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

NCT00182715 | Unknown Phase 3

• 5 other identifiers: CDR0000440085UKM-MRC-COIN-CR10EU-20516EUDRACT-2004-002951-16ISRCTN27286448
• Study Type: interventional
• Target: 2,421
• Locations: 2 countries
• Sites: 82

Brief 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. 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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; stage IV colon cancer; adenocarcinoma of the rectum; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival at 2 years

Secondary Outcomes (5)

• Progression-free survival at 2 years

• Failure-free survival at 2 years

• Response by RECIST criteria at 12 and 24 weeks

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

• Time of disease control at 2 years

Interventions

cetuximab BIOLOGICAL

capecitabine DRUG

fluorouracil DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Velindre NHS Trust: lead

Study Sites (82)

Mercy University Hospital

Cork, Ireland

Location

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

Dublin, 24, Ireland

Location

St. Vincent's University Hospital

Dublin, 4, Ireland

Location

Mater Misericordiae University Hospital

Dublin, 7, Ireland

Location

Mater Private Hospital

Dublin, 7, Ireland

Location

St. James's Hospital

Dublin, 8, Ireland

Location

Beaumont Hospital

Dublin, 9, Ireland

Location

Galway University Hospital

Galway, Ireland

Location

Mid-Western Cancer Centre at Mid-Western Regional Hospital

Limerick, 0009, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

North Hampshire Hospital

Basingstoke, England, RG24 9NA, United Kingdom

Location

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B12 2TH, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, England, FY3 8NR, United Kingdom

Location

Royal Bournemouth Hospital NHS Trust

Bournemouth, England, BH7 7DW, United Kingdom

Location

Bradford Royal Infirmary

Bradford, England, BD9 6RJ, United Kingdom

Location

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Queen's Hospital

Burton-on-Trent, England, DE13 0RB, United Kingdom

Location

West Suffolk Hospital

Bury St Edmunds, England, IP33 2QZ, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 0QQ, United Kingdom

Location

Cumberland Infirmary

Carlisle, England, CA2 7HY, United Kingdom

Location

Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Essex County Hospital

Colchester, England, C03 3NB, United Kingdom

Location

Derbyshire Royal Infirmary

Derby, England, DE1 2QY, United Kingdom

Location

Dorset County Hospital

Dorchester, England, DT1 2JY, United Kingdom

Location

Eastbourne District General Hospital

Eastbourne, England, BN21 2UD, United Kingdom

Location

Princess Alexandra Hospital

Essex, England, CM20 1QX, United Kingdom

Location

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

Guildford, England, GU2 7XX, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, HD3 3EA, United Kingdom

Location

Princess Royal Hospital at Hull and East Yorkshire NHS Trust

Hull, England, HU8 9HE, United Kingdom

Location

Hinchingbrooke Hospital

Huntingdon, England, PE18 6NT, United Kingdom

Location

Cookridge Hospital

Leeds, England, LS16 6QB, United Kingdom

Location

Aintree University Hospital

Liverpool, England, L9 7AL, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

Helen Rollason Cancer Care Centre at North Middlesex Hospital

London, England, N18 1QX, United Kingdom

Location

University College of London Hospitals

London, England, NW1 2PG, United Kingdom

Location

Royal Free and University College Medical School

London, England, NW3 2PF, United Kingdom

Location

Queen Elizabeth Hospital - Woolwich

London, England, SE18 4QH, United Kingdom

Location

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

London, England, SE5 9NU, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

Royal Marsden - London

London, England, SW3 6JJ, United Kingdom

Location

Hammersmith Hospital

London, England, W12 OHS, United Kingdom

Location

St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

Charing Cross Hospital

London, England, W6 8RF, United Kingdom

Location

Southport and Formby District General Hospital

Merseyside, England, CH63 4JY, United Kingdom

Location

St. Mary's Hospital

Newport, England, PO30 5TG, United Kingdom

Location

North Tyneside Hospital

North Shields, England, NE29 8NH, United Kingdom

Location

Northampton General Hospital NHS Trust

Northampton, England, NN6 8BJ, United Kingdom

Location

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, HA6 2RN, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, England, NG5 1PB, United Kingdom

Location

Peterborough Hospitals Trust

Peterborough, England, PE3 6DA, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Poole Hospital NHS Trust

Poole Dorset, England, BH15 2JB, United Kingdom

Location

Portsmouth Oncology Centre at Saint Mary's Hospital

Portsmouth Hants, England, PO3 6AD, United Kingdom

Location

Whiston Hospital

Prescot Merseyside, England, L35 5DR, United Kingdom

Location

Royal Preston Hospital

Preston, England, PR2 9HT, United Kingdom

Location

Conquest Hospital

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

Location

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

Location

Scarborough General Hospital

Scarborough, England, YO12 6QL, United Kingdom

Location

South Tyneside District Hospital

South Shields, England, NE34 0PL, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

University Hospital of North Staffordshire

Stoke-on-Trent, England, ST4 7LN, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, England, SR4 7TP, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Great Western Hospital

Swindon, England, SN3 6BB, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

Location

Walsall Manor Hospital

Walsall, England, WS2 9PS, United Kingdom

Location

Good Hope Hospital Trust

West Midlands, England, B75 7RR, United Kingdom

Location

Royal Hampshire County Hospital

Winchester, England, SO22 5DG, United Kingdom

Location

Worcester Royal Hospital

Worcester, England, WR5 1DD, United Kingdom

Location

Worthing Hospital

Worthing, England, BN11 2DH, United Kingdom

Location

Yeovil District Hospital

Yeovil, England, BA21 4AT, United Kingdom

Location

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, BT8 8JR, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Hairmyres Hospital

East Kilbride, Scotland, G75 8RG, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

Location

South West Wales Cancer Institute

Swansea, Wales, SA2 8QA, United Kingdom

Location

Wrexham Maelor Hospital

Wrexham, Wales, LL13 7TD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 21641867 RESULT

• 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.

  PMID: 21641636 RESULT

• 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.

  PMID: 19165196 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Timothy Maughan, MD

  Velindre NHS Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 16, 2005
• Study Start: March 1, 2005
• Primary Completion: May 1, 2009
• Last Updated: September 17, 2013

Record last verified: 2007-12

Locations

IE (10); GB (72)