The Role of Induction Chemotherapy for High-risk Locally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether Intensity-modulated radiation therapy (IMRT) combined inductive and concurrent chemotherapy with more intensive regimen (cisplatin and paclitaxel) is feasible and effective than current standard treatment for high-risk locally advanced NPC patients.

Detailed Description
-----------------
Meta-analysis showed chemotherapy when combined with conventional radiotherapy in locally advanced naso-pharyngeal carcinoma can improve 5-year overall survival with 6%, and beyond all concurrent chemotherapy with cisplatin benefits most. However, from Lin's (Lin JC, 2004) study, locally advanced NPC with high risk factors can not benefit from conventional concurrent chemoradiation. Failure pattern analysis revealed that local and distant failure accounted for 50% respectively. Large-scale data has demonstrated that with IMRT, local control can achieve 90%. Previous studies showed inductive chemotherapy can decrease distant metastasis. We need more effective and stronger chemotherapy, and we still need to testify concurrent chemotherapy combined with inductive chemotherapy. A prospective trial would thus provide valuable information to help physicians and patients more precisely identify the feasibility and effectiveness of inductive + concurrent chemotherapy combined with IMRT for high-risk locally advanced NPC.

Official Title
-----------------
Phase 2 Study of Inductive Plus Concurrent Chemoradiation Versus Concurrent Plus Adjuvant Chemoradiation for High-risk Locally Advanced Nasopharyngeal Carcinoma in the Era of IMRT

Conditions
-----------------
Nasopharyngeal Neoplasms

Intervention / Treatment
-----------------
* Drug: Cisplatin
* Drug: Paclitaxel
* Radiation: IMRT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: biopsy-proved NPC N3 or T4N2 or multiple lymphnodes involved with at least one mass 4 cm or more in maximal diameter according to 7th UICC Staging provide written informed consent Kps>70 no dostant metastasis Life expectancy≥6 months Adequate renal function, defined as follows: Serum creatinine < 2 x institutional upper limitof normal(ULN) within 2 weeks prior to registration or; creatinine clearance rate (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined by 24- hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CCrmale) The following assessments are required within 2 weeks prior to the start of registration: Na, K, Cl, glucose, Ca, Mg, and albumin. Exclusion Criteria: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Severe, active co-morbidity

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: Inductive + concurrent chemotherapy<br>Inductive chemotherapy :paclitaxel 175mg/m2 d1+ cisplatin 80mg/m2d1, every 21 days for two cycles concurrent chemotherapy:cisplatin 80mg/m2 on week 1, 4, 7 radiotherapy: IMRT | Drug: Cisplatin<br>* induction: Cisplatin: 80mg/m2, d1 and d22 concurrent: Cisplatin: 100mg/m2, d1, 22, 43 adjuvant: cisplatin: 75mg/m2, d1, d22, d43,d64<br>Drug: Paclitaxel<br>* induction: paclitaxel 175mg/m2 d1,d22 adjuvant: paclitaxel 175mg/m2 d1,d22, d43,d64<br>Radiation: IMRT<br>* 69.96Gy-73.43Gy to gross tumor volume, 60Gy to high-risk clinincal target volume, 50Gy to lower risk clincial target volume<br>* Other names: intensity-modulated radiotherapy;|
| Active Comparator: concurrent + adjuvant chemotherapy<br>concurrent chemotherapy: cisplatin 80 mg/m2, on week 1, 4, 7 adjuvant chemotherapy: paclitaxel 175mg/m2 + cisplatin 75mg/m2, every 21 days for 4 cycles radiotherapy: IMRT | Drug: Cisplatin<br>* induction: Cisplatin: 80mg/m2, d1 and d22 concurrent: Cisplatin: 100mg/m2, d1, 22, 43 adjuvant: cisplatin: 75mg/m2, d1, d22, d43,d64<br>Drug: Paclitaxel<br>* induction: paclitaxel 175mg/m2 d1,d22 adjuvant: paclitaxel 175mg/m2 d1,d22, d43,d64<br>Radiation: IMRT<br>* 69.96Gy-73.43Gy to gross tumor volume, 60Gy to high-risk clinincal target volume, 50Gy to lower risk clincial target volume<br>* Other names: intensity-modulated radiotherapy;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant failure free survival |  | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | three years | 
| acute treatment toxicity |  | up to 16 weeks | 
| late treatment toxicity |  | three years | 
| Local recurrence rate |  | three years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adjuvants, inductive, concurrent, chemoradiotherapy, high-risk, locally advanced, NPC