PD-1 Combined With Intensity Modulated Radiation Therapy in the Treatment of Intermediate-risk Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of PD-1 immune checkpoint inhibitor combined with intensity modulated radiation therapy in the treatment of intermediate-risk nasopharyngeal carcinoma (T2-3N0 or T1-2N1 stage and EBV-DNA≤4000 copy/ml).

Detailed Description
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To evaluate the safety and efficacy of PD-1 immune checkpoint inhibitor combined with intensity modulated radiation therapy in the treatment of intermediate-risk nasopharyngeal carcinoma (T2-3N0 or T1-2N1 stage and EBV-DNA≤4000 copy/ml).The primary end point is safety, the secondary end points are short-term efficacy,overall survival (OS), progression-free survival (PFS),Distant metastasis-free survival(DMFS),adverse effects ,quality of life and immune status assessment.

Official Title
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PD-1 Immune Checkpoint Inhibitor Combined With Intensity Modulated Radiation Therapy in the Treatment of Intermediate-risk Nasopharyngeal Carcinoma (T2-3N0 or T1-2N1 and EBV-DNA≤4000 Copy/ml),A Single-arm, Phase II Clinical Trial

Conditions
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Nasopharyngeal Carcinoma, T2-3N0 or T1-2N1, EBV-DNA≤4000 Copy/ml

Intervention / Treatment
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* Drug: Toripalimab
* Procedure: Intensity modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed patients who have not received radiotherapy or chemotherapy Pathologically diagnosed as non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated, WHO classification type II or type III). T2-3N0 or T1-2N1 stage and EBV-DNA≤4000 copy/ml (AJCC 8th version) and EBV-DNA≤4000copies/ml Male or non-pregnant female Age between 18 and 65 Eastern Cooperative Oncology Group（ECOG）score of 0-1. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109/L, platelet (PLT) ≥100×109/L. Liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <2.0 times the upper limit of normal (ULN); total bilirubin <2.0×ULN. Renal function: creatinine clearance rate ≥60ml/min or serum creatinine <1.5×ULN. The patient has signed the informed consent Exclusion Criteria: The pathology is keratinizing squamous cell carcinoma (WHO classification is type I). Patients with recurrence and distant metastasis. Patients who have undergone radiotherapy or chemotherapy. Active hepatitis B (HBV-DNA≥500). Patients with autoimmune diseases. Patients with HIV infection. At the same time suffering from other uncontrolled serious diseases. Persons with abnormal functions of the heart, brain, lungs and other important organs. Age> 65 years. pregnancy or breast feeding. Persons with personality or mental illness, without or with limited capacity for civil conduct

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-1 Immune Checkpoint Inhibitor Combined With Intensity Modulated Radiation Therapy<br>Intensity modulated radiation therapy combined with toripalimab in the treatment of nasopharyngeal carcinoma，once every 2 weeks, 10 cycles in total | Drug: Toripalimab<br>* PD-1 Immune Checkpoint Inhibitor Combined With IMRT,used at 2 weeks before radiotherapy, once every 2 weeks, 10 cycles in total<br>* Other names: Programmed cell death protein 1(PD-1)；Immune checkpoint inhibitors（ICIs);Procedure: Intensity modulated radiotherapy<br>* Intensity modulated radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | The severity of adverse events will be determined by the investigator based on CTCAE v 5.0 | Recent evaluation: 3 months after the end of treatment；Long-term follow-up: 1 5 years after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | Patients in clinical trials were randomized to the time of death from any cause | 2 years | 
| progression-free survival (PFS) | The time from the commencement of a randomized clinical trial to the progression of tumorigenesis (in any respect) or death from any cause | 2 years | 
| Distant metastasis-free survival(DMFS) | Patients in clinical trials were randomized to the time of distant metastasis | 2 years | 
| Response rate (based on RECIST ver1.1) | According to the remission assessment criteria of solid tumors，divided into CR, PR, SD, PD. CR(complete response) All target lesions disappeared and no new lesions appeared PR ( partial response) reduction of the sum of the largest diameters of target lesions by ≥30%) SD(stable disease)the sum of the largest diameters of target lesions does not shrink to PR, or increases to PD PD(progressive disease) The sum of the largest diameters of target lesions increases by at least 20%, or new lesions appear | Recent evaluation: 3 months after the end of treatment；Long-term follow-up: 1 5 years after the end of treatment |