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

Phase 3

• Conditions: Colorectal Cancer

• Registration Number: NCT00182715
• Lead Sponsor: Velindre NHS Trust

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.

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.

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2005-09-15
• Study First Submitted QC: 2005-09-15
• Study First Posted: 2005-09-16
• Status Verified: 2007-12
• Primary Completion: 2009-05
• Last Update Submitted: 2013-09-16
• Last Update Posted: 2013-09-17

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2421

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall survival at 2 years

Secondary Outcome Measures

Name	Time	Method
Progression-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
Failure-free survival at 2 years

Trial Locations

Locations (81)

Mercy University Hospital; 🇮🇪 Cork, Ireland

Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital; 🇮🇪 Dublin, Ireland

St. Vincent's University Hospital; 🇮🇪 Dublin, Ireland

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

Mater Private Hospital; 🇮🇪 Dublin, Ireland

St. James's Hospital; 🇮🇪 Dublin, Ireland

Beaumont Hospital; 🇮🇪 Dublin, Ireland

Galway University Hospital; 🇮🇪 Galway, Ireland

Mid-Western Cancer Centre at Mid-Western Regional Hospital; 🇮🇪 Limerick, Ireland

Waterford Regional Hospital; 🇮🇪 Waterford, Ireland

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