Cisplatin-based and Carboplatin-based Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma

NPC Clinical Trial

Official title:

Intensity-modulated Radiation Therapy Combined With Cisplatin-based or Carboplatin-based Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma：: A Phase 3 Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03919552
• Other study ID #: NFEC-2018-013
• Status: Recruiting
• Phase: Phase 3
• Start date: January 31, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2023
• Source: Nanfang Hospital of Southern Medical University
• Contact: Jian Guan, Ph.D.
• Phone: +86-13632102247
• Email: 51643930[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare cisplatin-based with carboplatin-based chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of carboplatin-based chemoradiotherapy in NPC patients.

Description:

Patients presented with non-keratinizing NPC and stage T3-4NxM0/TxN2-3M0 are randomly assigned to receive cisplatin-based (control arm) with carboplatin-based (investigational arm) chemoradiotherapy. Patients in the investigational arm receive docetaxel (75mg/m2 on day 1), carboplatin (AUC 4 on day 1) every three weeks for two cycles before the radiotherapy, and then receive radical radiotherapy and carboplatin (AUC 5 on day 1) every three weeks for three cycles during radiotherapy. Patients in the control arm receive docetaxel (75mg/m2 on day 1), cisplatin (75mg/m2 on day 1) every three weeks for two cycles before the radiotherapy, and then receive radical radiotherapy and cisplatin (100mg/m2 on day 1) every three weeks for three cycles during radiotherapy. Patients are stratified according to stage. The primary end point is overall survival (OS). Secondary end points include failure-free survival (FFS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), initial response rates after treatments and toxic effects. All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 482
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type).

• Tumor staged as T3-4Nx/TxN2-3 (according to the 8th American Joint Commission on Cancer edition).

• No evidence of distant metastasis (M0).

• Satisfactory performance status: Karnofsky scale (KPS) > 70.

• 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 =65 years or <18 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.

Related Conditions & MeSH terms

• Carboplatin
• Carcinoma
• Cisplatin
• Nasopharyngeal Carcinoma
• NPC

Intervention

Drug:
• Docetaxel,Carboplatin
Patients receive docetaxel (75mg/m2 on day 1), carboplatin (AUC 4 on day 1) every three weeks for two cycles before the radiotherapy.
• Docetaxel,Cisplatin
Patients receive docetaxel (75mg/m2 on day 1), cisplatin (75mg/m2 on day 1) every three weeks for two cycles before the radiotherapy.

Radiation:
• Carboplatin-based concurrent chemoradiotherapy
Patients receive radical radiotherapy and carboplatin (AUC 5) every three weeks for three cycles during radiotherapy.
• Cisplatin-based concurrent chemoradiotherapy
Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.

Locations

Country	Name	City	State
China	Southern medical university	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (14)

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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. — View Citation

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Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1765-77. doi: 10.1158/1055-9965.EPI-06-0353. — View Citation

Fallai C, Bolner A, Signor M, Gava A, Franchin G, Ponticelli P, Taino R, Rossi F, Ardizzoia A, Oggionni M, Crispino S, Olmi P. Long-term results of conventional radiotherapy versus accelerated hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy in locoregionally advanced carcinoma of the oropharynx. Tumori. 2006 Jan-Feb;92(1):41-54. doi: 10.1177/030089160609200108. — View Citation

Guan J, Zhang Y, Li Q, Zhang Y, Li L, Chen M, Xiao N, Chen L. A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC). Oncotarget. 2016 Oct 25;7(43):70185-70193. doi: 10.18632/oncotarget.11824. — View Citation

Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1143-54. doi: 10.1056/NEJMra0707975. No abstract available. — View Citation

Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wunsch-Filho V, Franceschi S, Hayes RB, Herrero R, Kelsey K, Koifman S, La Vecchia C, Lazarus P, Levi F, Lence JJ, Mates D, Matos E, Menezes A, McClean MD, Muscat J, Eluf-Neto J, Olshan AF, Purdue M, Rudnai P, Schwartz SM, Smith E, Sturgis EM, Szeszenia-Dabrowska N, Talamini R, Wei Q, Winn DM, Shangina O, Pilarska A, Zhang ZF, Ferro G, Berthiller J, Boffetta P. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):541-50. doi: 10.1158/1055-9965.EPI-08-0347. Epub 2009 Feb 3. — View Citation

Klein G. Nasopharyngeal carcinoma (NPC) is an enigmatic tumor. Semin Cancer Biol. 2002 Dec;12(6):415-8. doi: 10.1016/s1044579x02000834. No abstract available. — View Citation

Munro AJ. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer. Br J Cancer. 1995 Jan;71(1):83-91. doi: 10.1038/bjc.1995.17. — View Citation

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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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival	Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first.	3-year
Secondary	Locoregional failure-free survival	Locoregional failure-free survival is calculated from randomisation to the first locoregional failure.	3-year
Secondary	Distant failure-free survival	Distant failure-free survival is calculated from randomisation to the first locoregional failure.	3-year
Secondary	The initial response rates after treatments	The initial response rates is calculated at the time 1 week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy.	A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy.
Secondary	Toxic effects	Radiation and chemotherapy related toxic effects as assessed by CTCAE v4.0.	3-year
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year