Induction Gemcitabine and Cisplatin in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Prospective Randomized Trial Comparing Concurrent Chemoradiotherapy With or Without Induction Gemcitabine and Cisplatin in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01872962
• Other study ID #: B2013-022-01
• Status: Active, not recruiting
• Phase: Phase 3
• First received: May 31, 2013
• Last updated: April 20, 2018
• Start date: November 2013
• Est. completion date: November 2020

Study information

• Verified date: April 2018
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare induction chemotherapy (gemcitabine+cisplatin) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma(NPC), in order to confirm the value of induction chemotherapy in NPC patients.

Description:

Patients Patients with non-keratinizing NPC T3-4N1M0/TxN2-3M0 (UICC/AJCC 7th edition) are randomly assigned to receive induction chemotherapy plus CCRT or CCRT alone. Patients in both groups receive cisplatin 100 mg/m² every 3 weeks for 3 cycles, concurrently with intensity-modulated radiotherapy (IMRT). IMRT is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor. The induction chemotherapy plus CCRT group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. Our primary endpoint is failure-free survival(FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 480
• Est. completion date: November 2020
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).

• Tumor staged as T3-4N1/N2-3 (according to the 7th AJCC 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 > 65 or < 18.

• Treatment with palliative intent.

• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.

• Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).

• History of previous RT (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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• gemcitabine and cisplatin (Induction chemotherapy)
Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before concurrent chemoradiotherapy.

Radiation:
• IMRT and concurrent cisplatin
Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor, concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.

Locations

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

Sponsors (14)

Lead Sponsor

Collaborator

Sun Yat-sen University

Cancer Hospital of Guangxi Medical University, Cancer Hospital of Guizhou Province, Cancer Hospital of Shantou University, Fifth Affiliated Hospital, Sun Yat-Sen University, First People's Hospital of Foshan, Fudan University, Jiangxi Provincial Cancer Hospital, Peking University, Tongji Hospital, West China Hospital, Wuhan Union Hospital, China, Xijing hospital of The fourth military medical university, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (21)

Barton-Burke M. Gemcitabine: a pharmacologic and clinical overview. Cancer Nurs. 1999 Apr;22(2):176-83. Review. — View Citation

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

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

Chua DT, Sham JS, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S, Vootiprux V, Cheirsilpa A, Azhar T, Reksodiputro AH. Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Cancer. 1998 Dec 1;83(11):2270-83. — View Citation

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

Edge SB, Byrd DR, Compton CC, et al: AJCC Cancer Staging Manual (ed 7th). New York, Springer, 2010

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

Foo KF, Tan EH, Leong SS, Wee JT, Tan T, Fong KW, Koh L, Tai BC, Lian LG, Machin D. Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type. Ann Oncol. 2002 Jan;13(1):150-6. — View Citation

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

Hareyama M, Sakata K, Shirato H, Nishioka T, Nishio M, Suzuki K, Saitoh A, Oouchi A, Fukuda S, Himi T. A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma. Cancer. 2002 Apr 15;94(8):2217-23. — View Citation

He X, Ou D, Ying H, Zhu G, Hu C, Liu T. Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1027-33. doi: 10.1007/s00405-011-1669-9. Epub 2011 Jun 26. Erratum in: Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1035. Xiayun, He [corrected to He, Xiayun].. — View Citation

International Nasopharynx Cancer Study Group; VUMCA I Trial. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):463-9. — View Citation

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134. — View Citation

Jiang Y, Wei YQ, Luo F, Zou LQ, Liu JY, Peng F, Huang MJ, He QM. Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study. Cancer Invest. 2005;23(2):123-8. — 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

Langendijk JA, Leemans CR, Buter J, Berkhof J, Slotman BJ. The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol. 2004 Nov 15;22(22):4604-12. — View Citation

Ma BB, Tannock IF, Pond GR, Edmonds MR, Siu LL. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002 Dec 15;95(12):2516-23. — View Citation

Ma J, Mai HQ, Hong MH, Min HQ, Mao ZD, Cui NJ, Lu TX, Mo HY. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 2001 Mar 1;19(5):1350-7. — View Citation

Ngan RK, Yiu HH, Lau WH, Yau S, Cheung FY, Chan TM, Kwok CH, Chiu CY, Au SK, Foo W, Law CK, Tse KC. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002 Aug;13(8):1252-8. — View Citation

Yau TK, Lee AW, Wong DH, Yeung RM, Chan EW, Ng WT, Tong M, Soong IS. Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma. Head Neck. 2006 Oct;28(10):880-7. — View Citation

Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan;61(1):33-8. Epub 2007 Mar 20. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival	Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first.	3-year
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year
Secondary	Locoregional failure-free survival	Locoregional failure-free survival is calculated from randomization to the first locoregional failure.	3-year
Secondary	Distant failure-free survival	Distant failure-free survival is calculated from randomization to the first remote failure.	3-year
Secondary	Number of participants with adverse events	Incidence of acute and late toxicity	up to 3 years