Induction Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT01245959
• Recruitment Status: Unknown
• First Posted: November 23, 2010
• Last Update Posted: February 13, 2014
• Sponsor: Sun Yat-sen University
• Collaborators: Fudan University; West China Hospital; Huazhong University of Science and Technology; Peking University Cancer Hospital & Institute; Zhejiang Cancer Hospital; Central South University; Jiangsu Cancer Institute & Hospital; First People's Hospital of Foshan; The Third Affiliated Hospital of Harbin Medical University; Cancer Hospital of Guangxi Medical University; Jiangxi Provincial Cancer Hospital; Guangzhou Medical University
• Information provided by (Responsible Party): Jun Ma, Sun Yat-sen University

Tracking Information

• First Submitted Date: November 22, 2010
• First Posted Date: November 23, 2010
• Last Update Posted Date: February 13, 2014
• Study Start Date: January 2011
• Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2012)

Failure-free survival [ Time Frame: 3-year ]

Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first.

Original Primary Outcome Measures (submitted: November 22, 2010)

Failure-free survival [ Time Frame: 2-year ]

Failure-free survival is calculated from the date of randomization to the date of the first failure at any site.

Current Secondary Outcome Measures (submitted: August 9, 2012)

• Overall survival [ Time Frame: 3-year ]
  Overall survival is calculated from randomization to death from any cause.
• Locoregional failure-free survival [ Time Frame: 3-year ]
  The latency (ie, time from randomisation) to the first locoregional failure
• Distant failure-free survival [ Time Frame: 3-year ]
  The latency (ie, time from randomisation) to the first remote failure
• The initial response rates after treatments [ Time Frame: A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy ]
• Toxic effects [ Time Frame: During and after treatment ]

Original Secondary Outcome Measures (submitted: November 22, 2010)

Overall survival, locoregional failure-free survival and distant failure-free survival [ Time Frame: 2-year ]

Overall survival is calculated from randomization to death from any cause. For locoregional failure-free survival and distant failure-free survival analyses, the latencies to the first local or remote failure, respectively, are recorded.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Induction Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Official Title: Prospective Randomized Trial Comparing Induction Chemotherapy Plus Concurrent Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Brief Summary: The purpose of this study is to compare induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of induction chemotherapy in NPC patients.
• Detailed Description: Patients presented with non-keratinizing NPC and stage T3-4N1M0/TxN2-3M0 are randomly assigned to receive induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy (investigational arm) or concurrent chemoradiotherapy (control arm). Patients in both arms receive radical radiotherapy, and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. Patients in the investigational arm receive docetaxel(60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy. Patients are stratified according to the treatment centers and stage. The primary end point is failure-free survival (FFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), initial response rates after treatments and toxic effects. All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nasopharyngeal Carcinoma

Intervention

• Drug: Docetaxel, cisplatin and fluorouracil
  Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.
  Other Name: TPF induction chemotherapy
• Radiation: Concurrent chemoradiotherapy
  Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.
  Other Name: Radical radiotherapy and concurrent cisplatin

Study Arms

• Experimental: Induction chemotherapy and concurrent chemoradiotherapy
  Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy, and then receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.
  Interventions:

  • Drug: Docetaxel, cisplatin and fluorouracil
  • Radiation: Concurrent chemoradiotherapy
• Active Comparator: Concurrent chemoradiotherapy
  Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.
  Intervention: Radiation: Concurrent chemoradiotherapy

Publications *

• Cancer incidence in five continents. Volume VIII. IARC Sci Publ. 2002;(155):1-781. No abstract available.
• Stephen B. Edge, David R. Byrd, Carolyn C. Compton, April G. Fritz, Frederick L. Greene, and Andy Trotti. AJCC Cancer Staging Manual. 7th ed. New York: Springer, 2009: 41-46.
• Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):661-8. doi: 10.1016/j.ijrobp.2010.03.024. Epub 2010 Jul 17.
• Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):47-56. doi: 10.1016/j.ijrobp.2005.06.037.
• Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. doi: 10.1056/NEJMoa071028.
• Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. doi: 10.1056/NEJMoa070956.
• Qin-Hua Zhang, Wei Luo, Qi-Chao Zhou, Zhan Yu, Jun Ma, Meng-Zhong Liu. TPF induction chemotherapy followed by intensity-modulated radiotherapy and concomitant chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Chinese Journal of Cancer Prevention and Treatment 16(8): 625-628, 2009.
• Guo L, Lin HX, Xu M, Chen QY, Wang CT, Huang PY. Phase I study of TPF neoadjuvant chemotherapy followed by radical radiotherapy in advanced nasopharyngeal carcinoma. Chin J Cancer. 2010 Feb;29(2):136-9. doi: 10.5732/cjc.009.10367.
• Friedman J, Furberg, C, DeMets D. Fundamentals of clinical trials. New York: Springer-Verlag; 1998.
• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. doi: 10.1016/0360-3016(95)00060-C. No abstract available.
• Chow, S.C., Shao, J., Wang, H. Sample Size Calculations in Clinical Research. New York: Marcel Dekker; 2003.
• Dong D, Zhang F, Zhong LZ, Fang MJ, Huang CL, Yao JJ, Sun Y, Tian J, Ma J, Tang LL. Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959). BMC Med. 2019 Oct 23;17(1):190. doi: 10.1186/s12916-019-1422-6.
• Zhang Y, Li WF, Liu X, Chen L, Sun R, Sun Y, Liu Q, Ma J. Nomogram to predict the benefit of additional induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Analysis of a multicenter, phase III randomized trial. Radiother Oncol. 2018 Oct;129(1):18-22. doi: 10.1016/j.radonc.2017.12.002. Epub 2017 Dec 16.
• Li WF, Chen L, Sun Y, Ma J. Induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Chin J Cancer. 2016 Nov 15;35(1):94. doi: 10.1186/s40880-016-0157-4.
• Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 9, 2012): 476
• Original Estimated Enrollment (submitted: November 22, 2010): 362
• Estimated Study Completion Date: April 2018
• Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type).
• Tumor staged as T3-4N1/N2-3 (according to the 7th American Joint Commission on Cancer edition).
• No evidence of distant metastasis (M0).
• Satisfactory performance status: Karnofsky scale (KPS) > 70.
• Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L and platelet count ≥100000/μL.
• Normal liver function test: Alanine Aminotransferase (ALT)、Aspartate Aminotransferase (AST) <1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤2.5×ULN, and bilirubin ≤ULN.
• Adequate renal function: creatinine clearance ≥60 ml/min.
• Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

• WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
• Age ≥60 years or <18 years.
• Treatment with palliative intent.
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
• Pregnancy or lactation.
• History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
• Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
• Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01245959
• Other Study ID Numbers: YP2010171
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jun Ma, Sun Yat-sen University
• Original Responsible Party: Jun Ma, Sun Yat-sen University Cancer Center
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

Collaborators

• Fudan University
• West China Hospital
• Huazhong University of Science and Technology
• Peking University Cancer Hospital & Institute
• Zhejiang Cancer Hospital
• Central South University
• Jiangsu Cancer Institute & Hospital
• First People's Hospital of Foshan
• The Third Affiliated Hospital of Harbin Medical University
• Cancer Hospital of Guangxi Medical University
• Jiangxi Provincial Cancer Hospital
• Guangzhou Medical University

Investigators

• Study Chair: Jun Ma, M.D.; Sun Yat-sen University

• PRS Account: Sun Yat-sen University
• Verification Date: January 2014