Clinical trial NCT03306121: TPF+CCRT vs.CCRT+PF in High Risk Nasopharyngeal Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal carcinoma;Induction chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-10-10
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progress-free survival(PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival(OS)
timeFrame: 3 years
measure: Locoregional failure-free survival(LRRFS)
timeFrame: 3 years
measure: Distant metastasis-free survival(DMFS)
timeFrame: 3 years
measure: Overall response rate
timeFrame: 16 weeks after completion of IMRT
measure: Incidence of acute and late toxicity
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Universitty Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen Universitty Cancer Center
name: Hai-Qiang Mai, MD,PhD
role: STUDY_CHAIR
References:
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