Phase Ⅲ Trial of Adjuvant Chemotherapy in Patients With N2-3 Nasopharyngeal Carcinoma

Overview

To see the effect if a combination of concurrent chemoradiotherapy followed by different adjuvant chemotherapy in treating patients with N2-3 nasopharyngeal carcinoma(NPC).

Full Title of Study: “Phase Ⅲ Trial of Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (GP Versus PF) in Patients With N2-3 Nasopharyngeal Carcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 25, 2022

Detailed Description

This phase Ⅲ trial is studying how well radiation therapy and chemotherapy work in treating patients with newly diagnosed N2-3 nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and fluorouracil or cisplatin and gemcitabine, work in different ways (concurrent chemoradiotherapy followed by different adjuvant chemotherapy) to stop the growth of tumor cells.

Interventions

  • Drug: CCRT+GP
    • Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated-radiotherapy (IMRT) followed by adjuvant gemcitabine (1000mg/m2 on day 1 and day 8) and cisplatin (80mg/m2 on day 1) every 21 days for three cycles 4 weeks after radiotherapy.
  • Drug: CCRT+PF
    • Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during Intensity modulated-radiotherapy (IMRT) followed by adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every 28 days for three cycles 4 weeks after radiotherapy.

Arms, Groups and Cohorts

  • Experimental: CCRT+GP
    • Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during radiotherapy followed by adjuvant gemcitabine (1000mg/m2 on day 1 and day 8) and cisplatin (80mg/m2 on day 1) every 21days for three cycles
  • Active Comparator: CCRT+PF
    • Patients receive concurrent cisplatin 100mg/m2 every 21 days for three cycles during radiotherapy followed by adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every 28 days for three cycles

Clinical Trial Outcome Measures

Primary Measures

  • Progress-free survival(PFS)
    • Time Frame: 3 years
    • Progress-free survival is calculated from the date of randomization to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up.

Secondary Measures

  • Overall survival(OS)
    • Time Frame: 3 years
    • The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up.
  • Locoregional failure-free survival(LRRFS)
    • Time Frame: 3 years
    • The LRFS 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.
  • Distant metastasis-free survival(DMFS)
    • Time Frame: 3 years
    • The DMFS 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.
  • Overall response rate
    • Time Frame: 16 weeks after completion of concurrent chemoradiotherapy
    • Tumour response was classified according to RECIST, version 1.1
  • Incidence of acute and late toxicity
    • Time Frame: 3 years
    • Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme

Participating in This Clinical Trial

Inclusion Criteria

  • Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type). – Original clinical staged as any T、N2-3M0(according to the American Joint Committee on Cancer(AJCC) 7th edition) – No evidence of distant metastasis (M0). – Age 18-65 years old. – ECOG Performance status less or equal to 1. – 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 <18 or >65 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Hai-Qiang Mai,MD,PhD, Professor – Sun Yat-sen University
  • Overall Official(s)
    • Hai-Qiang Mai, MD,PhD, Principal Investigator, Sun Yat-sen University

References

Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.

Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23. Erratum In: Lancet. 2016 Oct 15;388(10054):1882.

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.

Twu CW, Wang WY, Chen CC, Liang KL, Jiang RS, Wu CT, Shih YT, Lin PJ, Liu YC, Lin JC. Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid. Int J Radiat Oncol Biol Phys. 2014 May 1;89(1):21-9. doi: 10.1016/j.ijrobp.2014.01.052.

Citations Reporting on Results

Ribassin-Majed L, Marguet S, Lee AWM, Ng WT, Ma J, Chan ATC, Huang PY, Zhu G, Chua DTT, Chen Y, Mai HQ, Kwong DLW, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol. 2017 Feb 10;35(5):498-505. doi: 10.1200/JCO.2016.67.4119. Epub 2016 Dec 5.

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