A Trial On 4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation In N2-3 Nasopharyngeal Carcinoma

NCT02512315 | Unknown Phase 3 DMC

• 1 other identifier: NACT4-NPC-5010
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 4

Brief Summary

The standard treatment strategy of locally advanced nasopharyngeal carcinoma (NPC) nowadays is concurrent chemoradiation (CCRT) based on intensity-modulated radiation therapy (IMRT). However, distant metastasis remains the major cause of treatment failure, especially in patients with T1-4N2-3M0 diseases (N2-3 NPC). The investigators inferred that it was more appropriate to consider N2-3 NPC as a systemic disease instead of a local disease. NACT of sufficient intensity such as 4 cycles might be effective enough for control of the pre-existing micrometastases. Therefore, the objective of this phase 3 multicenter randomized controlled trial is to make a comparison between NACT of 4 cycles plus CCRT based on IMRT and CCRT alone in N2-3 NPC on distant metastasis, survival and adverse reaction.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal carcinoma; Neoadjuvant chemotherapy; Concurrent chemoradiation; Distant metastasis; Survival

Outcome Measures

Primary Outcomes (2)

• 5-year overall survival (5y-OS)

  Percentage of patients in a treatment group who are alive for a 5-year period of follow-up after the date of pathologic diagnosis

  5 years after the date of pathologic diagnosis

• 5-year distant-metastasis-free survival (5y-MFS)

  Percentage of patients in a treatment group who are alive without distant metastasis for a 5-year period of follow-up after the date of pathologic diagnosis

  5 years after the date of pathologic diagnosis

Secondary Outcomes (3)

• 5-year local-relapse-free survival (5y-RFS)

  5 years after the date of pathologic diagnosis

• 5-year disease-free survival (5y-DFS)

  5 years after the date of pathologic diagnosis

• Incidence of grade 3/4 adverse event

  Once a week during therapy, up to 7 weeks (Group A) or 19 weeks (Group B)

Study Arms (2)

CCRT group (Group A)

ACTIVE COMPARATOR

Patients who are allocated into in this group will be treated with concurrent chemoradiation (CCRT).

Radiation: Concurrent chemoradiation (CCRT)

NACT-CCRT group (Group B)

EXPERIMENTAL

Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.

Drug: Docetaxel (DOC); Drug: Cisplatin (DDP); Radiation: Concurrent chemoradiation (CCRT)

Interventions

Docetaxel (DOC) DRUG

Neoadjuvant chemotherapy (NACT) is administrated every 3 weeks with the regimen comprised of docetaxel plus cisplatin. A total of 4 cycles of NACT is applied. Docetaxel is given at a dose of 75mg/m2 on the first day of every cycle.

Also known as: Docetaxel Injection

NACT-CCRT group (Group B)

Cisplatin (DDP) DRUG

Neoadjuvant chemotherapy (NACT) is administrated every 3 weeks with the regimen comprised of docetaxel plus cisplatin. A total of 4 cycles of NACT is applied. Cisplatin is given at a dose of 75mg/m2 on the first day of every cycle.

Also known as: Cisplatin Injection

NACT-CCRT group (Group B)

Concurrent chemoradiation (CCRT) RADIATION

The technology of radiotherapy is intensity-modulated radiation therapy (IMRT). A total dose of 66-72Gy is given to gross tumor of nasopharynx (GTVnx), 60-70Gy to positive neck lymph nodes (GTVnd), 60Gy to high-risk region (CTV1), and 50-54Gy to prophylactic irradiation region (CTV2). The regimen of concurrent chemotherapy is single-agent cisplatin 40mg/m2 weekly.

CCRT group (Group A); NACT-CCRT group (Group B)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathological diagnosis of nasopharyngeal carcinoma
• Union Internationale Contre le Cancer/American Joint Cancer Committee (UICC/AJCC) 2010 Stage T1-4 N2-3 M0 through magnetic resonance imaging of head and neck, whole-body bone scan and thoracoabdominal computed tomography
• Male or female with age no older than 70 years old
• Karnofsky Performance Scores ≥ 80
• Expected survival ≥ 3 months

You may not qualify if:

• Patients with distant metastasis before or during radiotherapy
• Severe dysfunction of heart, lung, liver, kidney or hematopoietic system
• Severe neurological, mental or endocrine diseases
• History of other malignancies
• Prior chemotherapy, radiotherapy or application of monoclonal antibodies
• Patients participated in clinical trials of other drugs within last 3 months
• Pregnant or lactating women
• Those who are considered by the researchers unsuitable to participate

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (4)

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, 510030, China

RECRUITING

First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Shenzhen People's Hospital

Shenzhen, Guangdong, 518020, China

RECRUITING

Related Publications (18)

• Moss WT. Therapeutic radiology, 2nd ed. St Louis, MO: Mosby; 1965: 142-180.

  BACKGROUND

• Guigay J, Temam S, Bourhis J, Pignon JP, Armand JP. Nasopharyngeal carcinoma and therapeutic management: the place of chemotherapy. Ann Oncol. 2006 Sep;17 Suppl 10:x304-7. doi: 10.1093/annonc/mdl278. No abstract available.

  PMID: 17018743 BACKGROUND

• Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. doi: 10.1200/JCO.1998.16.4.1310.

  PMID: 9552031 BACKGROUND

• Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003 Feb 15;21(4):631-7. doi: 10.1200/JCO.2003.06.158.

  PMID: 12586799 BACKGROUND

• Wee J, Tan EH, Tai BC, Wong HB, Leong SS, Tan T, Chua ET, Yang E, Lee KM, Fong KW, Tan HS, Lee KS, Loong S, Sethi V, Chua EJ, Machin D. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol. 2005 Sep 20;23(27):6730-8. doi: 10.1200/JCO.2005.16.790.

  PMID: 16170180 BACKGROUND

• 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

• J. Y. Hsiang, K. Liu, S. Iganej, et al. Concurrent chemoradiation with and without adjuvant chemotherapy in advanced stage nasopharyngeal carcinoma: A retrospective analysis. J Clin Oncol. 2004, 22(Supp 114): 5619.

  BACKGROUND

• Pignon JP, le Maitre A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 14.

  PMID: 19446902 BACKGROUND

• Tan T, Lim WT, Fong KW, Cheah SL, Soong YL, Ang MK, Ng QS, Tan D, Ong WS, Tan SH, Yip C, Quah D, Soo KC, Wee J. Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):952-60. doi: 10.1016/j.ijrobp.2015.01.002.

  PMID: 25832687 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

• Loong HH, Ma BB, Leung SF, Mo F, Hui EP, Kam MK, Chan SL, Yu BK, Chan AT. Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Radiother Oncol. 2012 Sep;104(3):300-4. doi: 10.1016/j.radonc.2011.12.022. Epub 2012 Jan 31.

  PMID: 22300609 BACKGROUND

• Honkoop AH, Luykx-de Bakker SA, Hoekman K, Meyer S, Meyer OW, van Groeningen CJ, van Diest PJ, Boven E, van der Wall E, Giaccone G, Wagstaff J, Pinedo HM. Prolonged neoadjuvant chemotherapy with GM-CSF in locally advanced breast cancer. Oncologist. 1999;4(2):106-11.

  PMID: 10337380 BACKGROUND

• da Costa Miranda V, de Souza Fede AB, Dos Anjos CH, da Silva JR, Sanchez FB, da Silva Bessa LR, de Paula Carvalho J, Filho EA, de Freitas D, Del Pilar Estevez Diz M. Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness. Gynecol Oncol. 2014 Feb;132(2):287-91. doi: 10.1016/j.ygyno.2013.12.002. Epub 2013 Dec 9.

  PMID: 24333355 BACKGROUND

• Sun XM, Huang Y, Chen CY, et al. Long-term outcomes of patients with advanced N-stage nasopharyngeal carcinoma treated by intensity-modulated radiotherapy alone or with chemotherapy. Chinese Journal of Radiation Oncology. 2013, 22(3): 225-229.

  BACKGROUND

• Ghossein RA, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res. 1999 Aug;5(8):1950-60.

  PMID: 10473071 BACKGROUND

• Lee AW, Au JS, Teo PM, Leung TW, Chua DT, Sze WM, Zee BC, Law SC, Leung SF, Tung SY, Kwong DL, Lau WH. Staging of nasopharyngeal carcinoma: suggestions for improving the current UICC/AJCC Staging System. Clin Oncol (R Coll Radiol). 2004 Jun;16(4):269-76. doi: 10.1016/j.clon.2004.01.008.

  PMID: 15214651 BACKGROUND

• Gao J, Tao YL, Li G, Yi W, Xia YF. Involvement of difference in decrease of hemoglobin level in poor prognosis of Stage I and II nasopharyngeal carcinoma: implication in outcome of radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1471-8. doi: 10.1016/j.ijrobp.2011.05.009. Epub 2011 Jun 25.

  PMID: 21708429 BACKGROUND

• Xie WH, Xiao WW, Chang H, Xu MJ, Hu YH, Zhou TC, Zhong Q, Chen CY, Lu LX, Wang QX, Zhu YJ, Yang J, Shi XY, Kang HL, Wei JW, Huang R, Peng HH, Yuan Y, Wu SH, Jiang XH, Liu YJ, Wen BX, Gao YH. Four cycles of docetaxel plus cisplatin as neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in stage N2-3 nasopharyngeal carcinoma: phase 3 multicentre randomised controlled trial. BMJ. 2025 Apr 15;389:e081557. doi: 10.1136/bmj-2024-081557.

  PMID: 40233976 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Docetaxel; Cisplatin

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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yuan-hong Gao, M.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuan-hong Gao, M.D

CONTACT

+86-13560182168; gaoyh@sysucc.org.cn

Hui Chang, M.D

CONTACT

+86-13480295989; changhui@sysucc.org.cn

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: Deputy Director of Department of Radiation Oncology, Sun Yat-sen University Cancer Center

Study Record Dates

• First Submitted: July 24, 2015
• First Posted: July 30, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 30, 2021

Record last verified: 2021-08

Locations

CN (4)