Combination of Cisplatin Plus Gemcitabine Induction Chemotherapy and Intensity-modulated radiotherapyIntensity-modulated Radiotherapy With or Without Concurrent Cisplatin for NPC

Study Overview
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Brief Summary
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Concurrent cisplatin-based chemotherapy plus radiotherapy increased the risk of treatment-related death and severe acute toxicity. The survival benefit of adding concurrent chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma is unclear. Gemcitabine plus cisplatin chemotherapy combine with radiotherapy was effective and well tolerated by patients with locoregionally advanced NPC.

Detailed Description
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The purpose of this study is to compare gemcitabine plus cisplatin induction chemotherapy combine intensity-modulated radiotherapy with or without concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to reevaluate the value of concurrent cisplatin when 4 cycles induction chemotherapy (gemcitabine+cisplatin) and IMRT is used.

Official Title
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Combination of Cisplatin Plus Gemcitabine Induction Chemotherapy and Intensity-modulated Radiotherapy With or Without Concurrent Cisplatin for Locoregionally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Inductive chemotherapy + concurrent cisplatin and IMRT
* Drug: Inductive chemotherapy + IMRT


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 2005) histologically type). A Karnofsky performance status of at least 80; Tumor staged is according to the 7th American Joint Commission on Cancer edition as Stage III：T1-2N2M0, T3N0-2M0 Stage IVa：T4N0-2M0 Stage IVb：Any T、N3. Adequate marrow: a WBC ≥3.5×109 l-1; a platelet count ≥100×109 l-1; and hemoglobin levels ≥100 g/l. 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: a creatinine clearance rate of at least 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. Age >65 years or <18 years. Distant metastasis, Treatment with palliative intent. Pregnancy or lactation. a history of previous radiotherapy in the nasopharyngeal region or previous chemotherapy. history of renal disease, unstable cardiac disease requiring treatment.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IInductive chemotherapy + concurrent cisplatin and IMRT<br>Patients receive Gemcitabine (800mg/m2 on day 1,8) and cisplatin (80mg/m2 on day 1)of a 21 day cycle, patients received four cycles chemotherapy before the radiotherapy, then receive radical radiotherapy with IMRT and cisplatin (30 mg/m2，on day 1) repeated every weeks for 6 cycles during radiotherapy. | Drug: Inductive chemotherapy + concurrent cisplatin and IMRT<br>* Patients receive Gemcitabine (800mg/m2 on day 1,8) and cisplatin (80mg/m2 on day 1)of a 21 day cycle, patients received four cycles chemotherapy before the radiotherapy, then receive radical radiotherapy with IMRT and cisplatin (30mg/m2，on day 1) repeated every week for 6 cycles during radiotherapy.<br>* Other names: Gemcitabine and cisplatin;|
| Experimental: Inductive chemotherapy + IMRT<br>Patients receive Gemcitabine (800mg/m2 on day 1,8) and cisplatin (80mg/m2 on day 1)of a 21 day cycle, patients received four cycles chemotherapy before the radiotherapy, then receive radical radiotherapy with IMRT. | Drug: Inductive chemotherapy + IMRT<br>* Patients receive Gemcitabine (800mg/m2 on day 1,8) and cisplatin (80mg/m2 on day 1)of a 21 day cycle, patients received four cycles chemotherapy before the radiotherapy, then receive radical radiotherapy with IMRT.<br>* Other names: Gemcitabine and cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 3-year | 
| Failure-free survival | Failure-free survival is calculated from the date of randomization to the date of the first failure at any site. | 3-year | 
| Locoregional failure-free survival | the latency to the first local failure | 3-year | 
| Distant failure-free survival | The latency to the first remote failure | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the complete response rates between the two treatment arms |  | 12 weeks after the completion of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cisplatin, neoadjuvant chemotherapy, intensity-modulated radiation therapy, concurrent chemoradiotherapy