Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer

Summary

This randomized phase III trial was originally designed to compare three different combination chemotherapy regimens to see how well they work. As of September 1, 2004, the study was expanded to a total of 6 arms (the original 3 arms (A, B, C) and 3 additional arms which were the same as the first 3 but with cetuximab) in treating patients who have undergone surgery for stage III colon cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with monoclonal antibody therapy and giving them after surgery may kill any remaining tumor cells. It was not known at the time this study was developed which combination chemotherapy regimen is more effective after surgery in treating colon cancer. This study had several key changes, based on the results of other phase III trials. As of 6/1/2005, patients no longer received irinotecan on this study and treatment arms B, C, E, and F were discontinued. Patients on arms B and C crossed to arm A. Patients on arms E and F crossed to arm D. Patients on arms C and F who had not gotten to irinotecan continued on arms A and D, respectively. As of 8/18/2008, pre-screening for Kirsten rat sarcoma (KRAS) status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. Patients on arm G were treated per physician discretion and followed for disease and survival status. KRAS was determined in a central laboratory and was process for all patients on this study. The primary endpoint of this study was modified on 8/18/2008 to focus on patients having wild-type KRAS tumors. All modifications were approved by the Central Institution Review Board, local Institutional Review Boards, NCI, and the NCCTG Data Safety Monitoring Board.

Timeline

Start

2004-02

Primary completion

2012-11

Completion

2012-11

Publications

• Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.
• Saberzadeh-Ardestani B, Foster NR, Lee HE, Shi Q, Alberts SR, Smyrk TC, Sinicrope FA. Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance]. Ann Oncol. 2022 Nov;33(11):1159-1167. doi: 10.1016/j.annonc.2022.07.1942. Epub 2022 Aug 10.
• Azizi Z, Zheng C, Mosquera L, Pilote L, El Emam K; GOING-FWD Collaborators. Can synthetic data be a proxy for real clinical trial data? A validation study. BMJ Open. 2021 Apr 16;11(4):e043497. doi: 10.1136/bmjopen-2020-043497.
• Cohen R, Taieb J, Fiskum J, Yothers G, Goldberg R, Yoshino T, Alberts S, Allegra C, de Gramont A, Seitz JF, O'Connell M, Haller D, Wolmark N, Erlichman C, Zaniboni A, Lonardi S, Kerr R, Grothey A, Sinicrope FA, Andre T, Shi Q. Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials. J Clin Oncol. 2021 Feb 20;39(6):642-651. doi: 10.1200/JCO.20.01600. Epub 2020 Dec 23.
• Labadie JD, Hua X, Harrison TA, Banbury BL, Huyghe JR, Sun W, Shi Q, Yothers G, Alberts SR, Sinicrope FA, Goldberg RM, George TJ, Penney KL, Phipps AI, Cohen SA, Peters U, Chan AT, Newcomb PA. Genetic Predictors of Severe Skin Toxicity in Patients with Stage III Colon Cancer Treated with Cetuximab: NCCTG N0147 (Alliance). Cancer Epidemiol Biomarkers Prev. 2021 Feb;30(2):404-411. doi: 10.1158/1055-9965.EPI-20-1274. Epub 2020 Nov 17.
• Lee H, Sha D, Foster NR, Shi Q, Alberts SR, Smyrk TC, Sinicrope FA. Analysis of tumor microenvironmental features to refine prognosis by T, N risk group in patients with stage III colon cancer (NCCTG N0147) (Alliance). Ann Oncol. 2020 Apr;31(4):487-494. doi: 10.1016/j.annonc.2020.01.011. Epub 2020 Jan 25.
• Penney KL, Banbury BL, Bien S, Harrison TA, Hua X, Phipps AI, Sun W, Song M, Joshi AD, Alberts SR, Allegra CJ, Atkins J, Colangelo LH, George TJ, Goldberg RM, Lucas PC, Nair SG, Shi Q, Sinicrope FA, Wolmark N, Yothers G, Peters U, Newcomb PA, Chan AT. Genetic Variant Associated With Survival of Patients With Stage II-III Colon Cancer. Clin Gastroenterol Hepatol. 2020 Nov;18(12):2717-2723.e3. doi: 10.1016/j.cgh.2019.11.046. Epub 2019 Dec 4.
• Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, Andre T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol. 2019 Sep 1;30(9):1466-1471. doi: 10.1093/annonc/mdz208.
• Zaanan A, Shi Q, Taieb J, Alberts SR, Meyers JP, Smyrk TC, Julie C, Zawadi A, Tabernero J, Mini E, Goldberg RM, Folprecht G, Van Laethem JL, Le Malicot K, Sargent DJ, Laurent-Puig P, Sinicrope FA. Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy: A Pooled Analysis From 2 Randomized Clinical Trials. JAMA Oncol. 2018 Mar 1;4(3):379-383. doi: 10.1001/jamaoncol.2017.2899.
• Sinicrope FA, Shi Q, Allegra CJ, Smyrk TC, Thibodeau SN, Goldberg RM, Meyers JP, Pogue-Geile KL, Yothers G, Sargent DJ, Alberts SR. Association of DNA Mismatch Repair and Mutations in BRAF and KRAS With Survival After Recurrence in Stage III Colon Cancers : A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Oncol. 2017 Apr 1;3(4):472-480. doi: 10.1001/jamaoncol.2016.5469.
• Sticca RP, Alberts SR, Mahoney MR, Sargent DJ, Finstuen LM, Nelson GD, Husted TM, Franko J, Goldman CD, Pockaj BA. Current use and surgical efficacy of laparoscopic colectomy in colon cancer. J Am Coll Surg. 2013 Jul;217(1):56-62; discussion 62-3. doi: 10.1016/j.jamcollsurg.2013.02.023. Epub 2013 Apr 24.
• Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012 Apr 4;307(13):1383-93. doi: 10.1001/jama.2012.385.

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