Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in IC + CCRT for Locoregionally Advanced NPC

NCT03503136 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2018-FXY-076
• Study Type: interventional
• Target: 632
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 3, multicentre, non-inferiority, randomised factorial trial. The purpose of this study is to study the efficacy and safety of nedaplatin versus cisplatin, and capecitabine versus fluorouracil in induction docetaxel, cisplatin, and fluorouracil (TPF) plus concurrent chemoradiotherapy with cisplatin (P-RT) in locoregionally advanced nasopharyngeal carcinoma (NPC).

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; Induction chemotherapy; Concurrent chemoradiotherapy; Nedaplatin; Capecitabine

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival is calculated from the date of randomisation to the date of disease progression or death from any cause, whichever is first.

  3 years

Secondary Outcomes (5)

• Overall survival

  3 years

• Distant failure-free survival

  3 years

• Locoregional failure-free survival

  3 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (acute toxicity) and RTOG/EORTC (late toxicity)

  Up to 3 years

• Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30

  Up to 16 weeks

Study Arms (4)

A (TPF+P-RT)

EXPERIMENTAL

Induction docetaxel, cisplatin, and fluorouracil plus concurrent chemoradiotherapy with cisplatin

Drug: docetaxel, cisplatin, and fluorouracil; Drug: cisplatin

B (TNF+N-RT)

EXPERIMENTAL

Induction docetaxel, nedaplatin, and fluorouracil plus concurrent chemoradiotherapy with nedaplatin

Drug: nedaplatin; Drug: docetaxel, nedaplatin, and fluorouracil

C (TPX+P-RT)

EXPERIMENTAL

Induction docetaxel, cisplatin, and capecitabine plus concurrent chemoradiotherapy with cisplatin

Drug: cisplatin; Drug: docetaxel, cisplatin, and capecitabine

D (TNX+N-RT)

EXPERIMENTAL

Induction docetaxel, nedaplatin, and capecitabine plus concurrent chemoradiotherapy with nedaplatin

Drug: docetaxel, nedaplatin, and capecitabine; Drug: nedaplatin

Interventions

docetaxel, nedaplatin, and capecitabine DRUG

Patients receive docetaxel(60 mg/m2 on day 1), nedaplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.

Also known as: TNX induction chemotherapy

D (TNX+N-RT)

nedaplatin DRUG

Patients receive concurrent nedaplatin (100mg/m2) every three weeks for two cycles during radiotherapy.

Also known as: N

B (TNF+N-RT); D (TNX+N-RT)

docetaxel, cisplatin, and fluorouracil DRUG

Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.

Also known as: TPF induction chemotherapy

A (TPF+P-RT)

cisplatin DRUG

Patients receive concurrent cisplatin (100mg/m2) every three weeks for two cycles during radiotherapy.

Also known as: P

A (TPF+P-RT); C (TPX+P-RT)

docetaxel, cisplatin, and capecitabine DRUG

Patients receive docetaxel(60 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) and capecitabine (625 mg/m2 bid, on Days 1 to 14) every three weeks for three cycles before the radiotherapy.

Also known as: TPX induction chemotherapy

C (TPX+P-RT)

docetaxel, nedaplatin, and fluorouracil DRUG

Patients receive docetaxel (60mg/m2 on day 1), nedaplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.

Also known as: TNF induction chemotherapy

B (TNF+N-RT)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60
• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type)
• Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0 or 1
• Tumor staged as American Joint Committee on Cance (AJCC) III-IVA (except T3-4N0)
• Adequate marrow: leucocyte count ≥ 4×10\^9/L, hemoglobin ≥ 90g/L and platelet count ≥ 100×10\^9/L.
• Normal liver and renal 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; 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.
• 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.
• Patients who could not tolerate or allergic to capecitabine.
• Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Tongji Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Peking University: collaborator
• Air Force Military Medical University, China: collaborator
• Second Affiliated Hospital of Soochow University: collaborator
• The First Affiliated Hospital of Guangdong Pharmaceutical University: collaborator
• First People's Hospital of Foshan: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Cancer Hospital of Guizhou Province: collaborator
• Xiangya Hospital of Central South University: collaborator
• Jilin Provincial Tumor Hospital: collaborator
• Henan Cancer Hospital: collaborator
• Hunan Cancer Hospital: collaborator
• Cancer Hospital of Guangxi Medical University: collaborator
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: collaborator
• Zhejiang Cancer Hospital: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (9)

• Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):661-8. doi: 10.1016/j.ijrobp.2010.03.024. Epub 2010 Jul 17.

  PMID: 20643517 BACKGROUND

• Li WF, Sun Y, Mao YP, Chen L, Chen YY, Chen M, Liu LZ, Lin AH, Li L, Ma J. Proposed lymph node staging system using the International Consensus Guidelines for lymph node levels is predictive for nasopharyngeal carcinoma patients from endemic areas treated with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):249-56. doi: 10.1016/j.ijrobp.2012.09.003. Epub 2012 Nov 29.

  PMID: 23200171 BACKGROUND

• Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.

  PMID: 27686945 BACKGROUND

• Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, Qi B, Tang QN, Wang P, Li XY, Li JB, Liu Q, Gao YH, Xie FY, Liu LT, Li Y, Liu SL, Xie HJ, Liang YJ, Sun XS, Yan JJ, Wu YS, Luo DH, Huang PY, Xiang YQ, Sun R, Chen MY, Lv X, Wang L, Xia WX, Zhao C, Cao KJ, Qian CN, Guo X, Hong MH, Nie ZQ, Chen QY, Mai HQ. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2018 Apr;19(4):461-473. doi: 10.1016/S1470-2045(18)30104-9. Epub 2018 Feb 28.

  PMID: 29501366 BACKGROUND

• Sasaki Y, Tamura T, Eguchi K, Shinkai T, Fujiwara Y, Fukuda M, Ohe Y, Bungo M, Horichi N, Niimi S, et al. Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin. Cancer Chemother Pharmacol. 1989;23(4):243-6. doi: 10.1007/BF00451649.

  PMID: 2647312 BACKGROUND

• Zheng J, Wang G, Yang GY, Wang D, Luo X, Chen C, Zhang Z, Li Q, Xu W, Li Z, Wang D. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Jpn J Clin Oncol. 2010 May;40(5):425-31. doi: 10.1093/jjco/hyp183. Epub 2010 Jan 19.

  PMID: 20085903 BACKGROUND

• Tang C, Wu F, Wang R, Lu H, Li G, Liu M, Zhu H, Zhu J, Zhang Y, Hu K. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial. Am J Cancer Res. 2016 Sep 1;6(9):2064-2075. eCollection 2016.

  PMID: 27725911 BACKGROUND

• 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.

  PMID: 25529384 BACKGROUND

• Chen SZ, Chen XM, Ding Y, Wang XC, Zhang F, Mo KL. Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis. Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1114-8.

  PMID: 21764676 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Docetaxel; nedaplatin; Capecitabine; Cisplatin; Fluorouracil

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Principal Investigator Principal Investigator, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Ma, M.D.

CONTACT

+86-20-87343469; majun2@mail.sysu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 19, 2018
• Study Start: June 1, 2018
• Primary Completion: June 1, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 11, 2018

Record last verified: 2018-05

Locations

CN (1)