Induction Chemotherapy and Immunotherapy Combined Radiotherapy With or Without Concurrent Chemotherapy for Stage III-IVa NPC

Study Overview
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Brief Summary
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The purpose of this study is to compare induction chemotherapy (gemcitabine+cisplatin) plus immunotherapy with concurrent chemoradiotherapy (CCRT) or RT alone in patients with stage III-IVa nasopharyngeal carcinoma(NPC), in order to confirm the value of Immunotherapy and concurrent chemotherapy in NPC patients.

Detailed Description
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Patients Patients with stage III-Iva(except T3N0M0) non-keratinizing NPC (UICC/AJCC 8th edition) are randomly assigned to receive immunotherapy and induction chemotherapy plus CCRT or RT alone. Patients in both groups receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. The immunotherapy and induction chemotherapy plus CCRT group receive cisplatin 80-100 mg/m² every 3 weeks for 2 cycles, concurrently with intensity-modulated radiotherapy (IMRT). 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. Our primary endpoint is failure-free survival(FFS). 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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Prospective Randomized Trial Comparing Induction Chemotherapy and Immunotherapy Combined Radiotherapy With or Without Concurrent Chemotherapy for Stage III-IVa Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: without concurrent cisplatin chemotherapy
* Drug: with concurrent cisplatin chemotherapy


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(except T3N0M0) (according to the 8th AJCC 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 > 65 or < 18. Treatment with palliative intent. 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 RT (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: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The immunotherapy and induction chemotherapy plus RT alone group<br>Patients receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT) alone. | Drug: without concurrent cisplatin chemotherapy<br>* IMRT without concurrent cisplatin chemotherapy<br>|
| Active Comparator: The immunotherapy and induction chemotherapy plus CCRT group<br>Patients receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) , cisplatin (80mg/m² d1) every 3 weeks for three cycles and cisplatin 80-100 mg/m² every 3 weeks for 2 cycles, concurrently with intensity-modulated radiotherapy (IMRT) | Drug: with concurrent cisplatin chemotherapy<br>* IMRT with concurrent cisplatin chemotherapy<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 rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause | 3 years | 
| Locoregional failure-free survival | Locoregional failure-free survival is calculated from randomization to the first locoregional failure | 3 years | 
| Distant failure-free survival | Distant failure-free survival is calculated from randomization to the first remote failure | 3 years |