Additional identifiers
EudraCT/CTIS number
IRAS 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.
Ethics approval(s)
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
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details 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
Pharmaceutical study type(s)
Phase
Phase III
Drug/device/biological/vaccine name(s)
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 study start date
01/11/2008
Overall study end date
31/10/2016
Reason abandoned (if study stopped)
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(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
490
Total final enrolment
549
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
13/11/2009
Recruitment end date
31/10/2014
Locations
Countries of recruitment
England, United Kingdom
Study 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
England
United Kingdom
-
heather.house@admin.ox.ac.uk
Sponsor type
University/education
Website
ROR
Funders
Funder type
Charity
Funder name
Bobby Moore Fund for Cancer Research UK
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sirtex (educational grant, 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
Planned publication in a high-impact peer reviewed journal.
Intention to publish date
01/09/2017
Individual participant data (IPD) sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request from the FOXFIRE trial team: Ricky Sharma (ricky.sharma@oncology.ox.ac.uk) and the trial management team (octo-foxfire@oncology.ox.ac.uk). All requests will be considered on an individual basis and in accordance with a data sharing agreement.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 09/07/2014 | Yes | No | |
| Results article | results | 01/09/2017 | Yes | No | |
| Basic results | 13/09/2017 | 14/05/2018 | No | No | |
| Plain English results | 26/10/2022 | No | Yes |
Additional files
- ISRCTN83867919_BasicResults_13Sep2017.pdf Uploaded 14/05/2018