Induction Chemotherapy Plus Radiotherapy Alone 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 (TPF or GP) plus radiotherapy alone with induction chemotherapy plus concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

Official Title
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Induction Chemotherapy Plus Radiotherapy Alone Versus Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: gemcitabine and cisplatin; docetaxel, cisplatin and fluorouracil
* Radiation: IMRT
* Radiation: IMRT and concurrent cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly pathologically confirmed as non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated, ie WHO type II or III). Age ≥ 18 and ≤ 65 years old. Tumor staged as III/IVa (according to the 8th AJCC edition). No evidence of distant metastasis (M0). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Adequate marrow: White blood cells (WBC) ≥ 4 × 10^9/L, hemoglobin (HGB) ≥ 90 g/L, platelets (PLT) ≥ 100 × 10^9/L (or within the normal range of the laboratory) 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. Written informed consent. Exclusion Criteria: WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma. Age > 65 or < 18. Treatment with palliative intent. Previous history of malignant tumors, well-treated basal cell carcinoma or squamous cell carcinoma and cervical carcinoma in situ outer. Pregnancy or lactation. History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume), chemotherapy or surgery (except diagnostic) to primary tumor or nodes. Any other serious diseases, which may bring greater risk or affect the compliance of the test, 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: 65 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 RT<br>Patients receive GP(gemcitabine+cisplatin) or TPF(docetaxel+cisplatin+fluorouracil) every three weeks for three cycles before the radiotherapy, and then receive radical radiotherapy and cisplatin (100mg/m^2) every three weeks for three cycles during radiotherapy. | Drug: gemcitabine and cisplatin; docetaxel, cisplatin and fluorouracil<br>* Patients receive GP gemcitabine (1000 mg/m^2 d1,8) and cisplatin (80mg/m^2 d1) or TPF docetaxel (60mg/m^2 on day 1), cisplatin (60mg/m^2 on day 1) and fluorouracil (600mg/m^2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.<br>* Other names: GP;TPF;Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor.<br>|
| Active Comparator: IC plus CCRT<br>Patients receive GP(gemcitabine+cisplatin) or TPF(docetaxel+cisplatin+fluorouracil) every three weeks for three cycles before the radiotherapy, and then receive radical radiotherapy. | Drug: gemcitabine and cisplatin; docetaxel, cisplatin and fluorouracil<br>* Patients receive GP gemcitabine (1000 mg/m^2 d1,8) and cisplatin (80mg/m^2 d1) or TPF docetaxel (60mg/m^2 on day 1), cisplatin (60mg/m^2 on day 1) and fluorouracil (600mg/m^2 on Days 1 to 5) every three weeks for three cycles before the radiotherapy.<br>* Other names: GP;TPF;Radiation: IMRT and concurrent cisplatin<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor, concurrently with cisplatin 100 mg/m^2 every 3 weeks for 3 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Disease-free survival rate is calculated from the date of randomization 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 recurrence-free survival | Locoregional recurrence-free survival is calculated from randomization to the first locoregional recurrence. | 3-year | 
| Distant metastasis-free survival | Distant metastasis-free survival is calculated from randomization to the first remote metastases. | 3-year | 
| Objective response rates after treatments |  | At the end of Cycle 3 of induction chemotherapy (each cycle is 21 days) and 16 weeks after completion of radiotherapy | 
| Number of participants with adverse events | Incidence of acute toxicity | Every week during treatment, up to 4 weeks after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, Induction Chemotherapy, Concurrent Chemoradiotherapy