Clinical trial NCT03321539: Phase Ⅲ Trial of Adjuvant Chemotherapy in Patients With N2-3 Nasopharyngeal Carcinoma
Official title: Phase Ⅲ Trial of Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (GP Versus PF) in Patients With N2-3 Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal carcinoma;adjuvant chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-10-25
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Cancer Center of Guangzhou Medical University
2. The Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital
3. The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progress-free survival(PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival(OS)
timeFrame: 3 years
measure: Locoregional failure-free survival(LRRFS)
timeFrame: 3 years
measure: Distant metastasis-free survival(DMFS)
timeFrame: 3 years
measure: Overall response rate
timeFrame: 16 weeks after completion of concurrent chemoradiotherapy
measure: Incidence of acute and late toxicity
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou,
country: China
facility: Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital
state: Guizhou
city: Changsha
country: China
facility: The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Sun Yat-sen University
name: Hai-Qiang Mai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.