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

NCT00079066 | Completed Phase 3 DMC

• 6 other identifiers: CO17CAN-NCIC-CO17AGITG-CAN-NCIC-CO17BMS-CA225-025IMCL-CAN-NCIC-CO17CDR0000353486
• Study Type: interventional
• Target: 572
• Locations: 2 countries
• Sites: 33

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.

Conditions

Colorectal Cancer; Quality of Life

Keywords

quality of life; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

Secondary Outcomes (6)

• 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

Interventions

cetuximab BIOLOGICAL

quality-of-life assessment PROCEDURE

Eligibility Criteria

• Age: 16 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Australasian Gastro-Intestinal Trials Group: collaborator

Study Sites (33)

NHMRC Clinical Trials Centre

Camperdown, New South Wales, 1450, Australia

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Fraser Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, V3V 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Moncton Hospital

Moncton, New Brunswick, E1C 6ZB, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Newfoundland Cancer Treatment and Research Foundation

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Belleville General Hospital

Belleville, Ontario, K8N 5K5, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

Grand River Regional Cancer Centre at Grand River Hospital

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

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

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, L2R 5K3, Canada

Location

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

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

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

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital - Toronto

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital - Toronto

Toronto, Ontario, M5G 1X5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

St. Joseph's Health Centre - Toronto

Toronto, Ontario, M6R 1B5, Canada

Location

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, N8W 2X3, Canada

Location

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Hopital Charles Lemoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2L 4MI, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Hopital Du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (13)

• 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.

  PMID: 36881786 BACKGROUND

• 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.

  PMID: 19273701 RESULT

• 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.

  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.

  PMID: 20603436 RESULT

• Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. doi: 10.1056/NEJMoa0804385.

  PMID: 18946061 RESULT

• 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.

  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.

  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.

  RESULT

• Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. doi: 10.1056/NEJMoa071834.

  PMID: 18003960 RESULT

• Nicholls DL, Xu MC, Zhan L, Sharma D, Hueniken K, Chiasson K, Wahba M, Brown MC, Grant B, Shapiro J, Karapetis CS, Simes J, Jonker D, Tu D, O'Callaghan C, Chen E, Liu G. Machine Learning Models of Early Longitudinal Toxicity Trajectories Predict Cetuximab Concentration and Metastatic Colorectal Cancer Survival in the Canadian Cancer Trials Group/AGITG CO.17/20 Trials. JCO Clin Cancer Inform. 2025 Apr;9:e2400114. doi: 10.1200/CCI.24.00114. Epub 2025 Apr 11.

  PMID: 40215447 DERIVED

• 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. The association of health-care contact days with physical function and survival in CCTG/AGITG CO.17. J Natl Cancer Inst. 2024 Aug 1;116(8):1313-1318. doi: 10.1093/jnci/djae077.

  PMID: 38656931 DERIVED

• Loree JM, Dowers A, Tu D, Jonker DJ, Edelstein DL, Quinn H, Holtrup F, Price T, Zalcberg JR, Moore MJ, Karapetis CS, O'Callaghan CJ, Waring P, Kennecke HF, Hamilton SR, Kopetz S. Expanded Low Allele Frequency RAS and BRAF V600E Testing in Metastatic Colorectal Cancer as Predictive Biomarkers for Cetuximab in the Randomized CO.17 Trial. Clin Cancer Res. 2021 Jan 1;27(1):52-59. doi: 10.1158/1078-0432.CCR-20-2710. Epub 2020 Oct 21.

  PMID: 33087330 DERIVED

• Hay AE, Pater JL, Corn E, Han L, Camacho X, O'Callaghan C, Chong N, Bell EN, Tu D, Earle CC. Pilot study of the ability to probabilistically link clinical trial patients to administrative data and determine long-term outcomes. Clin Trials. 2019 Feb;16(1):14-17. doi: 10.1177/1740774518815653. Epub 2018 Nov 22.

  PMID: 30466310 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Derek Jonker, MD

  Ottawa Regional Cancer Centre

  STUDY CHAIR

• Chris Karapetis, MD

  National Health and Medical Research Council, Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 9, 2004
• Study Start: December 30, 2003
• Primary Completion: November 3, 2006
• Study Completion: February 10, 2009
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CA (32)