TPF Induction Chemotherapy vs PF Adjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced NPC

Study Overview
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Brief Summary
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Through randomized controlled phase III multicenter clinical trials, TPF induction chemotherapy vs. PF regimen adjuvant chemotherapy concurrently Radiotherapy and chemotherapy for the treatment of locally advanced nasopharyngeal carcinoma: the efficacy, toxicity and quality of life, and further improvement Survival rate and improve the quality of life.

Official Title
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A Multicenter, Randomized Controlled Phase III Clinical Trial of TPF Induction Chemotherapy Versus PF Adjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Conditions
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Locally Advanced 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 (according to World Health Organization (WHO) histologically type). Clinical staged as III，IVa（according to the American Joint Committee on Cancer(AJCC) 7th edition） Fertility women should ensure contraception during entry into the study. Age 18-69 years old. 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: With distant metastasis. who had received prior chemotherapy or radiotherapy. patients have physical or mental illness, and by researchers believe that patients 4.can not be completely or fully understood in this study possible complications. 5.pregnancy (via the urine or serum β-HCG test confirmed) or during lactation. 6.serious complications, such as uncontrolled hypertension, heart failure, diabetes and so on.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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>TPF neoadjuvant chemotherapy followed by cisplatin chemotherapy concurrent combined with intensity-modulated radiation therapy | Drug: TPF+CCRT<br>* Patients receive Neoadjuvant Docetaxel (75mg/m2 on day1 03:30-04:30) and cisplatin (75mg/m2 on day 1-5 10:00-22:00) and 5-FU(750mg/m2 on day 1-5 22:00-10:00) every 21days for three cycles followed by concurrent cisplatin (100mg/m2 on day1 10:00-22:00)every 21 days for three cycles during radiotherapy<br>* Other names: Experimental group;|
| Other: CCRE+PF<br>Cisplatin chemotherapy concurrent combined with intensity-modulated radiation therapy followed by PF adjuvant chemotherapy | Drug: CCRT+PF<br>* Patients receive concurrent cisplatin (100mg/m2 on day1 10:00-22:00)every 21 days for three cycles during radiotherapy followed by adjuvant cisplatin (80mg/m2 on day 1-5 10:00-22:00) and 5-FU(800mg/m2 on day 1-5 22:00-10:00) every 21days for three cycles<br>* Other names: Control group;|

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(year) 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(year) 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(LRFS) | The LRFS(year) 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(year) 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(CR/PR/SD/PD) was classified according to RECIST v1.1 | 12 weeks after completion of concurrent chemoradiotherapy | 
| Incidence of acute and late toxicity | Incidence of acute toxicity（Grade1/2/3/4） 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 |