PD-1 Antibody Versus Best Supportive Care After Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This trial is aimed to investigate whether adjuvant PD-1 antibody treatment could improve survival in locoregionally advanced nasopharyngeal carcinoma compared to best supportive care.

Detailed Description
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In this multicenter, randomised controlled, phase 3 trial, patients with stage III-IVA (AJCC/UICC 8th system, except T3-4N0 and T3N1) non-metastatic nasopharyngeal carcinoma will be randomized in a 1:1 ratio to recieve PD-1 antibody for 12 doses every 3 weeks or best supportive care after curative chemoradiation.

Official Title
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Camrelizumab (PD-1 Antibody) Compared With Best Supportive Care After Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: a Multi-center, Randomised Controlled, Phase 3 Trial (PACIFIC-NPC)

Conditions
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Nasopharyngeal Neoplasms

Intervention / Treatment
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* Drug: Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed nasopharyngeal carcinoma. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0). Completed protocol-specified curative chemoradiotherapy, including gemcitabine and cisplatin induction chemotherapy, intensity-modulated radiotherapy, and concurrent cisplatin chemotherapy. Completion of the last radiation dose within 1 to 14 days before randomization 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: Age > 65 or < 18. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml Hepatitis C virus (HCV) antibody positive Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia). 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. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed. Has a known history of interstitial lung disease. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future. Is pregnant or breastfeeding. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma. Has known allergy to large molecule protein products or any compound of camrelizumab. Has a known history of human immunodeficiency virus (HIV) infection. 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 patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant PD-1 antibody arm<br>Patients randomized to this arm will receive PD-1 antibody (SHR-1210), 200mg, ivdrip (>30 minutes), d1, q3w × 12 cycles, begining at 4-6 weeks after chemoradiation | Drug: Camrelizumab<br>* Camrelizumab is an antibody targeting PD-1 developed by Jiangsu Hengrui Medicine, China.<br>* Other names: SHR-1210;|
| No Intervention: Best supportive care<br>Patients randomized to this arm will receive best supportive care after chemoradiation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| failure-free survival | calculated from the date of randomisation to the date of locoregional failure, distant failure, or death from any cause, whichever occurred first. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | calculated from date of randomisation to death | 5 years | 
| distant metastasis-free survival | calculated from date of randomisation to the first distant failure | 3 years | 
| locoregional recurrence-free survival | calculated from date of randomisation to the first locoregional failure | 3 years | 
| adverse events (AEs) and severe adverse events (SAE) | graded according to NCI CTCAE v5.0 | 3 years | 
| quality of life (QoL) | the change of QoL from randomization to 36 months after chemoradiation, graded according to EORTC QLQ-C30 V3.0 | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1 antibody, Adjuvant treatment, Immune checkpoint inhibitors