GP vs PF as Induction Chemotherapy Combined With CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to compare the survival and toxicity of GP (gemcitabine and cisplatin) vs. PF (cisplatin and fluorouracil) as induction chemotherapy combined with concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma( NPC ) patients.

Detailed Description
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Patients presented with non-keratinizing NPC and stage T1-4N2-3/T4N0-1M0 are randomly assigned to receive GP (gemcitabine and cisplatin) or PF (cisplatin and fluorouracil) induction chemotherapy combined with concurrent chemoradiotherapy. Patients in both arms receive radical radiotherapy, and cisplatin (100mg/m²) every three weeks for two cycles during radiotherapy. Patients in the investigational arm receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles. Patients in the control arm receive fluorouracil (800mg/m² d1-5) and cisplatin (80mg/m² d1) every 3 weeks for three cycles. Our primary endpoint is progress-free survival (PFS). Secondary end points include distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRRFS), initial response rates after treatments, toxic effects and quality of life (QoL).

Official Title
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GP vs PF as Induction Chemotherapy Combined With CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma：a Prospective,Parallel, Randomized, Open Labeled, Multicenter Phase III Clinical Trial

Conditions
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Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms, Nasopharyngeal Diseases, Head and Neck Neoplasm

Intervention / Treatment
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* Drug: gemcitabine and cisplatin
* Drug: cisplatin and fluorouracil
* Radiation: IMRT
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III Tumor staged as T1-4N2-3/T4N0-1M0（according to the 8th AJCC edition） Male and no pregnant female Age between 18-65 Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L and platelet count ≥100000/μL Normal liver function test: Alanine Aminotransferase (ALT)、Aspartate Aminotransferase (AST) <2.0×upper limit of normal (ULN) Adequate renal function: creatinine clearance ≥60 ml/min Satisfactory performance status: Karnofsky scale (KPS) ≥ 70 Without radiotherapy or chemotherapy Patients must give signed informed consent Exclusion Criteria: Evidence of relapse or distant metastasis History of prior malignancy or previous treatment for NPC 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. Pregnancy or lactation

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: gemcitabine and cisplatin<br>Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles. | Drug: gemcitabine and cisplatin<br>* Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before concurrent chemoradiotherapy.<br>* Other names: gemcitabine and cisplatin (GP);Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 30～33 fraction with five daily fractions per week for 6-7 weeks to a total dose of 68～70 Gy to the primary tumor<br>Drug: cisplatin<br>* IMRT concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles.<br>* Other names: cisplatin（DDP）;|
| Active Comparator: cisplatin and fluorouracil<br>Patients receive fluorouracil (800mg/m² d1-5) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles. | Drug: cisplatin and fluorouracil<br>* Patients receive fluorouracil (800mg/m2 d1-5) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before concurrent chemoradiotherapy.<br>* Other names: cisplatin and fluorouracil (PF);Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 30～33 fraction with five daily fractions per week for 6-7 weeks to a total dose of 68～70 Gy to the primary tumor<br>Drug: cisplatin<br>* IMRT concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles.<br>* Other names: cisplatin（DDP）;|

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. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 Relapse-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 | 
| Number of participants with adverse events | Incidence of acute and late toxicity | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gemcitabine, cisplatin, fluorouracil