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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2007 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00182715
First received: September 15, 2005
Last updated: September 16, 2013
Last verified: December 2007
  Purpose

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 Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival at 2 years [ Designated as safety issue: No ]
  • Failure-free survival at 2 years [ Designated as safety issue: No ]
  • Response by RECIST criteria at 12 and 24 weeks [ Designated as safety issue: No ]
  • Toxicity by NCI Common Toxicity Criteria version 3 throughout treatment and at follow-up [ Designated as safety issue: Yes ]
  • Time of disease control at 2 years [ Designated as safety issue: No ]

Estimated Enrollment: 2421
Study Start Date: March 2005
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182715

  Show 82 Study Locations
Sponsors and Collaborators
Velindre NHS Trust
Investigators
Study Chair: Timothy Maughan, MD Velindre NHS Trust
  More Information

Additional Information:
Publications:
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.

ClinicalTrials.gov Identifier: NCT00182715     History of Changes
Other Study ID Numbers: CDR0000440085, UKM-MRC-COIN-CR10, EU-20516, EUDRACT-2004-002951-16, ISRCTN27286448
Study First Received: September 15, 2005
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

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:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Cetuximab
Oxaliplatin
Levoleucovorin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antidotes
Protective Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 30, 2014