The Role of Induction Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

Study Overview
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Brief Summary
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The purpose of this study is to verify that induction gemcitabine and cisplatin plus intensity-modulated radiotherapy (IMRT) is non-inferior to concurrent weekly cisplatin plus IMRT for patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Detailed Description
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Patients with non-keratinizing NPC T1-4N2-3或T3-4N0-1M0 (UICC/AJCC 7th edition) are randomly assigned to receive induction chemotherapy or CCRT alone. Patients in experimental group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before intensity-modulated radiotherapy (IMRT). Patients in control group receive IMRT concurrently with weekly cisplatin 40 mg/m² up to 7cycles. IMRT is given as 2.0-2.33 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor. Our primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Official Title
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A Randomized Trial Comparing Induction Gemcitabine and Cisplatin Plus Intensity-modulated Radiotherapy With Concurrent Cisplatin Plus Intensity-modulated Radiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: cisplatin
* Drug: cisplatin
* Radiation: Intensity-modulated Radiotherapy


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或T3-4N0-1M0 (according to the 7th AJCC edition). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL. Adequate liver function: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤1.5×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. Treatment with palliative intent. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period). History of previous RT (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: Experimental<br>Induction chemotherapy+IMRT gemcitabine and cisplatin regimen Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT). | Drug: Gemcitabine<br>* Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.<br>Drug: cisplatin<br>* Experimental arm: Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 2 cycles before IMRT.<br>* Other names: DDP;Radiation: Intensity-modulated Radiotherapy<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor.<br>* Other names: IMRT;|
| Active Comparator: Active Comparator<br>IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with weekly cisplatin 40 mg/m² up to 7cycles. | Drug: cisplatin<br>* Active Comparator arm: Patients receive weekly cisplatin 40 mg/m² up to 7cycles during IMRT.<br>* Other names: DDP;Radiation: Intensity-modulated Radiotherapy<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.33 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor.<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival | Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 2 years | 
| Locoregional failure-free survival | Locoregional failure-free survival is calculated from randomization to the first locoregional failure. | 2 years | 
| Distant failure-free survival | Distant failure-free survival is calculated from randomization to the first remote failure. | 2 years | 
| Overall response rate | Overall response rate at 3 months after completion of IMRT | 3 months after completion of IMRT | 
| Number of participants with adverse events | Incidence of acute and late toxicity | 2 years | 
| Quality of life during treatment | Quality of life is measured by FACIT questionnaire. | During whole chemotherapy and IMRT treatment.For experimental arm, an expected average of 12 weeks; for active comparator arm, an expected average of 6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasopharyngeal carcinoma, induction chemotherapy