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Colorectal CancerPhase 3NCT00182715

Combination Chemotherapy With or Without Cetuximab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

A Phase 3 study testing cetuximab, capecitabine and fluorouracil in people with Colorectal Cancer, run by Velindre NHS Trust at 82 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
cetuximab, capecitabine and fluorouracil
How many people
2,421 participants
Where
82 sitesin 2 countries
Study dates
Mar 2005to May 2009
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of colorectal adenocarcinoma, defined by 1 of the following:
  • Histologically confirmed primary adenocarcinoma of the colon or rectum with clinical or radiological evidence of advanced and/or metastatic disease
  • Histologically or cytologically confirmed metastatic adenocarcinoma with clinical or radiological evidence of primary colorectal tumor
  • Unidimensionally measurable disease
  • Inoperable metastatic or locoregional disease
  • Ineligible for hepatic resection after first-line combination chemotherapy
  • No brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.25 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 times ULN
  • AST or ALT ≤ 2.5 times ULN

Renal

  • Creatinine clearance or glomerular filtration rate ≥ 50 mL/min

Cardiovascular

  • No poorly controlled angina
  • No myocardial infarction within the past 3 months

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Must be considered fit to undergo combination chemotherapy
  • No psychiatric or neurological condition that would preclude study compliance or giving informed consent
  • No partial or complete bowel obstruction
  • No other malignant disease that would preclude study treatment
  • No preexisting neuropathy > grade 1
  • No known hypersensitivity reaction to any of the components of study drugs
  • No known DPD deficiency or personal or family history suggestiv of DPD deficiency
  • No other severe uncontrolled medical illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior systemic palliative chemotherapy for metastatic disease
  • No prior oxaliplatin
  • More than 1 month since prior adjuvant fluorouracil (5-FU) (with or without leucovorin calcium), capecitabine, or irinotecan
  • More than 1 month since prior rectal chemoradiotherapy with 5-FU (with or without leucovorin calcium) or capecitabine

Endocrine therapy

  • Not specified

Radiotherapy

  • See Chemotherapy

Surgery

  • Not specified

Other

  • No concurrent brivudine or sorivudine (for patients receiving capecitabine on study)

Trial locations and contacts

82 sites in 2 countries.

82 sites in 2 countries

United Kingdom72 sites

  • Aberdeen Royal Infirmary

    Aberdeen, Scotland, AB25 2ZN

  • North Hampshire Hospital

    Basingstoke, England, RG24 9NA

  • Belfast City Hospital Trust Incorporating Belvoir Park Hospital

    Belfast, Northern Ireland, BT8 8JR

  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

    Birmingham, England, B12 2TH

  • Blackpool Victoria Hospital

    Blackpool, England, FY3 8NR

  • Royal Bournemouth Hospital NHS Trust

    Bournemouth, England, BH7 7DW

  • Bradford Royal Infirmary

    Bradford, England, BD9 6RJ

  • Sussex Cancer Centre at Royal Sussex County Hospital

    Brighton, England, BN2 5BE

  • Bristol Haematology and Oncology Centre

    Bristol, England, BS2 8ED

  • Queen's Hospital

    Burton-on-Trent, England, DE13 0RB

  • West Suffolk Hospital

    Bury St Edmunds, England, IP33 2QZ

  • Addenbrooke's Hospital

    Cambridge, England, CB2 0QQ

  • Velindre Cancer Center at Velindre Hospital

    Cardiff, Wales, CF14 2TL

  • Cumberland Infirmary

    Carlisle, England, CA2 7HY

  • Cheltenham General Hospital

    Cheltenham, England, GL53 7AN

  • Essex County Hospital

    Colchester, England, C03 3NB

  • Derbyshire Royal Infirmary

    Derby, England, DE1 2QY

  • Dorset County Hospital

    Dorchester, England, DT1 2JY

  • Hairmyres Hospital

    East Kilbride, Scotland, G75 8RG

  • Eastbourne District General Hospital

    Eastbourne, England, BN21 2UD

  • Edinburgh Cancer Centre at Western General Hospital

    Edinburgh, Scotland, EH4 2XU

  • Princess Alexandra Hospital

    Essex, England, CM20 1QX

  • St. Luke's Cancer Centre at Royal Surrey County Hospital

    Guildford, England, GU2 7XX

  • Huddersfield Royal Infirmary

    Huddersfield, West Yorks, England, HD3 3EA

  • Princess Royal Hospital at Hull and East Yorkshire NHS Trust

    Hull, England, HU8 9HE

  • Hinchingbrooke Hospital

    Huntingdon, England, PE18 6NT

  • Raigmore Hospital

    Inverness, Scotland, 1V2 3UJ

  • Cookridge Hospital

    Leeds, England, LS16 6QB

  • Aintree University Hospital

    Liverpool, England, L9 7AL

  • Saint Bartholomew's Hospital

    London, England, EC1A 7BE

  • Helen Rollason Cancer Care Centre at North Middlesex Hospital

    London, England, N18 1QX

  • University College of London Hospitals

    London, England, NW1 2PG

  • Royal Free and University College Medical School

    London, England, NW3 2PF

  • Queen Elizabeth Hospital - Woolwich

    London, England, SE18 4QH

  • Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals

    London, England, SE5 9NU

  • St. George's Hospital

    London, England, SW17 0QT

  • Royal Marsden - London

    London, England, SW3 6JJ

  • Hammersmith Hospital

    London, England, W12 OHS

  • St. Mary's Hospital

    London, England, W2 1NY

  • Charing Cross Hospital

    London, England, W6 8RF

  • Southport and Formby District General Hospital

    Merseyside, England, CH63 4JY

  • St. Mary's Hospital

    Newport, England, PO30 5TG

  • North Tyneside Hospital

    North Shields, England, NE29 8NH

  • Northampton General Hospital NHS Trust

    Northampton, England, NN6 8BJ

  • Mount Vernon Cancer Centre at Mount Vernon Hospital

    Northwood, England, HA6 2RN

  • Nottingham City Hospital NHS Trust

    Nottingham, England, NG5 1PB

  • Peterborough Hospitals Trust

    Peterborough, England, PE3 6DA

  • Derriford Hospital

    Plymouth, England, PL6 8DH

  • Poole Hospital NHS Trust

    Poole Dorset, England, BH15 2JB

  • Portsmouth Oncology Centre at Saint Mary's Hospital

    Portsmouth Hants, England, PO3 6AD

  • Whiston Hospital

    Prescot Merseyside, England, L35 5DR

  • Royal Preston Hospital

    Preston, England, PR2 9HT

  • Glan Clwyd Hospital

    Rhyl, Denbighshire, Wales, LL 18 5UJ

  • Conquest Hospital

    Saint Leonards-on-Sea, England, TN37 7RD

  • Salisbury District Hospital

    Salisbury, England, SP2 8BJ

  • Scarborough General Hospital

    Scarborough, England, YO12 6QL

  • South Tyneside District Hospital

    South Shields, England, NE34 0PL

  • Southampton General Hospital

    Southampton, England, SO16 6YD

  • University Hospital of North Staffordshire

    Stoke-on-Trent, England, ST4 7LN

  • Sunderland Royal Hospital

    Sunderland, England, SR4 7TP

  • Royal Marsden - Surrey

    Sutton, England, SM2 5PT

  • South West Wales Cancer Institute

    Swansea, Wales, SA2 8QA

  • Great Western Hospital

    Swindon, England, SN3 6BB

  • Torbay Hospital

    Torquay, England, TQ2 7AA

  • Royal Cornwall Hospital

    Truro, Cornwall, England, TR1 3LJ

  • Walsall Manor Hospital

    Walsall, England, WS2 9PS

  • Good Hope Hospital Trust

    West Midlands, England, B75 7RR

  • Royal Hampshire County Hospital

    Winchester, England, SO22 5DG

  • Worcester Royal Hospital

    Worcester, England, WR5 1DD

  • Worthing Hospital

    Worthing, England, BN11 2DH

  • Wrexham Maelor Hospital

    Wrexham, Wales, LL13 7TD

  • Yeovil District Hospital

    Yeovil, England, BA21 4AT

Other trials in United Kingdom

Ireland10 sites

  • Mercy University Hospital

    Cork

  • Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital

    Dublin, 24

  • St. Vincent's University Hospital

    Dublin, 4

  • Mater Misericordiae University Hospital

    Dublin, 7

  • Mater Private Hospital

    Dublin, 7

  • St. James's Hospital

    Dublin, 8

  • Beaumont Hospital

    Dublin, 9

  • Galway University Hospital

    Galway

  • Mid-Western Cancer Centre at Mid-Western Regional Hospital

    Limerick, 0009

  • Waterford Regional Hospital

    Waterford

Other trials in Ireland

About this study

Official title: A Three-Arm Randomised Controlled Trial Comparing Either Continuous Chemotherapy Plus Cetuximab or Intermittent Chemotherapy With Standard Continuous Palliative Combination Chemotherapy With Oxaliplatin and a Fluoropyrimidine in First Line Treatment of Metastatic Colorectal Cancer (COIN)

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether combination chemotherapy and cetuximab are more effective than combination chemotherapy alone in treating colorectal cancer.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and cetuximab to see how well they work compared to combination chemotherapy alone as first-line therapy in treating patients with metastatic colorectal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Compare the overall survival of patients with metastatic colorectal adenocarcinoma treated with continuous combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) with vs without cetuximab vs intermittent combination chemotherapy with OxMdG or XELOX as first-line therapy.

Secondary

  • Compare time of disease control and progression- and failure-free survival of patients treated with these regimens.
  • Compare response in patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Compare the cost effectiveness of these regimens in these patients.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter, open label, randomized, controlled study. Patients are randomized to 1 of 3 treatment arms.

  • Arm I (continuous chemotherapy): Patients receive 1 of the following combination chemotherapy regimens of their choice (or as per participating center):
  • OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • XELOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm II (continuous chemotherapy and cetuximab): Patients receive OxMdG or XELOX as in arm I. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8 (for patients receiving OxMdG) OR days 1, 8, and 15 (for patients receiving XELOX). Treatment with OxMdG and cetuximab repeats every 14 days in the absence of disease progression or unacceptable toxicity. Treatment with XELOX and cetuximab repeats every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm III (intermittent chemotherapy): Patients receive OxMdG or XELOX as in arm I. Treatment with OxMdG repeats every 14 days for up to 6 courses (12 weeks). Treatment with XELOX repeats every 21 days for up to 4 courses (12 weeks). Patients with disease progression after 12 weeks of therapy are removed from study treatment. Patients with stable or responding disease after 12 weeks of therapy stop treatment and undergo clinical evaluation at least every 6 weeks (treatment break) until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity Quality of life is assessed at baseline, 6 weeks, 12 weeks, and then every 12 weeks thereafter.

After completion of study treatment, patients are followed every 12 weeks for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2,421 patients (807 per treatment arm) will be accrued for this study within 3.5 years.

Keywords
adenocarcinoma of the colon, stage IV colon cancer, adenocarcinoma of the rectum, stage IV rectal cancer
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival at 2 years

Secondary outcomes (5)

  1. Progression-free survival at 2 years

  2. Failure-free survival at 2 years

  3. Response by RECIST criteria at 12 and 24 weeks

  4. Toxicity by NCI Common Toxicity Criteria version 3 throughout treatment and at follow-up

  5. Time of disease control at 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2005 (estimated)
  2. Study startMar 2005
  3. Primary completionMay 2009 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
2,421 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00182715
Sponsor's protocol ID
CDR0000440085
Other IDs
UKM-MRC-COIN-CR10, EU-20516, EUDRACT-2004-002951-16, ISRCTN27286448
Status last verified
Dec 2007
First submitted
15 Sep 2005
Last updated
17 Sep 2013
Results posted
No

Publications

  • Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, Kenny SL, Kay E, Hodgkinson E, Pope M, Rogers P, Wasan H, Falk S, Gollins S, Hickish T, Bessell EM, Propper D, Kennedy MJ, Kaplan R, Maughan TS; MRC COIN Trial Investigators. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011 Jul;12(7):642-53. doi: 10.1016/S1470-2045(11)70102-4. Epub 2011 Jun 5.

    PubMed 21641867

  • Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, Kay E, Mitchell JK, Madi A, Jasani B, James MD, Bridgewater J, Kennedy MJ, Claes B, Lambrechts D, Kaplan R, Cheadle JP; MRC COIN Trial Investigators. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011 Jun 18;377(9783):2103-14. doi: 10.1016/S0140-6736(11)60613-2. Epub 2011 Jun 5.

    PubMed 21641636

  • Adams RA, Meade AM, Madi A, Fisher D, Kay E, Kenny S, Kaplan RS, Maughan TS. Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience. Br J Cancer. 2009 Jan 27;100(2):251-8. doi: 10.1038/sj.bjc.6604877.

    PubMed 19165196

  • Maughan T: Cetuximab (C), oxaliplatin (Ox) and fluoropyrimidine (Fp): toxicity during the first 12 weeks of treatment for the first 804 patients entered into the MRC COIN (CR10) trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-4070, 2007.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cetuximab, capecitabine and fluorouracil in people with Colorectal Cancer, run by Velindre NHS Trust at 82 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 82 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival at 2 years. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00182715, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013; AzTrials last refreshed its copy on 6 Nov 2026.

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