TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Phase Ⅲ Trial of Induction Chemotherapy（TPF） Followed by Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy (PF) in Patients With High Risk Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03306121
• Other study ID #: 2017-FXY-034
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 13, 2017
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To see the effect of induction chemotherapy（TPF） followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy (PF) in treating patients with high risk nasopharyngeal carcinoma (NPC).

Description:

Patients presented with non-keratinizing NPC and stage AnyTN2-3M0 and plasma EBV DNA≥1500copies/ml are randomly assigned to receive TPF(paclitaxel liposome+cisplatin+5-fluorouracil) induction chemotherapy plus concurrent chemoradiotherapy (investigational arm) or concurrent chemoradiotherapy plus PF (cisplatin+5-fluorouracil) adjuvant chemotherapy (control arm). Patients in both arms receive intensity-modulated radiotherapy(IMRT), and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. Patients in the investigational arm receive paclitaxel liposome (135mg/m2 on day 1), cisplatin (25mg/m2 on day 1-3) and 5-fluorouracil (750mg/m2 civ 120h) every three weeks for three cycles before the radiotherapy. Patients in the control arm receive adjuvant cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles after the radiotherapy. The primary end point is progress-free survival (PFS). Secondary end points include overall survival(OS),locoregional failure-free survival(LRRFS), distant metastasis-free survival(DMFS), overall response rates after treatments and toxic effects(short-term and long-term). All efficacy analyses are conducted in the intention-to-treat population.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 322
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

• Original clinical staged as anyT N2-3M0(according to the American Joint Committee on Cancer(AJCC) 7th edition)and plasma EBVDNA=1500copies/ml

• 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 >65years.

• 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

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• TPF+CCRT
Patients receive paclitaxel liposome (135mg/m2 on day 1) , cisplatin (25mg/m2 on day 1-3) and 5-fluorouracil (750mg/m2 civ 120h) every three weeks for three cycles of induction chemotherapy before radiotherapy. Patients receive IMRT and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy (D1,D22,D43 of RT)
• CCRT+ PF
Patients receive cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles 4 weeks after radiotherapy. Patients receive IMRT and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy (D1,D22,D43 of RT)

Locations

Country	Name	City	State
China	Sun Yat-sen Universitty Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (5)

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 O — View Citation

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. Che — View Citation

Chen C, Wang FH, An X, Luo HY, Wang ZQ, Liang Y, Zhang L, Li YH. Triplet combination with paclitaxel, cisplatin and 5-FU is effective in metastatic and/or recurrent nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 2013 Feb;71(2):371-8. doi: 10.1007/s — View Citation

Lee AW, Tung SY, Ngan RK, Chappell R, Chua DT, Lu TX, Siu L, Tan T, Chan LK, Ng WT, Leung TW, Fu YT, Au GK, Zhao C, O'Sullivan B, Tan EH, Lau WH. Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasophar — View Citation

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, Tan — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress-free survival(PFS)	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.	3 years
Secondary	Overall survival(OS)	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.	3 years
Secondary	Locoregional failure-free survival(LRRFS)	The LRRFS 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.	3 years
Secondary	Distant metastasis-free survival(DMFS)	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.	3 years
Secondary	Overall response rate	Tumour response was classified according to RECIST, version 1.1	16 weeks after completion of IMRT
Secondary	Incidence of acute and late toxicity	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.	3 years