ATTACHE: A Trial in the Timing of Surgery and Adjuvant Chemotherapy for Hepatic Metastases from Colorectal Cancer.

Interventions: Chemoptherapy agents used in this trial will be mFOLFOX6, XELOX or FOLFIRI. mFOLFOX6 is the combination of Oxaliplatin, Leucovorin and Fluorouracil as set out below. XELOX is the combination of Oxaliplatin and Capecitabine set out below. FOLFIRI is the combination of Irinotecan, Leucovorin and Fluorouracil as set out below. There are two different treatment options mFOLFOX6 or XELOX which will be determined by the treating investigator prior to randomisaiotn. Patients are not permitted to change treatments during the trial. Preoperatively: mFOLFOX6 Every 2 weeks for 6 cycles: Oxaliplatin 85mg/m2 by intravenous infusion over 2 hours on day 1. Leucovorin 400mg/m2 by intravenous infusion over 1 to 2 minutes on days 1 and 2 Fluorouracil 400mg/m2 by intravenous infusion over 3 to 5 minutes on day 1 Fluorouracil 2400mg/m2 as a continuous intravenous infusion over 46 hours (Day 1 and 2) equivalent to 1200mg/m2/day.
OR
XELOX Every 3 weeks for 4 cycles: Oxaliplatin 130mg/m2 by intravenous infusion over 2 hours on day 1 Capecitabine 1000mg/m2 oral tablet twice daily on days 1-14.
Followed by Surgery: Surgical resection of liver metastases will be carried out, at the earliest 4 weeks and at the latest 8 weeks after completion of cycle 6 mFOLFOX6 or cycle 4 XELOX. Patients must have recovered from side effects and liver function must be adequate for liver surgery as per local hospital guidelines.
Post-operatively: Chemotherapy should not be administered until at least 4 weeks after surgery. This must not be started after surgery unless the liver, renal and haematological functions are within the same limits determined for the introduction of pre-operative chemotherapy. In the event of a surgical complication a delay of up to 12 weeks is acceptable before the
Primary outcome(s): Determine the differences in peri-operative morbidity between groups?
Tools and tests used to gather this information will include, post operative follow up and reports of serious complications, blood tests, physical exams, World Health Organisation (WHO) performance status, urinanalysis, Carcinoembryonic Antigen tumour marker, (CEA), toxicity, adverse events Computed Tomography Scan (CT scan) of chest, abdomen and pelvis.[These assessments will be made pre and post surgery. Post surgery CT scans of chest, abdomen and pelvis to be performed within 30 days of surgery.]
Study Design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety/efficacy