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

Phase 3

Completed

• Conditions: Colorectal cancer with liver only or liver dominant metastases; Cancer; Malignant neoplasm of colon

• Registration Number: ISRCTN83867919
• Lead Sponsor: niversity of Oxford (UK)

Brief Summary

2014 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/25011439 protocol 2017 Results article in http://www.ncbi.nlm.nih.gov/pubmed/28781171 results

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-08-29
• Study Completion: 2016-10-31
• Last Update Posted: 7 November 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 549

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

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])

Study & Design

• Study Type: Interventional
• Study Design: Not specified