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

Phase 3

Not yet recruiting

Interventions: Drug: without concurrent cisplatin chemotherapy
Drug: with concurrent cisplatin chemotherapy

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
The immunotherapy and induction chemotherapy plus RT alone group	without concurrent cisplatin chemotherapy	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.
The immunotherapy and induction chemotherapy plus CCRT group	with concurrent cisplatin chemotherapy	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)

Primary Outcome Measures

Name	Time	Method
Failure-free survival	3 years	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

Secondary Outcome Measures

Name	Time	Method
Distant failure-free survival	3 years	Distant failure-free survival is calculated from randomization to the first remote failure
Overall survival	3 years	Overall survival is calculated from randomization to death from any cause
Locoregional failure-free survival	3 years	Locoregional failure-free survival is calculated from randomization to the first locoregional failure

Locations (1): Department of radiation oncology, Fujian cancer hospital
🇨🇳
Fuzhou, Fujian, China