CLOCC TRIAL

1
CLOCC TRIAL A Phase III study of the local
treatment of colorectal liver metastases by
radiofrequency ablation and chemotherapy versus
chemotherapy alone
An EORTC Trial being run in the UK by the NCRI
Colorectal Cancer Sub-Group EORTC Principal
Investigator Dr Theo Ruers UK Co-Investigators
Jonathan Ledermann Graeme Poston
RATIONALE
Liver is the common site of relapse in patients
with colorectal cancer. Chemotherapy is the
treatment of choice for patients where surgical
removal of lesions is not possible. The outcome
for patients with unresectable liver metastases
treated with chemotherapy is poor 5yr. Survival
of ? 1 and median survival ? 1 year. Tumour
destruction using radiofrequency may offer an
improvement in outcome. The purpose of this trial
is to treat patients who have inoperable
metastases with chemotherapy or RFA and
chemotherapy. The chemotherapy schedule used
will be a combination of 5FU, leucovorin and
oxaliplatin.
Trial design
Objectives
Radiofrequency

• Primary
• To determine whether radiofrequency in
  combination with chemotherapy leads to superior
  overall survival compared to chemotherapy alone.
• Secondary
• Progression free survival
• QOL
• Health economics

• Tumour ablative technique which can be combined
  with surgery
• Imaging of procedure by ultrasound
• During radiofrequency thermal heat injury leads
  to tissue coagulation
• Effective in the local destruction of liver
  metastases
• Suitable for lesions which are not totally
  resectable due to number or location and close to
  large blood vessels

Radiofrequency
Chemotherapy
Statistics

• Schedule 2
• - Oxaliplatin/5FU/LV
• Ox 85mg/m2 day 1 only
• LV 175mg/m2 day 1 only
• 5FU 400mg/m2 bolus
• 5FR 2400mg/m2 46h iv infusion
• - 2 weekly for 6 months ie. 12 courses

• Performed either during open surgery or
  percutaneously
• Radiofrequency zone to include tumour and 1 cm
  of normal tissue
• RITA, TYCO or Boston Scientific probes supplied
• Central QA performed on all patients

• Sample size 142 patients (UK - 1/3)
• 37 difference in median survival 17 to 23.3
  months
• 80 power 5 significance

Pre-treatment assessments
Eligibility criteria
Exclusion criteria

• Progression free survival
• -CT scans after cycle 3, 6, 9 12
• - chest x-ray
• Follow up 3 monthly up to year 2 then 6
  monthly
• QOL 6, 12, 18 24 weeks post chemo and in Arm
  1, 1 week after RF treatment
• Health economics

• Resection of primary tumour
• Unresectable liver metastases
• No extrahepatic disease
• Total number of metastatic deposits ?10
• Max. diameter of lesions 4cm
• Patient consent
• 18 - 80 years
• Normal haematology biochemistry

• WHO status of ? 1
• Hepatic sufficiency (BR, Alk ?3xULN
• Peripheral neuropathy CTC grade ? 1
• Uncontrolled congestive heart failure, angina
  pectoris, hypertension or arrythmia
• Any contraindication to the use of
  5FU/LV/Oxaliplatin
• Active infection
• Pregnant or lactating women

Response and assessments
Radiofrequency Centres
Current Status

• Progression free survival
• - CT scans and/or USS after cycle 3, 6, 9 12
• - chest x-ray
• Follow up 3 monthly up to year 2 then 6
  monthly
• QOL 6, 12, 18 24 weeks post chemo and in Arm
  1, 1 week after RF treatment
• Health economics

• 21 UK centres have LREC approval
• Current accrual overall is 73
• 6 patients have been entered in the UK
• Expected closure date 30.09.07
• The protocol has been amended to a Phase II
  trial and we are awaiting MREC approval.

Manchester
Liverpool
Leicester
Birmingham
Oxford
Bristol
London UCL
Southampton
Cancer Research UK UCL Cancer Trials
Centre contact Sara Okumu-Fransche 020 7679 8095,
s.okumu-fransche_at_ctc.ucl.ac.uk
September 2005