Induction Chemotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to compare induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of induction chemotherapy in NPC patients.

Detailed Description
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Patients presented with non-keratinizing NPC and stage T3-4N1M0/TxN2-3M0 are randomly assigned to receive induction chemotherapy (docetaxel+cisplatin+fluorouracil) plus concurrent chemoradiotherapy (investigational arm) or concurrent chemoradiotherapy (control arm). Patients in both arms receive radical radiotherapy, and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. Patients in the investigational arm receive docetaxel(60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy. Patients are stratified according to the treatment centers and stage. The primary end point is failure-free survival (FFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), initial response rates after treatments and toxic effects. All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.

Official Title
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Prospective Randomized Trial Comparing Induction Chemotherapy Plus Concurrent Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Docetaxel, cisplatin and fluorouracil
* Radiation: Concurrent chemoradiotherapy


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) histologically type). Tumor staged as T3-4N1/N2-3 (according to the 7th American Joint Commission on Cancer edition). No evidence of distant metastasis (M0). Satisfactory performance status: Karnofsky scale (KPS) > 70. Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L and platelet count ≥100000/μL. 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: creatinine clearance ≥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 or basaloid squamous cell carcinoma. Age ≥60 years or <18 years. Treatment with palliative intent. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. Pregnancy or lactation. History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume). Prior 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
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Minimum Age: 18 Years
Maximum Age: 59 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: Induction chemotherapy and concurrent chemoradiotherapy<br>Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy, and then receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. | Drug: Docetaxel, cisplatin and fluorouracil<br>* Patients receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.<br>* Other names: TPF induction chemotherapy;Radiation: Concurrent chemoradiotherapy<br>* Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.<br>* Other names: Radical radiotherapy and concurrent cisplatin;|
| Active Comparator: Concurrent chemoradiotherapy<br>Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy. | Radiation: Concurrent chemoradiotherapy<br>* Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.<br>* Other names: Radical radiotherapy and concurrent cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival | Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first. | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 3-year | 
| Locoregional failure-free survival | The latency (ie, time from randomisation) to the first locoregional failure | 3-year | 
| Distant failure-free survival | The latency (ie, time from randomisation) to the first remote failure | 3-year | 
| The initial response rates after treatments |  | A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy | 
| Toxic effects |  | During and after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, Induction chemotherapy, Clinical trial