Adjuvant Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT00677118
• Recruitment Status: Unknown
• First Posted: May 13, 2008
• Last Update Posted: July 12, 2013
• Sponsor: Sun Yat-sen University
• Collaborators: Fudan University; Zhejiang Cancer Hospital; Huazhong University of Science and Technology; Fifth Affiliated Hospital, Sun Yat-Sen University; Peking University Cancer Hospital & Institute; Guangdong Provincial People's Hospital
• Information provided by: Sun Yat-sen University

Tracking Information

• First Submitted Date: May 9, 2008
• First Posted Date: May 13, 2008
• Last Update Posted Date: July 12, 2013
• Study Start Date: June 2006
• Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2011)

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

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

• Original Primary Outcome Measures (submitted: May 9, 2008): disease free survival [ Time Frame: 2-yr ]

Current Secondary Outcome Measures (submitted: May 9, 2011)

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

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

• Original Secondary Outcome Measures (submitted: May 9, 2008): Overall survival [ Time Frame: 2-yr ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adjuvant Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Official Title: A Multicenter Prospective Randomized Trial Comparing Concurrent Chemoradiotherapy Plus Adjuvant Chemotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Brief Summary: The purpose of this study is to compare concurrent chemoradiotherapy plus adjuvant chemotherapy with concurrent chemoradiotherapy in patients with locoregionally advanced NPC, in order to evaluate the value of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients.
• Detailed Description: Patients presented with non-keratinizing NPC and stage T3-4N1M0/TxN2-3M0 are randomly assigned to receive concurrent chemoradiotherapy plus adjuvant chemotherapy (investigational arm)or concurrent chemoradiotherapy (control arm). Patients in both arms receive radical radiotherapy and cisplatin (40mg/m2 on day 1) weekly during radiotherapy. Patients in the investigational arm receive cisplatin (80mg/m2 on day 1) and fluorouracil (800mg/m2 on Day 1 to 5) every four weeks for three cycles after completion of radiotherapy. Patients are stratified according to the treatment centers. The primary end point was failure-free survival (FFS). Secondary end points included overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), the initial response rates after treatments, toxic effects and treatment compliance. All efficacy analyses were conducted in the intention-to-treat population; the safety population included only patients who received 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: Cisplatin,fluorouracil
  Patients receive radical radiotherapy and cisplatin (40mg/m2 on day 1) weekly during radiotherapy, then receive cisplatin (80mg/m2 on day 1) and fluorouracil (800mg/m2 on Day 1 to 5) every four weeks for three cycles after completion of radiotherapy.
  Other Name: Cisplatin and fluorouracil
• Drug: Cisplatin
  Patients receive radical radiotherapy and cisplatin (40mg/m2 on day 1) weekly during radiotherapy.

Study Arms

• Experimental: Concurrent and adjuvant
  Concurrent chemoradiotherapy plus adjuvant chemotherapy
  Intervention: Drug: Cisplatin,fluorouracil
• Active Comparator: Concurrent
  Concurrent chemoradiotherapy
  Intervention: Drug: Cisplatin

Publications *

• Chua DT, Sham JS, Kwong DL, Au GK. Treatment outcome after radiotherapy alone for patients with Stage I-II nasopharyngeal carcinoma. Cancer. 2003 Jul 1;98(1):74-80. doi: 10.1002/cncr.11485.
• Ma J, Mai HQ, Hong MH, Cui NJ, Lu TX, Lu LX, Mo HY, Min HQ. Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations? Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1181-9. doi: 10.1016/s0360-3016(01)01537-1.
• Zhao C, Han F, Lu LX, Huang SM, Lin CG, Deng XW, Lu TX, Cui NJ. [Intensity modulated radiotherapy for local-regional advanced nasopharyngeal carcinoma]. Ai Zheng. 2004 Nov;23(11 Suppl):1532-7. Chinese.
• Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C, Akazawa P, Weinberg V, Fu KK. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):12-22. doi: 10.1016/s0360-3016(02)02724-4.
• Kam MK, Teo PM, Chau RM, Cheung KY, Choi PH, Kwan WH, Leung SF, Zee B, Chan AT. Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1440-50. doi: 10.1016/j.ijrobp.2004.05.022.
• Decker DA, Drelichman A, Al-Sarraf M, Crissman J, Reed ML. Chemotherapy for nasopharyngeal carcinoma. A ten-year experience. Cancer. 1983 Aug 15;52(4):602-5. doi: 10.1002/1097-0142(19830815)52:43.0.co;2-6.
• Al-Sarraf M. Chemotherapeutic management of head and neck cancer. Cancer Metastasis Rev. 1987;6(3):181-98. doi: 10.1007/BF00144263.
• Rossi A, Molinari R, Boracchi P, Del Vecchio M, Marubini E, Nava M, Morandi L, Zucali R, Pilotti S, Grandi C, et al. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study. J Clin Oncol. 1988 Sep;6(9):1401-10. doi: 10.1200/JCO.1988.6.9.1401.
• Chi KH, Chang YC, Guo WY, Leung MJ, Shiau CY, Chen SY, Wang LW, Lai YL, Hsu MM, Lian SL, Chang CH, Liu TW, Chin YH, Yen SH, Perng CH, Chen KY. A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1238-44. doi: 10.1016/s0360-3016(01)02781-x.
• Frederick L. Greene, David L. Page, Irvin D. Fleming, et al: American Joint Committee on Cancer Staging Manual (ed 6). Philadelphia (PA): Lippincott, 2002.
• Freedman J, Furberg, C, DeMets D. Fundamentals of clinical trials. Springer-Verlag, NY, 1998.
• Chow, S.C., Shao, J., Wang, H. Sample Size Calculations in Clinical Research. New York: Marcel Dekker; 2003.
• Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:150-158. doi: 10.1016/j.ejca.2017.01.002. Epub 2017 Feb 22.
• Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 9, 2008): 506
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2015
• Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing carcinoma (according to World Health Organization (WHO) histologically type)
2. Tumor staged as N2-3or T3-4N1 (according to 6th American Joint Committee on Cancer staging system)
3. No evidence of distant metastasis (M0)
4. Performance status: KPS ≥70
5. With normal liver function test (Alanine Aminotransferase、Aspartate Aminotransferase ≤2.5×upper limit of normal)
6. Renal: creatinine clearance ≥60ml/min
7. Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥80g/L and platelet count ≥100000/μL
8. Written informed consent

Exclusion Criteria:

1. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
2. Age ≥70 or <18
3. With a history of renal disease
4. Prior malignancy
5. Previous chemotherapy or radiotherapy
6. Patient is pregnant or lactating
7. Unstable cardiac disease requiring treatment.
8. Emotion disturbance

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 69 Years (Adult, Older 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: NCT00677118
• Other Study ID Numbers: YP2008004
• 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 Cancer Center
• Original Responsible Party: Sun Yat-sen University
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

Collaborators

• Fudan University
• Zhejiang Cancer Hospital
• Huazhong University of Science and Technology
• Fifth Affiliated Hospital, Sun Yat-Sen University
• Peking University Cancer Hospital & Institute
• Guangdong Provincial People's Hospital

Investigators

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

• PRS Account: Sun Yat-sen University
• Verification Date: March 2010