Overview

This trial is active, not recruiting.

Condition colorectal cancer
Treatments cetuximab, capecitabine, fluorouracil, leucovorin calcium, oxaliplatin
Phase phase 3
Target EGFR
Sponsor Velindre NHS Trust
Start date March 2005
End date May 2009
Trial size 2421 participants
Trial identifier NCT00182715, CDR0000440085, EU-20516, EUDRACT-2004-002951-16, ISRCTN27286448, UKM-MRC-COIN-CR10

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Overall survival at 2 years
time frame:

Secondary Outcomes

Measure
Progression-free survival at 2 years
time frame:
Failure-free survival at 2 years
time frame:
Response by RECIST criteria at 12 and 24 weeks
time frame:
Toxicity by NCI Common Toxicity Criteria version 3 throughout treatment and at follow-up
time frame:
Time of disease control at 2 years
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

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)

Additional 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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).