Sintilimab in Combination With Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The program aims to enroll patients with stage high risk (AJCC 8th, T3-4N2-3M0) . Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Sintilimab, and then receive 11 cycles of Sintilimab after intensity-modulated radiotherapy (IMRT). All patients will receive IMRT. Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 17 cycles.

Detailed Description
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The program aims to enroll patients with stage high risk (AJCC 8th, T3-4N2-3M0) locoregionally advanced nasopharyngeal carcinoma (LANPC). Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Sintilimab (200mg q3wk), and then receive 11 cycles of Sintilimab after intensity-modulated radiotherapy (IMRT). All patients will receive IMRT. IMRT：PGTVnx: 69.96 Gy /33f, PGTVnd: 66 70 Gy /33f, PCTVnd: 63 64 Gy/33f, PCTV1: 60 62 Gy/33f, PCTV2: 54 56 Gy/33f. Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 17 cycles.

Official Title
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Sintilimab (PD-1 Antibody) in Combination With Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma: a Single-arm, Multicentre, Phase 2 Trial

Conditions
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Nasopharyngeal Carcinoma, Sintilimab

Intervention / Treatment
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* Drug: Sintilimab (PD-1 Antibody)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed Non-keratinizing nasopharyngeal carcinoma. Tumor staged as III-IVA (AJCC 8th, T3-4N2-3M0). Eastern Cooperative Oncology Group performance status ≤1. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula). Patients must be informed of the investigational nature of this study and give written informed consent. Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug. Exclusion Criteria: 1.Age > 70 or < 18. 2.Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml 3.Hepatitis C virus (HCV) antibody positive 4.Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment. 5.Has a known history of interstitial lung disease. 6.Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed. 7.Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future. 8.Is pregnant or breastfeeding. 9.Has a history of other malignancies except carcinoma in situ, adequately treated non-melanoma skin cancer, and papillary thyroid cancer. 10.Has known allergy to large molecule protein products or any compound of sintilimab. 11.Has a known history of human immunodeficiency virus (HIV) infection. 12.Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sintilimab+Chemoradiotherapy<br>Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Sintilimab, and then receive 11 cycles of Sintilimab after intensity-modulated radiotherapy (IMRT). All patients will receive IMRT. Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 17 cycles. | Drug: Sintilimab (PD-1 Antibody)<br>* Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Sintilimab, and then receive 11 cycles of Sintilimab after intensity-modulated radiotherapy (IMRT). All patients will receive IMRT. Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 17 cycles.<br>* Other names: PD-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival (PFS) | Defined from date of recruit to date of first documentation of progression or death due to any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined from date of recruit to date of first documentation of death from any cause or censored at the date of the last follow-up. | 5 years | 
| Locoregional Relapse-Free Survival (LRRFS) | Defined from date of recruit to date of first documentation of locoregional relapse or until the date of the last follow-up visit. | 5 years | 
| Distant Metastasis-Free Survival (DMFS) | Defined from date of recruit to date of first documentation of distant metastases or until the date of the last followup visit. | 5 years | 
| Objective Response Rate （ORR） | An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). | through study completion, an average of 1 year | 
| Incidence rate of adverse events (AEs) | Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0 | 5 years | 
| Serious adverse events (SAE) | Serious adverse events (SAE) is defined as either death, life-threatening, or Permanent or severe disability/incapacity. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal Carcinoma, Sintilimab, high risk