Concurrent Chemoradiotherapy With Nimotuzumab for High Risk Nasopharyngeal Carcinoma

Summary

This is the first phase II randomized clinical trial of concurrent chemoradiotherapy with or without EGFR blocker Nimotuzumab for high risk advanced nasopharyngeal carcinoma(NPC) , determining whether concurrent chemoradiotherapy(CCRT) combined with nimotuzumab can improve the survival rate of high-risk patients and may provide new evidence for individualized comprehensive treatment of locally advanced NPC.

Timeline

Start

2020-01-31

Primary completion

2024-08-31

Completion

2026-12

Outcome

Missed primary endpoint

paper in the CCRT-alone group (hazard ratio, 0.93 [90% CI, 0.63-1.37]; p = 0.70). PMID 41916997 ↗

paper These findings indicate that adding nimotuzumab to CCRT does not improve survival in patients with LA-NPC with a suboptimal response to IC PMID 41916997 ↗

Publications

• Background Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong Nasopharyngeal Cancer Study Group. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1;23(28):6966-75. doi: 10.1200/JCO.2004.00.7542.
• Background Ribassin-Majed L, Marguet S, Lee AWM, Ng WT, Ma J, Chan ATC, Huang PY, Zhu G, Chua DTT, Chen Y, Mai HQ, Kwong DLW, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol. 2017 Feb 10;35(5):498-505. doi: 10.1200/JCO.2016.67.4119. Epub 2016 Dec 5.
• Background Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.
• Background Bossi P, Orlandi E, Bergamini C, Locati LD, Granata R, Mirabile A, Parolini D, Franceschini M, Fallai C, Olmi P, Quattrone P, Potepan P, Gloghini A, Miceli R, Mattana F, Scaramellini G, Licitra L. Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer. Ann Oncol. 2011 Nov;22(11):2495-2500. doi: 10.1093/annonc/mdq783. Epub 2011 Mar 11.
• Background Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
• Background Chan AT, Lo YM, Zee B, Chan LY, Ma BB, Leung SF, Mo F, Lai M, Ho S, Huang DP, Johnson PJ. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst. 2002 Nov 6;94(21):1614-9. doi: 10.1093/jnci/94.21.1614.
• Background Hou X, Zhao C, Guo Y, Han F, Lu LX, Wu SX, Li S, Huang PY, Huang H, Zhang L. Different clinical significance of pre- and post-treatment plasma Epstein-Barr virus DNA load in nasopharyngeal carcinoma treated with radiotherapy. Clin Oncol (R Coll Radiol). 2011 Mar;23(2):128-33. doi: 10.1016/j.clon.2010.09.001. Epub 2010 Oct 12.
• Background Liu LT, Tang LQ, Chen QY, Zhang L, Guo SS, Guo L, Mo HY, Zhao C, Guo X, Cao KJ, Qian CN, Zeng MS, Bei JX, Hong MH, Shao JY, Sun Y, Ma J, Mai HQ. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):862-9. doi: 10.1016/j.ijrobp.2015.08.003. Epub 2015 Aug 7.
• Background Huang CL, Sun ZQ, Guo R, Liu X, Mao YP, Peng H, Tian L, Lin AH, Li L, Shao JY, Sun Y, Ma J, Tang LL. Plasma Epstein-Barr Virus DNA Load After Induction Chemotherapy Predicts Outcome in Locoregionally Advanced Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):355-361. doi: 10.1016/j.ijrobp.2019.01.007. Epub 2019 Jan 23.
• Background Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001 Oct;7(10):2958-70.
• Background Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol. 2002 Sep 15;20(18 Suppl):1S-13S. No abstract available.
• Background Chua DT, Nicholls JM, Sham JS, Au GK. Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):11-20. doi: 10.1016/j.ijrobp.2003.10.038.
• Background Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, Arvind AS. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009 Jan-Feb;1(1):41-8. doi: 10.4161/mabs.1.1.7509.
• Background Huang JF, Zhang FZ, Zou QZ, Zhou LY, Yang B, Chu JJ, Yu JH, Zhang HW, Yuan XP, Tai GM, Liu FJ, Ma CC. Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial. Oncotarget. 2017 Jan 10;8(2):2457-2465. doi: 10.18632/oncotarget.13899.
• Background Wang F, Sun Q, Jiang C, Liu T, Rihito A, Masoto S, Wang Y, Fu Z, Chen M. Additional induction chemotherapy to concurrent chemotherapy and intensity-modulated radiotherapy with or without nimotuzumab in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: a propensity score matched analysis. J Cancer. 2018 Jan 1;9(3):594-603. doi: 10.7150/jca.20461. eCollection 2018.
• Background Liu ZG, Zhao Y, Tang J, Zhou YJ, Yang WJ, Qiu YF, Wang H. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis. Oncotarget. 2016 Apr 26;7(17):24429-35. doi: 10.18632/oncotarget.8225.
• Background Fangzheng W, Chuner J, Zhiming Y, Tongxin L, Fengqin Y, Lei W, Bin L, Fujun H, Ming C, Weifeng Q, Zhenfu F. Long-Term Use of Nimotuzumab in Combination With Intensity-Modulated Radiotherapy and Chemotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma: Experience of a Single Institution. Oncol Res. 2018 Mar 5;26(2):277-287. doi: 10.3727/096504017X15079846743590. Epub 2017 Oct 18.
• Liu LT, Sun XS, Quan TT, Li XY, Guo L, Mo HY, Guo SS, Liu SL, Huang Y, Luo DH, Sun R, Jia GD, Li JB, Liu Q, Wang P, Liang YJ, Chen J, Li YF, Cheng H, Xia WX, Qiu F, Yang JH, Yang Q, Wen DX, Yan JJ, Zhao C, Chen QY, Tang LQ, Mai HQ. Concurrent chemoradiotherapy plus nimotuzumab versus chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma with a suboptimal response to induction chemotherapy: a randomized phase 2 trial. Nat Commun. 2026 Mar 31;17(1):4631. doi: 10.1038/s41467-026-71019-5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nimotuzumab	Monoclonal antibody	200 mg	—
Background	Cisplatin	Other / unclassified	100 mg/m2	—

Indications