Effect of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy in High Risk Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Randomized Phase 3 Trial of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy Versus Concurrent Chemotherapy Alone in High Risk Nasopharyngeal Carcinoma Patients Treated With Intensity-modulated Radiotherapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02621970
• Other study ID #: 2015-FXY-098-Dept. of RT
• Status: Not yet recruiting
• Phase: Phase 3
• First received: December 2, 2015
• Last updated: December 2, 2015
• Start date: January 2016
• Est. completion date: January 2024

Study information

• Verified date: December 2015
• Source: Sun Yat-sen University
• Contact: Fang-Yun Xie, M.D.
• Phone: +86-020-87342618
• Email: xiefy[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Interventional

Clinical Trial Summary

The investigators aim to evaluate the survival benefit from triple combination of induction, concurrent and aduvant chemotherapy versus concurrent chemotherapy alone for high risk locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

Description:

All eligible patients receive intensity-modulated radiotherapy (IMRT) with a total dose of 68 to 70 Gy in 33 fractions to the primary tumor. Patients in the experimental arm receive triple therapy of induction, concurrent and adjuvant chemotherapy. Induction chemotherapy consists of docetaxel 75 mg/m², D1 and cisplatin 25 mg/m², D1-3 every 3 weeks for 2 cycles. Concurrent chemotherapy in the experimental arm consists of cisplatin 25 mg/m², D1-3 every 3 weeks and Xeloda 2000mg/m², D1-14 for 3 cycles. Adjuvant chemotherapy consists of Xeloda 2500mg/m², D1-14 for 2 cycles. Concurrent chemotherapy in the control arm consists of cisplatin 100 mg/m², D1 every 3 weeks for 3 cycles.The primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence of grade 3 or higher acute toxicities. 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: 534
• Est. completion date: January 2024
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma.

• Tumor staged as T4N0-3M0 or T1-3N3M0 (the 2010 UICC/AJCC staging system).

• Pretreatment EBV DNA = 4000 copies/mL.

• Karnofsky scale (KPS) = 70.

• Adequate marrow: leucocyte count = 4×10E9/L, hemoglobin = 110g/L and platelet count = 100×10E9/L.

• Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin = 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) = 2.5×ULN.

• Adequate renal function: creatinine clearance = 60 ml/min or creatinine = 1.5×ULN.

• Patients must give written informed consent.

Exclusion Criteria:

• 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 radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume).

• Prior radiotherapy, 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.

• Dihydropyrimidine dehydrogenase deficiency.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Cisplatin 1
Cisplatin 25 mg/m2, D1-3
• Cisplatin 2
Cisplatin 100 mg/m2, D1
• Docetaxel
Docetaxel 60mg/m2, D1
• Xeloda
Xeloda 2000mg/m2, D1-14 in concurrent chemotherapy and Xeloda 2500mg/m2, D1-14 in adjuvant chemotherapy

Radiation:
• Intensity-modulated radiotherapy
Intensity-modulated radiotherapy

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
Sun Yat-sen University	Affiliated Tumor Hospital of Guangzhou Medical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View Citation

Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, Yu BK, Chiu SK, Kwan WH, Ho R, Chan I, Ahuja AT, Zee BC, Chan AT. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009 Jan 10;27(2):242-9. doi: 10.1200/JCO.2008.18.1545. Epub 2008 Dec 8. — 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

Wu F, Wang R, Lu H, Wei B, Feng G, Li G, Liu M, Yan H, Zhu J, Zhang Y, Hu K. Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: treatment outcomes of a prospective, multicentric clinical study. Radiother Oncol. 2014 Jul;112(1):106-11. doi: 10.1016/j.radonc.2014.05.005. Epub 2014 Jun 2. — View Citation

Zhang LN, Gao YH, Lan XW, Tang J, OuYang PY, Xie FY. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study. Oral Oncol. 2015 Oct;51(10):950-6. doi: 10.1016/j.oraloncology.2015.07.004. Epub 2015 Jul 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	failure-free survival		Two year	Yes
Secondary	overall survival		two year	Yes
Secondary	distant metastasis-free survival		two year	Yes
Secondary	locoregional relapse-free survival		two year	Yes
Secondary	Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0		two months	Yes