-Spheres® radioembolisation (RE) plus systemic OxMdG chemotherapy: oxaliplatin, FA and 5-FU

Therapy schedule: 14 days per cycle, 12 cycles maximum. Radioembolisation occurs on Day 3 of the 2nd cycle.

The total duration of follow-up is 24 months. After this period, only mortality will be recorded.

Intervention type



Phase III

Drug names

5-fluorouracil, oxaliplatin, folinic acid

Primary outcome measure

Overall survival (OS)

Secondary outcome measures

1. Progression free survival (PFS)
2. Liver-specific PFS
3. Safety and toxicity
4. Healthcare costs/health economics
5. Quality of life, assessed with the euroqol EQ-5D questionnaire at baseline, start of cycle 4 and cycle 12, month 24 and 36, and at progression
6. Response rate
7. Resection rate
8. Percentage of patients receiving second line treatment
9. Interval from randomisation to start of second line treatment

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Histologically confirmed colorectal cancer with liver-only or liver-dominant (see also 'limited and/or resectable extra-hepatic disease' criterion below) metastases not amenable to curative (R0) liver surgical resection (see also exclusion criteria below), which must be agreed at local multi-disciplinary team (MDT) meeting with hepatic surgery & radiology representation.
2. Unequivocal and measurable CT evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of trial entry
3. Both males and females, age >18 years
4. WHO performance status of 0-1
5. Life expectancy >3 months
6. Eligible for systemic chemotherapy as first-line treatment for metastatic colorectal cancer
7. Adequate haematological, renal and hepatic function (recorded within 29 days of randomisation) as follows:
7.1. Serum creatinine <=1.5 x ULN
7.2. Serum bilirubin <=1 x ULN
7.3. Absolute neutrophil count >1.5 x 10^9/L
7.4. Platelets >100 x 10^9/L
7.5. Albumin >=30 g/L
8. Limited and/or resectable extra-hepatic disease (EHD) defined as**:
8.1. Lung lesions (<=5 metastases of <=1 cm each which are immediately amenable to surgery or ablation, without requiring initial chemotherapy for downstaging)
8.2. Positron emission tomography (PET) or biopsy negative lesions (optional if performed)
8.3. Abdominal or perihepatic lymph nodes less than 2 cm in longest diameter
8.4. Presence of detectable extra-hepatic tumour that can be resected. This includes asymptomatic synchronous primary colorectal tumours (i.e. with unresectable liver metastases)
** These criteria will generally be considered mutually exclusive and patients with more than one criterion must be discussed with the TMG
9. Suitable for all aspects of treatment determined by clinical assessment undertaken by the Investigator
10. Female patients must either be post-menopausal or, if pre-menopausal and sexually active, using an acceptable method of contraception
11. Male patients, if sexually active with a pre-menopausal partner, must be using an appropriate method of contraception
12. Willing and able to provide written informed consent

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Liver metastases amenable to curative resection at the time of study entry, unless the patient has limited EHD as defined above
2. Pregnancy or breastfeeding
3. Evidence of ascites, cirrhosis or portal hypertension (as determined by clinical or radiological assessment)
4. Tumour involvement of, or thrombosis leading to complete occlusion of, the main portal vein is an absolute contra-indication to trial entry. Previous liver resection(s) or previous portal vein embolisation are not exclusion criteria to entry into the clinical trial. Patients with complicated surgical histories involving embolisation and resection should be discussed with the TMG prior to study entry for clarification of safety and eligibility.
5. Previous radiotherapy to the upper abdomen or upper lumbar spine
6. Other active malignancy within the past 5 years, excluding colorectal cancer and non-melanoma skin cancers
7. Non-malignant disease that would render the patient ineligible for treatment at the discretion of the investigator
8. Equivocal, immeasurable, or unevaluable metastases in the liver
9. Patients with unequivocal evidence of bone metastasis are not permitted to enter the trial. Patients with a single equivocal lesion of uncertain significance should be discussed with the FOXFIRE Trial Office.
10. Dose limiting toxicity associated with previous 5-FU or oxaliplatin chemotherapy.
11. Previous chemotherapy for metastatic colorectal cancer. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that the last dose of adjuvant chemotherapy was completed at least 6 months prior to entry into this study. Patients who have previously received oxaliplatin-based adjuvant chemotherapy regimens should be discussed with the FOXFIRE Trial Office
12. Peripheral neuropathy on clinical examination >grade 1 (National Cancer Institute Common Toxicity Criteria [NCI-CTC v.3])

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Oncology Clinical Trials Office (OCTO)
United Kingdom

Sponsor information


University of Oxford (UK)

Sponsor details

University of Oxford Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Old Road
United Kingdom

Sponsor type




Funder type


Funder name

Bobby Moore Fund for Cancer Research UK

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Sirtex (educational grant, providing SIR-Spheres® for the study free of charge)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from the FOXFIRE trial team: Ricky Sharma ( and the trial management team ( All requests will be considered on an individual basis and in accordance with a data sharing agreement.

Intention to publish date


Participant level data

Available on request

Basic results (scientific)

See additional file ISRCTN83867919_BasicResults_13Sep2017.pdf

Publication list

2014 protocol in:
2017 results in:

Publication citations

  1. Protocol

    Dutton SJ, Kenealy N, Love SB, Wasan HS, Sharma RA, , 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., BMC Cancer, 2014, 14, 497, doi: 10.1186/1471-2407-14-497.

Additional files

Editorial Notes

30/05/2018: IPD sharing statement added. 14/05/2018: Publication reference added. The basic results of this trial have been uploaded as an additional file. Please note that the secondary outcomes quality of life and health economics/cost effectiveness analysis are currently being analysed. 09/08/2017: Recruitment dates, publication and dissemination plan and IPD sharing statement added. 17/03/2015: The overall trial end date was changed from 01/12/2014 to 31/10/2016.