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

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ClinicalTrials.gov Identifier: NCT00182715
Recruitment Status : Unknown
Verified December 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : September 16, 2005
Last Update Posted : September 17, 2013
Information provided by:
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: cetuximab Drug: capecitabine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Phase 3

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2421 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : March 2005
Estimated Primary Completion Date : May 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Primary Outcome Measures :
  1. Overall survival at 2 years

Secondary Outcome Measures :
  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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified


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


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


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


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


  • 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


Biologic therapy

  • Not specified


  • 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


  • See Chemotherapy


  • Not specified


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00182715

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Sponsors and Collaborators
Velindre NHS Trust
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Study Chair: Timothy Maughan, MD Velindre NHS Trust
Publications of Results:
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.

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ClinicalTrials.gov Identifier: NCT00182715    
Other Study ID Numbers: CDR0000440085
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: September 17, 2013
Last Verified: December 2007
Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the colon
stage IV colon cancer
adenocarcinoma of the rectum
stage IV rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Protective Agents
Vitamin B Complex