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

NCT ID: NCT00079066

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 572 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-30
• Study Completion Date: 2009-02-10

Brief Summary

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

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.

Conditions

Colorectal Cancer; Quality of Life

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cetuximab

Intervention Type: BIOLOGICAL

quality-of-life assessment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek Jonker, MD

Role: STUDY_CHAIR

Ottawa Regional Cancer Centre

Chris Karapetis, MD

Role: STUDY_CHAIR

National Health and Medical Research Council, Australia

Locations

NHMRC Clinical Trials Centre

Camperdown, New South Wales, Australia

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, Canada

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

Fraser Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Moncton Hospital

Moncton, New Brunswick, Canada

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Newfoundland Cancer Treatment and Research Foundation

St. John's, Newfoundland and Labrador, Canada

Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Belleville General Hospital

Belleville, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Grand River Regional Cancer Centre at Grand River Hospital

Kitchener, Ontario, Canada

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, Canada

Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre

Toronto, Ontario, Canada

St. Michael's Hospital - Toronto

Toronto, Ontario, Canada

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

St. Joseph's Health Centre - Toronto

Toronto, Ontario, Canada

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, Canada

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Hopital Charles Lemoyne

Greenfield Park, Quebec, Canada

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Hopital Du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Countries

Australia; Canada

References

Gupta A, O'Callaghan CJ, Zhu L, Jonker DJ, Wong RPW, Colwell B, Moore MJ, Karapetis CS, Tebbutt NC, Shapiro JD, Tu D, Booth CM. Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial. JCO Oncol Pract. 2023 Jun;19(6):e859-e866. doi: 10.1200/OP.22.00737. Epub 2023 Mar 7.

Reference Type: BACKGROUND

PMID: 36881786 (View on PubMed)

Au HJ, Karapetis CS, O'Callaghan CJ, Tu D, Moore MJ, Zalcberg JR, Kennecke H, Shapiro JD, Koski S, Pavlakis N, Charpentier D, Wyld D, Jefford M, Knight GJ, Magoski NM, Brundage MD, Jonker DJ. Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial. J Clin Oncol. 2009 Apr 10;27(11):1822-8. doi: 10.1200/JCO.2008.19.6048. Epub 2009 Mar 9.

Reference Type: RESULT

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Jonker DJ, Karapetis C, Harbison C, et al.: High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): results from NCIC CTG CO.17-A phase III trial of cetuximab versus best supportive care (BSC).. [Abstract] J Clin Oncol 27 (Suppl 15): A-4016, 2009.

Reference Type: RESULT

Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-126. doi: 10.1093/annonc/mdq309. Epub 2010 Jul 5.

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Reference Type: RESULT

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Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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Reference Type: DERIVED

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Other Identifiers

CAN-NCIC-CO17

Identifier Type: OTHER

Identifier Source: secondary_id

AGITG-CAN-NCIC-CO17

Identifier Type: OTHER

Identifier Source: secondary_id

BMS-CA225-025

Identifier Type: OTHER

Identifier Source: secondary_id

IMCL-CAN-NCIC-CO17

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000353486

Identifier Type: OTHER

Identifier Source: secondary_id

CO17

Identifier Type: -

Identifier Source: org_study_id