Cetuximab + Best Supportive Care Compared With Best Supportive Care Alone in Metastatic Epidermal Growth Factor Receptor-Positive Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can target tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Best supportive care is the use of drugs and other treatments to improve the quality of life of patients. Combining cetuximab with best supportive care may slow the growth of the tumor and help patients live longer and more comfortably. It is not yet known whether cetuximab combined with best supportive care is more effective than best supportive care alone in treating metastatic epidermal growth factor receptor-positive colorectal cancer. PURPOSE: This randomized phase III trial is studying cetuximab and best supportive care to see how well they work compared to best supportive care alone in treating patients with metastatic epidermal growth factor receptor-positive colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Compare survival of patients with metastatic epidermal growth factor receptor-positive colorectal cancer treated with cetuximab and best supportive care vs best supportive care alone. Secondary Compare the time to disease progression in patients treated with these regimens. Compare the objective response rate in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. Compare the health utilities of patients treated with these regimens. Conduct a comparative economic evaluation in patients treated with these regimens. Determine the safety profile of cetuximab in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center and ECOG performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive an initial loading dose of cetuximab IV over 120 minutes on day 1. Patients continue to receive maintenance infusions of cetuximab IV over 60 minutes weekly. Patients also receive best supportive care, defined as measures designed to provide palliation of symptoms and improve quality of life as much as possible. Arm II: Patients receive best supportive care as in arm I. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, and then at 4, 8, 16, and 24 weeks (or until deterioration to ECOG PS 4 or hospitalization for end-of-life care). Patients are followed every 4 weeks. PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this study within 20 months.

Official Title
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A Phase III Randomized Study of Cetuximab (Erbitux™, C225) and Best Supportive Care Versus Best Supportive Care in Patients With Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma

Conditions
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Colorectal Cancer, Quality of Life

Intervention / Treatment
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* Biological: cetuximab
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer Metastatic disease Epidermal growth factor receptor (EGFR)-positive by immunochemistry Measurable or evaluable disease Not amenable to standard curative therapy Best supportive care is the only available option Must have received a prior thymidylate synthase inhibitor (e.g., fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) in the adjuvant or metastatic setting Combination therapy with oxaliplatin or irinotecan allowed Must have failed* a prior regimen containing irinotecan and a prior regimen containing oxaliplatin for metastatic disease OR relapsed within 6 months after an adjuvant regimen containing irinotecan or oxaliplatin OR have documented unsuitability for such regimens No symptomatic CNS metastases NOTE: *Failure is defined as either disease progression (clinical or radiological) or intolerance to the regimen PATIENT CHARACTERISTICS: Age 16 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8.0 g/dL Hepatic AST and ALT ≤ 5 times upper limit of normal (ULN) Bilirubin ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Cardiovascular No uncontrolled angina No arrhythmias No cardiomyopathy No congestive heart failure No myocardial infarction* within the past 6 months NOTE: *Pre-treatment ECG as only evidence of infarction is allowed Pulmonary No severe restrictive lung disease No interstitial lung disease by chest x-ray Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment No active pathological condition that would preclude study participation No psychological or geographical condition that would preclude study compliance No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No prior cetuximab No prior murine monoclonal antibody therapy (e.g., edrecolomab) Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy and recovered No concurrent chemotherapy Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Concurrent palliative radiotherapy allowed except to index lesions Surgery At least 4 weeks since prior major surgery and recovered Other No prior EGFR-targeted therapy (e.g., erlotinib or gefitinib) More than 30 days since prior experimental therapeutic agents More than 4 weeks since prior investigational agents No concurrent enrollment in another clinical study No other concurrent EGFR-targeted therapy No other concurrent non-cytotoxic experimental agents

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Procedure: quality-of-life assessment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 
| Objective response rate |  |  | 
| Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire -C30 (EORTC QLQ-C30) |  |  | 
| Health utilities by Health Utilities Index 13 (HU 13) |  |  | 
| Economic evaluation |  |  | 
| Safety profile |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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quality of life, stage IV colon cancer, recurrent colon cancer, recurrent rectal cancer, stage IV rectal cancer