Chronomodulated Chemotherapy Followed by Concurrent Chemo-radiotherapy With IMRT in the Treatment of Advanced Nasopharyngeal Cancer

Study Overview
=================
Brief Summary
-----------------
Observe and compare the chrono-chemotherapy IMRT and conventional chemotherapy and intensity modulated radiotherapy term efficacy of the treatment of locally advanced nasopharyngeal carcinoma. Evaluation chrono-chemotherapy IMRT and conventional chemotherapy and intensity modulated radiotherapy in locally advanced nasopharyngeal carcinoma safety and tolerability. 3）observing the adverse reaction and effects of two groups,expected chrono-chemotherapy group can achieve lower toxicity, improve the curative effect, for the treatment of nasopharyngeal carcinoma provides a more reasonable way.

Official Title
-----------------
Multi-center Phase II Clinical Randomized Study of Chronomodulated Chemotherapy Followed by Concurrent Chemo-radiotherapy With IMRT in the Treatment of Advanced Nasopharyngeal Cancer

Conditions
-----------------
Esophageal Neoplasms

Intervention / Treatment
-----------------
* Device: Chrono-chemotherapy pump:Melodie
* Device: Routine intravenous drip
* Drug: induction Chrono-chemotherapy
* Drug: induction Routine-chemotherapy
* Drug: cisplatin chrono-chemotherapy
* Drug: cisplatin routine-chemotherapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: initial treatment of advanced nasopharyngeal carcinoma Ⅲ-Ⅳ patients with pathologically confirmed (according to 2010 UICC staging, T3-4, N0-3), without evidence of distant metastasis (M0). Have measurable tumor lesions. KPS≥70 points. the age of 18-70 years old, male or female. no major organ dysfunction; normal bone marrow function (WBC ≥4.0 × 109 / L, platelets ≥100 × 109 / L, hemoglobin ≥90g / L), normal liver function (total bilirubin, alanine aminotransferase, aspartate aminotransferase ≤1.5 times the upper limit of normal), normal renal function (creatinine ≤ 1.5 times upper limit of normal). understand this study and signed informed consent. Exclusion Criteria: distant metastasis. who had received prior chemotherapy. patients have physical or mental illness, and by researchers believe that patients can not be completely or fully understood in this study possible complications. pregnancy (via the urine or serum β-HCG test confirmed) or during lactation. serious complications, such as uncontrolled hypertension, heart failure, diabetes and so on.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melodie group<br>Induction chrono-chemotherapy followed by cisplatin chrono-chemotherapy concurrent combined with intensity-modulated radiation therapy | Device: Chrono-chemotherapy pump:Melodie<br> <br> Drug: induction Chrono-chemotherapy<br> <br> Drug: cisplatin chrono-chemotherapy<br> <br> Radiation: intensity-modulated radiation therapy<br> <br> |
| Other: Routine-Chemotherapy<br>Induction routine-chemotherapy followed by cisplatin routine-chemotherapy concurrent combined with intensity-modulated radiation therapy | Device: Routine intravenous drip<br> <br> Drug: induction Routine-chemotherapy<br> <br> Drug: cisplatin routine-chemotherapy<br> <br> Radiation: intensity-modulated radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with curative effect | Evaluate the immediate effect at 1year after Concurrent chemo-radiotherapy by RECIST. | 1 year | 
| Number of Participants with Adverse Events as a Measure of Safety | To assess and record nausea, vomiting, oral mucositis, diarrhea and other adverse drug reactions by CTC 3.0. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Evaluate the Progression-free survival at five years after Concurrent chemo-radiotherapy by RECIST. | 5 years | 
| Overall survival | Evaluate the Overall survival at five years after Concurrent chemo-radiotherapy by RECIST. | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronomodulated Chemotherapy, Intensity Modulated Radiation Therapy, Advanced Nasopharyngeal Cancer