Effect of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy in High Risk Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The investigators aim to evaluate the survival benefit from triple combination of induction, concurrent and aduvant chemotherapy versus concurrent chemotherapy alone for high risk locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

Detailed Description
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All eligible patients receive intensity-modulated radiotherapy (IMRT) with a total dose of 68 to 70 Gy in 33 fractions to the primary tumor. Patients in the experimental arm receive triple therapy of induction, concurrent and adjuvant chemotherapy. Induction chemotherapy consists of docetaxel 75 mg/m², D1 and cisplatin 25 mg/m², D1-3 every 3 weeks for 2 cycles. Concurrent chemotherapy in the experimental arm consists of cisplatin 25 mg/m², D1-3 every 3 weeks and Xeloda 2000mg/m², D1-14 for 3 cycles. Adjuvant chemotherapy consists of Xeloda 2500mg/m², D1-14 for 2 cycles. Concurrent chemotherapy in the control arm consists of cisplatin 100 mg/m², D1 every 3 weeks for 3 cycles.The primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), 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
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Randomized Phase 3 Trial of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy Versus Concurrent Chemotherapy Alone in High Risk Nasopharyngeal Carcinoma Patients Treated With Intensity-modulated Radiotherapy

Conditions
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Nasopharyngeal Carcinoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma. Tumor staged as T4N0-3M0 or T1-3N3M0 (the 2010 UICC/AJCC staging system). Pretreatment EBV DNA ≥ 4000 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. Dihydropyrimidine dehydrogenase deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: IC plus CC plus IMRT plus AC<br>Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles | Drug: Cisplatin 1<br>* Cisplatin 25 mg/m2, D1-3<br>* Other names: DDP;Drug: Docetaxel<br>* Docetaxel 60mg/m2, D1<br>* Other names: T;Drug: Xeloda<br>* Xeloda 2000mg/m2, D1-14 in concurrent chemotherapy and Xeloda 2500mg/m2, D1-14 in adjuvant chemotherapy<br>* Other names: X;Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<br>* Other names: IMRT;|
| Active Comparator: CC plus IMRT<br>Concurrent chemotherapy: Cisplatin 100 mg/m2, D1, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy | Drug: Cisplatin 2<br>* Cisplatin 100 mg/m2, D1<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* Intensity-modulated radiotherapy<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 |  | Two year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall 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 |  | two months |