Condition category
Cancer
Date applied
20/06/2008
Date assigned
29/08/2008
Last edited
17/03/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Ricky Sharma

ORCID ID

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)
Headington
Oxford
OX3 7DQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

OCTO_009

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

Acronym

FOXFIRE

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.

On 17/03/2015 the overall trial end date was changed from 01/12/2014 to 31/10/2016.

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Colorectal cancer with liver only or liver dominant metastases

Intervention

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

Drug

Phase

Phase III

Drug names

5-fluorouracil, oxaliplatin, folinic acid

Primary outcome measures

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

01/11/2008

Overall trial end date

31/10/2016

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

490

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 breast-feeding
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

01/11/2008

Recruitment end date

01/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Oncology Clinical Trials Office (OCTO)
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

University of Oxford Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom
-
heather.house@admin.ox.ac.uk

Sponsor type

University/education

Website

http://www.ox.ac.uk

Funders

Funder type

Charity

Funder name

FOXFIRE is an independent, investigator-led trial funded by The Bobby Moore Fund for Cancer Research UK along with an educational grant provided by Sirtex Technology. The device manufacturer, Sirtex Medical Ltd, is providing SIR-Spheres® for the study free of charge.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25011439

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