Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in IC + CCRT for Locoregionally Advanced NPC

Nasopharyngeal Carcinoma Clinical Trial

— NX-NPC  

Official title:

Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Locoregionally Advanced NPC： a Phase 3, Multicentre, Non-inferiority, Randomised Factorial Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03503136
• Other study ID #: 2018-FXY-076
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2018
• Est. completion date: June 2026

Study information

• Verified date: May 2018
• Source: Sun Yat-sen University
• Contact: Jun Ma, M.D.
• Phone: +86-20-87343469
• Email: majun2[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, multicentre, non-inferiority, randomised factorial trial. The purpose of this study is to study the efficacy and safety of nedaplatin versus cisplatin, and capecitabine versus fluorouracil in induction docetaxel, cisplatin, and fluorouracil (TPF) plus concurrent chemoradiotherapy with cisplatin (P-RT) in locoregionally advanced nasopharyngeal carcinoma (NPC).

Description:

In this study, patients with non-keratinizing NPC and staged III-IVA (except T3-4N0) are randomly assigned to one of the four groups: Group A: TPF+P-RT; Group B: TNF+N-RT; Group C: TPX+P-RT; Group D: TNX+N-RT. In induction chemotherapy, patients will receive docetaxel(60 mg/m2 on day 1), cisplatin or nedaplatin (60 mg/m2 on day 1) and fluorouracil (600 mg/m2 on Days 1 to 5) or capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radical radiotherapy. Concurrent cisplatin or nedaplatin (100mg/m2 on day 1) was given every three weeks for two cycles during radiotherapy. Patients are stratified according to the treatment centers and stage. The primary endpoint is progression-free survival (PFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), toxic effects, and quality of life (QOL). 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: Not yet recruiting
• Enrollment: 632
• Est. completion date: June 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age 18-60

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type)

• Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0 or 1

• Tumor staged as American Joint Committee on Cance (AJCC) III-IVA (except T3-4N0)

• Adequate marrow: leucocyte count = 4×10^9/L, hemoglobin = 90g/L and platelet count = 100×10^9/L.

• Normal liver and renal 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; 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.

• 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.

• Patients who could not tolerate or allergic to capecitabine.

• Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus.

Related Conditions & MeSH terms

• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• docetaxel, nedaplatin, and capecitabine
Patients receive docetaxel(60 mg/m2 on day 1), nedaplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.
• nedaplatin
Patients receive concurrent nedaplatin (100mg/m2) every three weeks for two cycles during radiotherapy.
• 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.
• cisplatin
Patients receive concurrent cisplatin (100mg/m2) every three weeks for two cycles during radiotherapy.
• docetaxel, cisplatin, and capecitabine
Patients receive docetaxel(60 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.
• docetaxel, nedaplatin, and fluorouracil
Patients receive docetaxel (60mg/m2 on day 1), nedaplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.

Locations

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

Sponsors (17)

Lead Sponsor

Collaborator

Sun Yat-sen University

Affiliated Tumor Hospital of Guangzhou Medical University, Cancer Hospital of Guangxi Medical University, Cancer Hospital of Guizhou Province, Fifth Affiliated Hospital, Sun Yat-Sen University, First People's Hospital of Foshan, Fourth Military Medical University, Henan Cancer Hospital, Hunan Cancer Hospital, Jilin Provincial Tumor Hospital, Peking University, Second Affiliated Hospital of Soochow University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Tongji Hospital, Wuhan Union Hospital, China, Xiangya Hospital of Central South University, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (9)

Chen SZ, Chen XM, Ding Y, Wang XC, Zhang F, Mo KL. Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis. Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1114-8. — 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

Lee AW, Ngan RK, Tung SY, Cheng A, Kwong DL, Lu TX, Chan AT, Chan LL, Yiu H, Ng WT, Wong F, Yuen KT, Yau S, Cheung FY, Chan OS, Choi H, Chappell R. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer. 2015 Apr 15;121(8):1328-38. doi: 10.1002/cncr.29208. Epub 2014 Dec 19. — View Citation

Li WF, Sun Y, Mao YP, Chen L, Chen YY, Chen M, Liu LZ, Lin AH, Li L, Ma J. Proposed lymph node staging system using the International Consensus Guidelines for lymph node levels is predictive for nasopharyngeal carcinoma patients from endemic areas treated with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):249-56. doi: 10.1016/j.ijrobp.2012.09.003. Epub 2012 Nov 29. — View Citation

Sasaki Y, Tamura T, Eguchi K, Shinkai T, Fujiwara Y, Fukuda M, Ohe Y, Bungo M, Horichi N, Niimi S, et al. Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin. Cancer Chemother Pharmacol. 1989;23(4):243-6. — View Citation

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. — View Citation

Tang C, Wu F, Wang R, Lu H, Li G, Liu M, Zhu H, Zhu J, Zhang Y, Hu K. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial. Am J Cancer Res. 2016 Sep 1;6(9):2064-2075. eCollection 2016. — View Citation

Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, Qi B, Tang QN, Wang P, Li XY, Li JB, Liu Q, Gao YH, Xie FY, Liu LT, Li Y, Liu SL, Xie HJ, Liang YJ, Sun XS, Yan JJ, Wu YS, Luo DH, Huang PY, Xiang YQ, Sun R, Chen MY, Lv X, Wang L, Xia WX, Zhao C, Cao KJ, Qian CN, Guo X, Hong MH, Nie ZQ, Chen QY, Mai HQ. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2018 Apr;19(4):461-473. doi: 10.1016/S1470-2045(18)30104-9. Epub 2018 Feb 28. — View Citation

Zheng J, Wang G, Yang GY, Wang D, Luo X, Chen C, Zhang Z, Li Q, Xu W, Li Z, Wang D. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Jpn J Clin Oncol. 2010 May;40(5):425-31. doi: 10.1093/jjco/hyp183. Epub 2010 Jan 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Progression-free survival is calculated from the date of randomisation to the date of disease progression or death from any cause, whichever is first.	3 years
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3 years
Secondary	Distant failure-free survival	Distant failure-free survival is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit.	3 years
Secondary	Locoregional failure-free survival	Locoregional failure-free survival is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit.	3 years
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (acute toxicity) and RTOG/EORTC (late toxicity)	Incidence of acute and late toxicity	Up to 3 years
Secondary	Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30	QOL was assessed by EORTC QLQ-C30 during the treatment period	Up to 16 weeks