Concurrent Docetaxel Plus Cisplatin or Cisplatin Alone With IMRT in High Risk Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
The investigators aim to evaluate the efficiency and toxicities of concurrent docetaxel and cisplatin with intensity-modulated radiotherapy in high risk locoregionally advanced nasopharyngeal carcinoma.

Detailed Description
-----------------
Eligible patients are randomly assigned to receive intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy of docetaxel plus cisplatin or cisplatin alone. IMRT is delivered with a total dose of 68 Gy or higher in 33 fractions to the primary tumor. Concurrent chemotherapy in the experimental arm consists of docetaxel 60 mg/m², D1 and cisplatin 25 mg/m², D1-3 every 3 weeks for 3 cycles. Concurrent chemotherapy in the control arm consists of cisplatin 100 mg/m², D1 every 3 weeks for 3 cycles.The primary endpoint is overall survival (OS), defined as time from randomization to the day of death from any cause. Secondary end points include failure-free survival (FFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence of grade 3 or higher acute toxicities. 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
-----------------
Concurrent Docetaxel Plus Cisplatin or Cisplatin Alone With Intensity-modulated Radiotherapy in High Risk Locregionally Advanced Nasopharyngeal Carcinoma: a Phase 2 Randomized Controlled Trial

Conditions
-----------------
Nasopharyngeal Carcinoma

Intervention / Treatment
-----------------
* Drug: Cisplatin 2
* Drug: Docetaxel
* Drug: Cisplatin 1
* Radiation: Intensity-modulated radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma. Tumor staged as T1N3M0, T2-3N2-3M0 or T4N0-3M0 (the 2010 UICC/AJCC staging system). Pretreatment EBV DNA ≥ 1500 copies/mL. Karnofsky scale (KPS) ≥ 70. Adequate marrow: leucocyte count ≥ 4×10E9/L, hemoglobin ≥ 110g/L and platelet count ≥ 100×10E9/L. Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin ≤ 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN. Adequate renal function: creatinine clearance ≥ 60 ml/min or creatinine ≤ 1.5×ULN. Patients must give written informed consent. Exclusion Criteria: 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 radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume). Prior radiotherapy, 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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: TP plus IMRT<br>Concurrent chemotherapy: TP - Docetaxel 60mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy | Drug: Docetaxel<br>* Docetaxel 60 mg/m2, D1 every 3 weeks for 3 cycles<br>* Other names: T;Drug: Cisplatin 1<br>* Cisplatin 25 mg/m2, D1-3 every 3 weeks for 3 cycles<br>* Other names: P;Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<br>* Other names: IMRT;|
| Active Comparator: DDP plus IMRT<br>Concurrent chemotherapy: DDP - Cisplatin 100 mg/m2, D1 every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy | Drug: Cisplatin 2<br>* Cisplatin 100 mg/m2, D1 every 3 weeks for 3 cycles<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<br>* Other names: IMRT;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | two year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| failure-free survival |  | two year | 
| distant metastasis-free survival |  | two year | 
| locoregional relapse-free survival |  | two year | 
| Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0 |  | up to two months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NPC, concurrent chemotherapy, docetaxel, cisplatin