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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 16 and over Other, Pharmaceutical / Industry CAN-NCIC-CO17 AGITG-CAN-NCIC-CO17, BMS-CA225-025, IMCL-CAN-NCIC-CO17, NCT00079066, CO17

Objectives

Primary

1. 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

1. Compare the time to disease progression in patients treated with these regimens.
2. Compare the objective response rate in patients treated with these regimens.
3. Compare the quality of life of patients treated with these regimens.
4. Compare the health utilities of patients treated with these regimens.
5. Conduct a comparative economic evaluation in patients treated with these regimens.
6. Determine the safety profile of cetuximab in these patients.

Entry Criteria

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]

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

Patient Characteristics:

Age

• 16 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• 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

Expected Enrollment

A total of 500 patients (250 per treatment arm) will be accrued for this study within 20 months.

Outcomes

Overall survival

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

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.

Mittmann N, Au HJ, Tu D, et al.: A prospective economic analysis of cost-effectiveness of cetuximab for metastatic colorectal cancer patients from the NCIC CTG and AGITG CO.17 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-6528, 2008.

O'Callaghan CJ, Tu D, Karapetis CS, et al.: The relationship between the development of rash and clinical and quality of life outcomes in colorectal cancer patients treated with cetuximab in NCIC CTG CO.17. [Abstract] J Clin Oncol 26 (Suppl 15): A-4130, 2008.

Au H, Karapetis C, Jonker D, et al.: Quality of life in patients with advanced colorectal cancer treated with cetuximab: results of the NCIC CTG and AGITG CO.17 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-4002, 2007.

Jonker DJ, Karapetis CS, Moore M, et al.: Randomized phase III trial of cetuximab monotherapy plus best supportive care (BSC) versus BSC alone in patients with pretreated metastatic epidermal growth factor receptor (EGFR)-positive colorectal carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the Australasian Gastro-Intestinal Trials Group (AGITG). [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. 2007.

Jonker DJ, O'Callaghan CJ, Karapetis CS, et al.: Cetuximab for the treatment of colorectal cancer. N Engl J Med 357 (20): 2040-8, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Derek Jonker, MD, Protocol chair		Ph: 613-737-7700 ext. 70168; 888-627-5346

Australasian Gastro-Intestinal Trials Group

Chris Karapetis, MD, Protocol chair		Ph: 61-8-8204-8997

Registry Information
Official Title		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
Trial Start Date		2003-08-28
Registered in ClinicalTrials.gov		NCT00079066
Date Submitted to PDQ		2004-01-20
Information Last Verified		2005-08-08

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