NCIC CO.17

A phase III randomised study of cetuximab (ERBITUXTM, C225) and best supportive care versus best supportive care in patients with pre-treated metastatic epidermal growth factor receptor (EGFR) positive colorectal carcinoma.

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Trial Status

Completed

Cancer Type

Colorectal Cancer

Aim

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.

Summary

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.

Trial Status

Completed

Cancer Type

Colorectal Cancer

Publication Reference

  1. Liu G, Tu D, Lewis M, Cheng D, Sullivan LA, Chen Z, Morgen E, Simes J, Price TJ, Tebbutt NC, Shapiro JD, Jeffery GM, Mellor JD, Mikeska T, Virk S, Shepherd LE, Jonker DJ, O’Callaghan CJ, Zalcberg JR, Karapetis CS, Dobrovic A. Fc-gamma receptor polymorphisms, cetuximab therapy, and survival in the NCIC CTG CO.17 trial of colorectal cancer. Clinical Cancer Research 2016; 22(10): 2435–2444.
  2. Brule SY, Jonker DJ, Karapetis CS, O’Callaghan CJ, Moore MJ, Wong R, Tebbutt NC, Underhill C, Yip D, Zalcberg JR, Tu D, Goodwin RA. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. European Journal of Cancer 2015; 51(11): 1405-1414.
  3. Jonker D, Karapetis C, Harbison C, O’Callaghan C, Tu D, Simes R, Malone D, Langer C, Tebbutt N, Price T, Shapiro J, Siu L, Wong R, Bjarnason G, Moore M, Zalcberg J, Khambata-Ford S. Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer. British Journal of Cancer 2014; 110(3): 648–55.
  4. Karapetis CS, Jonker D, Daneshmand M, Hanson JE, O’Callaghan CJ, Marginean C, Zalcberg JR, Simes J, Moore MJ, Tebbutt NC, Price TJ, Shapiro JD, Pavlakis N, Gibbs P, Van Hazel GA, Lee U, Haq R, Virk S, Tu D, Lorimer IA. PIK3CA, BRAF and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer—results from NCIC CTG/AGITG CO.17. Clinical Cancer Research 2014; 20(3): 744–753.
  5. Sommeijer DW, Karapetis CS, Zalcberg JR, Tu D, Jonker DJ, Simes J, Tebbutt N, Yip D, Price TJ, O’Callaghan CJ. The relationship between rash, tumour KRAS mutation status and clinical and quality of life outcomes in patients with advanced colorectal cancer treated with cetuximab in the NCIC CTG/AGITG CO.17. Acta Oncologica 2014; 53(7): 877–884.
  6. Harbison CT, Horak CE, Ledeine JM, Mukhopadhyay P, Malone DP, O’Callaghan C, Jonker DJ, Karapetis CS, Khambata-Ford S, Gustafson N, Trifan OC, Chang SC, Ravetto P, Green GA 4th. Validation of companion diagnostic for detection of mutations in codons 12 and 13 of the KRAS gene in patients with metastatic colorectal cancer: analysis of the NCIC CTG CO.17 trial. Archives of Pathology & Laboratory Medicine 2013; 137(6): 820–827.2
  7. Vickers MM, Karapetis CS, Tu D, O’Callaghan CJ, Price TJ, Tebbutt NC, Van Hazel G, Shapiro JD, Pavlakis N, Gibbs P, Blondal J, Lee U, Meharchand JM, Burkes RL, Rubin SH, Simes J, Zalcberg JR, Moore MJ, Zhu L, Jonker DJ. Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17. Annals of Oncology 2013; 24(4): 953–960.
  8. 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. Annals of Oncology 2011; 22(1): 118–126.
  9. De Roock S, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O’Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, Bardelli A, Tejpar S. Association of Kras p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 2010; 304(16): 1812–1820.
  10. Au HJ, Karapetis CS, O’Callaghan CJ, Tu D, Moore MJ, Zalcberg J, 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 advanced colorectal cancer patients treated with cetuximab: overall and Kras-specific results of the NCIC CTG and AGITG CO.17 trial. Journal of Clinical Oncology 2009; 27(11): 1822–1828.
  11. Mittmann N, Au HJ, Tu D, O’Callaghan CJ, Isogai PK, Karapetis CS, Zalcberg JR, Evans WK, Moore MJ, Siddiqui J, Findlay B, Colwell B, Simes J, Gibbs P, Links M, Tebbutt NC, Jonker DJ; Working Group on Economic Analysis of the National Cancer Institute of Canada Clinical Trials Group–Australasian Gastrointestinal Interest Group. Prospective cost-effectiveness analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial. Journal of the National Cancer Institute 2009: 101(17): 1182–1192.
  12. 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. New England Journal of Medicine 2008; 359(17): 1757–1765.
  13. 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. New England Journal of Medicine 2007; 357(20): 2040–2048.

Conference Presentation Reference

  1. Sud S, O’Callaghan CJ, Jonker C, Karapetis CS, Price TJ, Tebbutt NC, Shapiro JD, Van Hazel GA, Pavlakis N, Gibbs P, Jeffery M, Siu LL, Gill S, Wong R, Jonker DJ, Tu D, Goodwin RA. Hypertension as a predictor of outcome and treatment response to cetuximab: a retrospective analysis of NCIC CTG CO.17. Gastrointestinal Cancers Symposium; 21–23 Jan 2016; San Francisco.
  2. Sud S, O’Callaghan CJ, Karapetis CS, Jonker C, Price TJ, Tebbutt NC, Shapiro J, Van Hazel GA, Pavlakis N, Gibbs P, Jeffery M, Siu LL, Gill S, Wong R, Jonker DJ, Tu D, Goodwin RA. Hypertension and beta-blocker use as prognostic and predictive factors in metastatic colorectal cancer: aretrospective analysis of NCIC CTG CO.17. American Society of Clinical Oncology Annual Meeting; 3–7 Jun 2016; Chicago.
  3. Brulé S, Jonker D, Karapetis C, O’Callaghan C, Moore M, Wong R, Tebbutt N, Underhill C, Yip D, Zalcberg J, Tu D, Goodwin R. Location of colon cancer (right-sided versus left-sided) as a predictor of benefit from cetuximab in NCIC CTG CO.17. American Society of Clinical Oncology Annual Meeting; 31 May–4 Jun 2013; Chicago. Journal of Clinical Oncology; 31(suppl.): 3528.
  4. Jonker D, Karapetis C, O’Callaghan C, Marginean C, Zalcberg J, Simes J, Moore M, Tebbutt N, Price T, Daneshmand M, Hanson J, Shapiro J, Pavlakis M, Gibbs P, Van Hazel G, Lee U, Haq R, Virk S, Tu D, Lorimer I, NCIC Clinical Trials Group and the Australasian Gastro-Intestinal Trials Group. BRAF, PIK3CA, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer: results from NCIC CTG/AGITG CO.17. American Society of Clinical Oncology; 1–5 May Chicago. Abstract 3515.
  5. Elimova E, O Callaghan CJ, Tu D, Karapetis CS, Price TJ, Zhu L, Zalcberg JR, Simes J, Jonker DJ. Cetuximab related hypersensitivity reactions: An analysis of timing, demographics, and outcomes from the AGITG / NCIC CTG CO.17 trial. American Society of Clinical Oncology Annual Meeting; 4–8 Jun 2011; Chicago.
  6. O’Callaghan CJ, Tu D, Karapetis CS, Au HJ, Moore MJ, Tebbutt NC, Trudeau MG, Price TJ, Yip D, Jonker DJ. The relationship between the development of rash and clinical and health-related quality of life outcomes by KRAS mutation status in colorectal cancer patients treated with cetuximab in NCIC CTG CO.17. American Society of Clinical Oncology Annual Meeting; 4–8 Jun 2011; Chicago.
  7. Van Hazel GA, Tu D, Tebbutt C, Jonker DJ, Price TJ, O’Callaghan C, Zalcberg JR, Simes J, Yip D, Jefford M, Strickland AH, Burnell MJ, Karapetis CS. Early change in tumor size from waterfall plot analysis and RESIST response as predictor of overall survival in advanced, chemotherapy-refractory colorectal cancer: NCIC CTG/AGITG CO.17 study. American Society of Clinical Oncology Annual Meeting; 4–8 Jun 2011; Chicago.
  8. Vickers MM, Karapetis C, Tu D, Zalcberg J, O’Callaghan C, Simes J, Moore M, Zhu L, Jonker DJ. The influence of hypomagnesemia on overall survival in a phase III randomized study of cetuximab plus best supportive care (BSC) versus BSC: NCIC CTG / AGITG CO.17. American Society of Clinical Oncology Annual Meeting; 4–8 Jun 2011; Chicago.
  9. Jonker D, Karapetis C, Harbison C, O’Callaghan C, Tu D, Simes J, Xu LA, Moore M, Zalcberg J, Khambata-ford S. High epiregulin gene expression plus KRAS wild-type status predict for cetuximab benefit in the treatment of advanced colorectal cancer: results from NCIC CTG CO.17: a phase III trial of cetuximab vs best supportive care. Annual Meeting of the American Society of Clinical Oncology; 29 May–2 Jun 2009; Orlando.
  10. Powell ED, Asmis T, Jonker D, Tu C, Karapetis C, Jeffery M, O’Callaghan C. Comorbidity and overall survival in cetuximab-treated patients with advanced colorectal cancer—results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Annual Meeting of the American Society of Clinical Oncology; 29 May–2 Jun 2009; Orlando. Journal of Clinical Oncology 2009; 27: 15s. Abstract 4074.
  11. Karapetis C, Khambata-Ford S, Jonker D, O’Callaghan C, Tu D, Vachan B, Simes J, Langer C, Moore M, Zalcberg J. K-ras mutation status is a predictive biomarker for cetuximab benefit in the treatment of advanced colorectal cancer — results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. 33rd Congress of the European Society of Medical Oncology; 12–16 Sep 2008; Stockholm. Annals of Oncology 2008; 19: viii2. Abstract LBA6.
  12. Mittmann N, Au HJ, Tu D, O’Callaghan CJ, Karapetis CS, Moore MJ, Zalcberg J, Simes J, Evans WK, Jonker DJ. A prospective economic analysis of cost-effectiveness of cetuximab for metastatic colorectal cancer patients from the NCIC CTG and AGITG CO.17 trial. 44th Annual Meeting of the American Society of Clinical Oncology; 30 May–3 Jun 2008; Chicago. Journal of Clinical Oncology 2008; 26 (May 20). Abstract 6528.
  13. O’Callaghan CJ, Tu D, Karapetis CS, Au HJ, Moore MJ, Zalcberg JR, Trudeau M, Yip D, Vachan B, Jonker DJ. The relationship between the development of rash and clinical and quality of life outcomes in colorectal cancer patients treated with cetuximab in NCIC–CTC CO.17. 44th Annual Meeting of the American Society of Clinical Oncology; 30 May–3 Jun 2008; Chicago. Journal of Clinical Oncology 2008; 26 (May 20). Abstract 4130.
  14. Au H, Karapetis C, Jonker D, O’Callaghan C, Kennecke H, Shapiro J, Tu D, Wierzbicki R, Zalcberg J, Moore M. Quality of life in patients with advanced colorectal cancer treated with cetuximab: results of the NCIC CTG and AGITG CO.17 trial. 43rd Annual Meeting of the American Society of Clinical Oncology; 1–5 Jun 2007; Chicago. Journal of Clinical Oncology 2007; 25 (18S, Part 1): 4002.
  15. Jonker DJ, Karapetis CS Moore MJ, Zalcberg JR, Tu D, Au H, Berry S, Krahn M, Simes RJ, Tebbutt N, van Hazel G, O’Callaghan CJ. A phase III randomized study of cetuximab (Erbitux, C225) and best supportive care versus best supportive care in patients with pretreated metastatic colorectal carcinoma. American Association for Cancer Research Annual Meeting; 14–18 Apr 2007; Los Angeles.
  16. Diakos CI, Tu D, Gebski V, Yip S, Wilson K, Karapetis C, O’Callaghan CJ, Shapiro J, Tebbutt N, Jonker DJ, Sui LL, Wong R, Doyle C, Strickland AH, Price TJ, Simes J, Clarke S. Is the derived neutrophil to lymphocyte ratio an independent prognostic marker in patients with metastatic colorectal cancer? Analysis of the CO.17 and CO.20 studies. European Society for Medical Oncology 41st Congress; 7–11 Oct 2016 2016; Copenhagen.

Aim

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.

Summary

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.

Principal Investigator

Dr Chris Karapetis, Medical Oncologist Flinders Medical Centre, SA

Funding

Bristol Myers Squibb Company (USA)
National Cancer Institute of Canada Clinical Trials Group