Induction Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Prospective Randomized Trial Comparing Induction Chemotherapy Plus Concurrent Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01245959
• Other study ID #: YP2010171
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 22, 2010
• Last updated: February 12, 2014
• Start date: January 2011
• Est. completion date: April 2018

Study information

• Verified date: January 2014
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 476
• Est. completion date: April 2018
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

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.

Radiation:
• Concurrent chemoradiotherapy
Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (13)

Lead Sponsor

Collaborator

Sun Yat-sen University

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

Country where clinical trial is conducted

China, 

References & Publications (12)

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. Review. — View Citation

Cancer incidence in five continents. Volume VIII. IARC Sci Publ. 2002;(155):1-781. — View Citation

Chow, S.C., Shao, J., Wang, H. Sample Size Calculations in Clinical Research. New York: Marcel Dekker; 2003.

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. — View Citation

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. — View Citation

Friedman J, Furberg, C, DeMets D. Fundamentals of clinical trials. New York: Springer-Verlag; 1998.

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. — View Citation

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. — View Citation

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. — View Citation

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.

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.

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival	Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first.	3-year	No
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year	No
Secondary	Locoregional failure-free survival	The latency (ie, time from randomisation) to the first locoregional failure	3-year	No
Secondary	Distant failure-free survival	The latency (ie, time from randomisation) to the first remote failure	3-year	No
Secondary	The initial response rates after treatments		A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy	No
Secondary	Toxic effects		During and after treatment	Yes