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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: TPF+CCRT
* Drug: CCRT+ PF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPF+CCRT<br>Patients receive induction chemotherapy with 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 radiotherapy, then followed by concurrent IMRT and cisplatin (100mg/m2) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) . | Drug: TPF+CCRT<br>* 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)<br>* Other names: TPF induction chemotherapy;|
| Active Comparator: CCRT+ PF<br>Patients receive concurrent IMRT and cisplatin (100mg/m2) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) , then followed by three cycles of adjuvant chemotherapy with cisplatin (80mg/m2 on day 1) and 5-fluorouracil (1000mg/m2 civ 96h) every four weeks for three cycles four weeks after radiotherapy. | Drug: CCRT+ PF<br>* 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)<br>* Other names: Adjuvant PF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Overall response rate | Tumour response was classified according to RECIST, version 1.1 | 16 weeks after completion of IMRT | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma;Induction chemotherapy