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

• ClinicalTrials.gov Identifier: NCT03321539
• Recruitment Status: Active, not recruiting
• First Posted: October 25, 2017
• Last Update Posted: May 22, 2023
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Tracking Information

• First Submitted Date: July 6, 2017
• First Posted Date: October 25, 2017
• Last Update Posted Date: May 22, 2023
• Actual Study Start Date: October 30, 2017
• Actual Primary Completion Date: December 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2017)

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.

Original Primary Outcome Measures (submitted: October 22, 2017)

Progress-free survival(PFS) [ Time Frame: 3-year ]

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.

Current Secondary Outcome Measures (submitted: November 8, 2017)

• 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

Original Secondary Outcome Measures (submitted: October 22, 2017)

• Overall survival(OS) [ Time Frame: 3-year ]
  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(LRFS) [ Time Frame: 3-year ]
  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-year ]
  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.
• Complete Response (CR) [ Time Frame: After the completion of the chemoradiotherapy treatment (up to 12 weeks) ]
  CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the chemoradiotherapy treatment. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only.
• Short-term toxic effects assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) [ Time Frame: 3 months ]
  The shortterm toxic effects were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).
• Long-term toxicities [ Time Frame: Through study completion, an average of half year ]
  QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Nasopharyngeal Carcinoma

Intervention

• 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.
  Other Name: Adjuvant GP
• 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.
  Other Name: Adjuvant PF

Study Arms

• 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
  Intervention: Drug: CCRT+GP
• 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
  Intervention: Drug: CCRT+PF

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 22, 2017): 216
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Actual Primary Completion Date: December 25, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03321539
• Other Study ID Numbers: 2017-FXY-077
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University
• Original Responsible Party: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University, Professor and Deputy Director
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Hai-Qiang Mai, MD,PhD; Sun Yat-sen University

• PRS Account: Sun Yat-sen University
• Verification Date: May 2023