Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of sequential chemoradiotherapy (induction chemotherapy + intensity-modulated radiotherapy +adjuvant chemotherapy) with induction chemotherapy plus concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of sequential chemoradiotherapy in NPC patients.

Detailed Description
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Patients with non-keratinizing NPC III-IVA (UICC/AJCC 8th edition) are randomly assigned to receive sequential chemoradiotherapy (induction chemotherapy + intensity-modulated radiotherapy + adjuvant chemotherapy) or induction chemotherapy plus concurrent chemoradiotherapy. Intensity-modulated radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4 Gy to the primary tumor. The induction or adjuvant chemotherapy is given gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for two cycles. The concurrent chemotherapy is given cisplatin 30 mg/m² every week concurrently with IMRT. Our primary endpoint is failure-free survival(FFS) and grade III mucositis during radiation. Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. 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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Non-inferiority Prospective Randomized Trial Comparing Sequential 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: gemcitabine and cisplatin (Induction and adjuvant chemotherapy)
* Radiation: IMRT
* Drug: gemcitabine and cisplatin (Induction chemotherapy)
* Radiation: IMRT and concurrent cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type) Tumor staged as III-IVA (according to the 8th AJCC edition). Satisfactory performance status: Karnofsky scale (KPS) ≥ 70. Age between 18 and 65 years old. Adequate marrow: Neutrophil count ≥2000/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 ≤ 1.5ULN. 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: Evidence of distant metastasis Prior chemotherapy, radiotherapy or surgery (except diagnostic) to primary tumor or nodes. Other previous or concomitant cancer. Pregnancy or lactation. Presence of an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, immune deficiency, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or 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
Interventional Model Description: Stratified by stage
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction chemotherapy+IMRT+adjuvant chemotherapy<br>Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), followed by gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles. | Drug: gemcitabine and cisplatin (Induction and adjuvant chemotherapy)<br>* Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before IMRT and after IMRT.<br>Radiation: IMRT<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4 Gy to the primary tumor<br>|
| Active Comparator: Induction chemotherapy+IMRT and concurrent cisplatin<br>Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 30 mg/m² every week. | Drug: gemcitabine and cisplatin (Induction chemotherapy)<br>* Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before concurrent chemoradiotherapy.<br>Radiation: IMRT and concurrent cisplatin<br>* Intensity modulated-radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4Gy to the primary tumor, concurrently with cisplatin 30mg/m² every week.<br>|

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 | 
| Grade III or more mucositis | Grade III or more mucositis during radiotherapy | From the start of radiotherapy to 30 days after radiotherapy | 

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 | Locoregional failure-free survival is calculated from randomization to the first locoregional failure. | 3-year | 
| Distant failure-free survival | Distant failure-free survival is calculated from randomization to the first remote failure. | 3-year | 
| Short-term treatment response | Treatment response after induction chemotherapy, IMRT and completion of treatment. | Two weeks after completion of induction chemotherapy. Three months after completion of the radiotherapy. | 
| Number of participants with adverse events | Incidence of acute and late toxicity | up to 3 years | 
| Quality of Life | Use EORTC QLQ-HN35. | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, concurrent chemoradiotherapy, sequential chemoradiotherapy