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Clinical Trials (PDQ®)

  • First Published: 9/9/2005
  • Last Modified: 5/8/2013

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Phase III Randomized Study of Continuous Combination Chemotherapy Comprising Oxaliplatin, Leucovorin Calcium, and Fluorouracil (OxMdG) or Oxaliplatin and Capecitabine (XELOX) With Versus Without Cetuximab Versus Intermittent Combination Chemotherapy With OxMdG or XELOX as First-Line Therapy in Patients with Metastatic Colorectal Adenocarcinoma. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Cetuximab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosed18 and overOtherUKM-MRC-COIN-CR10
EU-20516, NCT00182715, EUDRACT-2004-002951-16, ISRCTN27286448, COIN

Objectives

Primary

  1. 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

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

Entry Criteria

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

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)

Patient Characteristics:

Age

  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3

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

Expected Enrollment

2421

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

Outcomes

Primary Outcome(s)

Overall survival at 2 years

Secondary Outcome(s)

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

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

Published Results

Adams RA, Meade AM, Seymour MT, et al.: 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 12 (7): 642-53, 2011.[PUBMED Abstract]

Maughan TS, Adams RA, Smith CG, et al.: 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 377 (9783): 2103-14, 2011.[PUBMED Abstract]

Adams RA, Meade AM, Madi A, et al.: Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience. Br J Cancer 100 (2): 251-8, 2009.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

Velindre Cancer Center at Velindre Hospital

Timothy Maughan, MD, Protocol chair
Ph: 44-2920-316-904

Registry Information
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)
Trial Start Date 2005-03-08
Trial Completion Date 2009-05-01 (estimated)
Registered in ClinicalTrials.gov NCT00182715
Date Submitted to PDQ 2005-07-06
Information Last Verified 2007-12-11

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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