A prospective randomised open label trial of oxaliplatin/fluoropyrimidine versus oxaliplatin/fluoropyrimidine plus cetuximab pre- and post-operatively in patients with resectable colorectal liver metastasis requiring chemotherapy

ISRCTN	ISRCTN22944367
DOI	https://doi.org/10.1186/ISRCTN22944367
ClinicalTrials.gov (NCT)	NCT00482222
Clinical Trials Information System (CTIS)	2006-003121-82
Protocol serial number	UOS ref: 4351
Sponsor	University Hospital Southampton NHS Foundation Trust (UK)
Funder	Cancer Research UK (UK)

Submission date: 07/06/2006
Registration date: 21/07/2006
Last edited: 21/07/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-chemotherapy-with-or-without-cetuximab-for-bowel-cancer-that-has-spread-to-the-liver-but-can-be-removed-surgically-new-epoc

Contact information

Prof John Primrose
Scientific

University Surgical Unit MP816
F Level Centre Block
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Phone	+44 (0)23 8079 6144
Email	j.n.primrose@soton.ac.uk

Study information

Primary study design	Interventional
Study design	An open label randomized controlled trial
Secondary study design	Randomised controlled trial
Scientific title	A prospective randomised open label trial of oxaliplatin/fluoropyrimidine versus oxaliplatin/fluoropyrimidine plus cetuximab pre- and post-operatively in patients with resectable colorectal liver metastasis requiring chemotherapy
Study acronym	New EPOC
Study objectives	To determine whether the addition of an epidermal growth factor receptor (EGFR) antibody to an oxaliplatin/fluoropyrimidine regimen improves progression-free survival in patients with resectable liver metastasis from colorectal cancer undergoing liver resection. On 04/05/2007 the target number of participants was changed from 330 to 340. On 08/08/2008 the including and exclusion criteria were updated. The sponsor address was also updated. Details of all changes can be found in the relevant fields. On 30/10/2013 the following changes were made to the trial record: 1. The anticipated end date was changed from 31/08/2011 to 01/05/2018. The trial is now closed to recruitment and patients are in follow-up for 5 years. 2. The target number of participants was changed from 340 to 288. Details of other changes can be found in the relevant fields.
Ethics approval(s)	This study was given a favourable ethical opinion on 01/12/2006
Health condition(s) or problem(s) studied	Colorectal cancer with liver metastases
Intervention	Experimental arm: Oxaliplatin/fluoropyrimidine/anti-EGFR antibody for three months. Surgical resection when fit following chemotherapy, usually 3-4 weeks. Three additional months of chemotherapy when fit following surgery, usually after one month. Control arm: Oxaliplatin/fluoropyrimidine for three months. Surgical resection when fit following chemotherapy. Three additional months of chemotherapy when fit following surgery. As of 04/05/2007 the anticipated start and end dates have been updated to: Anticipated start date: the study opened to recruitment on 5th February 2007 Anticipated end date: December 2014 The previous sponsor for this trial (up to 04/05/2007) was: University of Southampton (UK) Research Governance Office Legal Services Room 4033, Building 37 University Road Southampton SO17 1BJ United Kingdom Between 04/05/2007 and 08/08/2008, the sponsor address was: Southampton University Hospitals NHS Trust (UK) Research and Development Trust Management Offices, MP18 Southampton General Hospital Southampton SO16 6YD United Kingdom The current address can be found in the sponsor section below.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Oxaliplatin, fluoropyrimidine, cetuximab
Primary outcome measure(s)	Progression-free survival
Key secondary outcome measure(s)	Current secondary outcome measures as of 30/10/2013: 1. Toxicity 2. Overall survival Previous secondary outcome measures: 1. Quality of life 2. Toxicity 3. Overall survival 4. Cost effectiveness
Completion date	01/05/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	288
Total final enrolment	257
Key inclusion criteria	Current inclusion criteria as of 08/08/2008: 1. Confirmed colorectal adenocarcinoma: either previous or current histologically or radiologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of advanced and/or metastatic disease; confirmed primary adenocarcinoma of colon or rectum 2. Presence of potentially resectable colorectal cancer liver metastases 3. Patients who are thought by the surgeon to be suboptimally resectable are included 4. No previous systemic chemotherapy for metastatic disease 5. World Health Organization (WHO) performance status 0, 1 or 2 Added as of 04/05/2007: 6. Baseline laboratory tests (refer to the protocol for full description) 7. All patients must be aged 18 years or older 8. Negative pregnancy test for women of childbearing potential, adequate contraception for men and women 9. Written informed consent 10. Consent to allow surplus pathological material to be analysed for translational research projects (patients may decline participation in this supplementary study and still participate in the main trial) Previous inclusion criteria: 1. Confirmed colorectal adenocarcinoma: either previous or current histologically or radiologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of advanced and/or metastatic disease; confirmed primary adenocarcinoma of colon or rectum 2. Presence of potential colorectal cancer resectable liver metastases 3. Patients who are thought by the surgeon to be suboptimally resectable are included 4. No previous systemic chemotherapy for metastatic disease 5. World Health Organization (WHO) performance status 0, 1 or 2 Added as of 04/05/2007: 6. Baseline laboratory tests (refer to the protocol for full description) 7. All patients must be aged 18 years or older 8. Negative pregnancy test for women of childbearing potential, adequate contraception for men and women 9. Written informed consent 10. Consent to allow surplus pathological material to be analysed for translational research projects (patients may decline participation in this supplementary study and still participate in the main trial)
Key exclusion criteria	Patients who are unfit for the chemotherapy regimens in the protocol e.g.: 1. Patients with severe uncontrolled concurrent medical illness 2. Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or comply with oral medication 3. Partial or complete bowel obstruction 4. Pre-existing neuropathy (> grade 1) 5. Patients requiring ongoing treatment with a contraindicated concomitant medication 6. Patients with a previous or current malignant disease which in the judgement of the treating investigator, is likely to interfere with this study treatment or assessment of response Added as of 04/05/2007: 7. Patients with known hypersensitivity reactions to any of the components of the study treatments 8. Patients with brain metastases 9. Female patients who are lactating Added as of 08/08/2008: 10. Patients who have received prior chemotherapy with oxaliplatin 11. Patients with a personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency 12. Patients who possess the KRAS mutant genotype or whose KRAS genotype status is unknown in the primary tumour
Date of first enrolment	01/08/2006
Date of final enrolment	01/05/2018

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University Surgical Unit MP816

Southampton
SO16 6YD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/05/2014	11/04/2019	Yes	No
Results article	results	09/08/2016	11/04/2019	Yes	No
Results article	results	27/09/2017	11/04/2019	Yes	No
Results article	results	01/03/2020	06/02/2020	Yes	No
Other publications	Secondary analysis	20/07/2023	21/07/2023	Yes	No
Plain English results				No	Yes

Editorial Notes

21/07/2023: Publication reference added.
22/07/2020: Cancer Research UK lay results summary link added to Results (plain English).
19/03/2020: EudraCT number added.
06/02/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
11/04/2019: Publication reference added.