Randomised phase III study of the local treatment of liver metastases by radiofrequency combined with chemotherapy versus chemotherapy alone in patients with unresectable colorectal liver metastases

ISRCTN	ISRCTN58458258
DOI	https://doi.org/10.1186/ISRCTN58458258
ClinicalTrials.gov number	NCT00043004
Secondary identifying numbers	EORTC 40004

Submission date: 04/06/2003
Registration date: 23/07/2003
Last edited: 23/04/2021

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Wendy Wood
Scientific

CR UK and UCL Cancer Trials Centre
90 Tottenham Court Road
London
London
W1T 4TJ
United Kingdom

Phone	+44 (0)20 7679 9858
Email	W.Wood@CTC.UCL.AC.UK

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Randomised phase III study of the local treatment of liver metastases by radiofrequency combined with chemotherapy versus chemotherapy alone in patients with unresectable colorectal liver metastases
Study acronym	CLOCC
Study objectives	The 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; five year survival of less than 1% and median survival less than one year. Tumour destruction using radio frequency may offer an improvement in outcome. The purpose of this trial is to treat patients who have inoperable metastases with chemotherapy or RadioFrequency Ablation (RFA) and chemotherapy. The chemotherapy schedule used will be a combination of 5-Fluorouracil (5FU), leucovorin and oxaliplatin.
Ethics approval(s)	LREC approval for UK sites
Health condition(s) or problem(s) studied	Liver metastases in colorectal cancer
Intervention	Arm one: Radiofrequency ablation and chemotherapy Arm two: Chemotherapy alone. Radiofrequency: 1. Tumour ablative technique which can be combined with surgery 2. Imaging of procedure by ultrasound 3. During radiofrequency thermal heat injury leads to tissue coagulation 4. Effective in the local destruction of liver metastases 5. Suitable for lesions which are not totally resectable due to number or location and close to large blood vessels Chemotherapy: 1. Oxaliplatin 85mg/m^2 day one only 2. Leucovorin 175mg/m^2 day one only 3. 5-Fluorouracil 400mg/m^2 bolus 4. 5FU 2400mg/m^2 at 46 hours intravenous infusion 5. Fortnightly for six months i.e. 12 courses
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	5-Fluorouracil (5FU), LeucoVorin (LV) and oxaliplatin.
Primary outcome measure	To determine whether radiofrequency in combination with chemotherapy leads to superior overall survival compared to chemotherapy alone.
Secondary outcome measures	1. Progression free survival 2. Quality of Life 3. Health economics
Overall study start date	01/04/2003
Completion date	30/09/2007
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	142
Total final enrolment	119
Key inclusion criteria	Patients with unresectable colorectal liver metastases: 1. Resection of primary tumour 2. Unresectable liver metastases 3. No extrahepatic disease 4. Total number of metastatic deposits less than ten 5. Maximum diameter of lesions 4cm 6. Patient consent 7. Aged 18 to 80 years 8. Normal haematology and biochemistry
Key exclusion criteria	1. World Health Organisation (WHO) status of more than or equal to one 2. Hepatic sufficiency (Bilirubin, Alkaline Phosphatase more than three times the Upper Limit of Normal [ULN]) 3. Peripheral neuropathy Common Toxicity Criteria (CTC) grade more than or equal to one 4. Uncontrolled congestive heart failure, angina pectoris, hypertension or arrythmia 5. Any contraindication to the use of 5FU/LV/Oxaliplatin 6. Active infection 7. Pregnant or lactating women
Date of first enrolment	01/04/2003
Date of final enrolment	30/09/2007

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

CR UK and UCL Cancer Trials Centre

London
W1T 4TJ
United Kingdom

Sponsor information

Cancer Research UK
Charity

PO Box 123
61 Lincoln's Inn Fields
London
WC2A 3PX
United Kingdom

Phone	+44 (0)20 7317 5186
Email	kate.law@cancer.org.uk
"ROR"	https://ror.org/054225q67

Funders

Funder type

Charity

Cancer Research UK (ref: C8374/A3488)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results			No	No
Plain English results			No	Yes
Abstract results	20/05/2008	23/04/2021	No	No
Results article	01/10/2012	23/04/2021	Yes	No

Editorial Notes

23/04/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)