The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

NCT02460887 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: Sun Yat-sen University HPY
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to verify that induction gemcitabine and cisplatin plus intensity-modulated radiotherapy (IMRT) is non-inferior to concurrent weekly cisplatin plus IMRT for patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Conditions

Nasopharyngeal Carcinoma

Keywords

nasopharyngeal carcinoma; induction chemotherapy

Outcome Measures

Primary Outcomes (1)

• Failure-free survival

  Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first.

  2 years

Secondary Outcomes (6)

• Overall survival

  2 years

• Locoregional failure-free survival

  2 years

• Distant failure-free survival

  2 years

• Overall response rate

  3 months after completion of IMRT

• Number of participants with adverse events

  2 years

Study Arms (2)

Experimental

EXPERIMENTAL

Induction chemotherapy+IMRT gemcitabine and cisplatin regimen Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT).

Drug: Gemcitabine; Drug: cisplatin; Radiation: Intensity-modulated Radiotherapy

Active Comparator

ACTIVE COMPARATOR

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with weekly cisplatin 40 mg/m² up to 7cycles.

Drug: cisplatin; Radiation: Intensity-modulated Radiotherapy

Interventions

Gemcitabine DRUG

Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.

Experimental

cisplatin DRUG

Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.

Also known as: DDP

Experimental

Intensity-modulated Radiotherapy RADIATION

Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor.

Also known as: IMRT

Active Comparator; Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma (including WHO II or III).
• Tumor staged as T1-4N2-3或T3-4N0-1M0 (according to the 7th AJCC edition).
• Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
• Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL.
• Adequate liver function: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤1.5×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.

You may not qualify if:

• WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
• Treatment with palliative intent.
• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (12)

• 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.

  PMID: 22154591 BACKGROUND

• 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.

  PMID: 19064973 BACKGROUND

• Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013 Mar;14(3):257-64. doi: 10.1016/S1470-2045(13)70011-1. Epub 2013 Feb 13.

  PMID: 23414589 BACKGROUND

• Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, Brockstein BE, Agulnik MB, Mittal BB, Yunus F, Samant S, Raez LE, Mehra R, Kumar P, Ondrey F, Marchand P, Braegas B, Seiwert TY, Villaflor VM, Haraf DJ, Vokes EE. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014 Sep 1;32(25):2735-43. doi: 10.1200/JCO.2013.54.6309. Epub 2014 Jul 21.

  PMID: 25049329 BACKGROUND

• Fountzilas G, Ciuleanu E, Bobos M, Kalogera-Fountzila A, Eleftheraki AG, Karayannopoulou G, Zaramboukas T, Nikolaou A, Markou K, Resiga L, Dionysopoulos D, Samantas E, Athanassiou H, Misailidou D, Skarlos D, Ciuleanu T. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol. 2012 Feb;23(2):427-35. doi: 10.1093/annonc/mdr116. Epub 2011 Apr 27.

  PMID: 21525406 BACKGROUND

• Yi J, Huang X, Gao L, Luo J, Zhang S, Wang K, Qu Y, Xiao J, Xu G. Intensity-modulated radiotherapy with simultaneous integrated boost for locoregionally advanced nasopharyngeal carcinoma. Radiat Oncol. 2014 Feb 18;9:56. doi: 10.1186/1748-717X-9-56.

  PMID: 24533569 BACKGROUND

• Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan;61(1):33-8. doi: 10.1007/s00280-007-0441-8. Epub 2007 Mar 20.

  PMID: 17909810 BACKGROUND

• He X, Ou D, Ying H, Zhu G, Hu C, Liu T. Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1027-33. doi: 10.1007/s00405-011-1669-9. Epub 2011 Jun 26. Erratum In: Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1035. Xiayun, He [corrected to He, Xiayun].

  PMID: 21706324 BACKGROUND

• Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong Nasopharyngeal Cancer Study Group. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1;23(28):6966-75. doi: 10.1200/JCO.2004.00.7542.

  PMID: 16192584 BACKGROUND

• Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002 Apr 15;20(8):2038-44. doi: 10.1200/JCO.2002.08.149.

  PMID: 11956263 BACKGROUND

• Lee AW, Lau KY, Hung WM, Ng WT, Lee MC, Choi CW, Chan CC, Tung R, Cheng PT, Yau TK. Potential improvement of tumor control probability by induction chemotherapy for advanced nasopharyngeal carcinoma. Radiother Oncol. 2008 May;87(2):204-10. doi: 10.1016/j.radonc.2008.02.003. Epub 2008 Mar 10.

  PMID: 18329742 BACKGROUND

• Xu T, Hu C, Zhu G, He X, Wu Y, Ying H. Preliminary results of a phase III randomized study comparing chemotherapy neoadjuvantly or concurrently with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Med Oncol. 2012 Mar;29(1):272-8. doi: 10.1007/s12032-010-9803-x. Epub 2011 Jan 30.

  PMID: 21279704 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Pei-Yu Huang, M. D., Ph.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 3, 2015
• Study Start: June 1, 2015
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Locations

CN (1)