Tirelizumab Plus Surgery vs Surgery Alone for Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Through open-label, single-center, randomised clinical trials, we intend to demonstrate that PD-1 treatment added to salvage surgery could further decrease the rate of disease progression and improve the survival outcome of patients with locally recurrent nasopharyngeal carcinoma compared with those treated with salvage surgery alone.

Official Title
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Tirelizumab Plus Surgery vs Surgery Alone for Recurrent Nasopharyngeal Carcinoma：a Prospecitve, Parallel, Phase II, Randomized Clinical Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Tirelizumab
* Procedure: salvage surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed recurrent nasopharyngeal carcinoma The recurrence time is more than 6 months from the end of radiotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. According to the TNM staging criteria of nasopharyngeal carcinoma (AJCC, 8th Edition, 2017), rT1, rT2, rT3, and rT4 patients who can be completely resected by surgery as assessed by the surgical team. Resectable recurrent regional lymph node diseases (recurrent N1-3) without prevertebral fascia, cervical vertebrae, or common/internal carotid artery involvement. Given written informed consent. Exclusion Criteria: Has severe medical disorder, important organ dysfunction, and/or a substantial history of mental illness. Has known subjects with other malignant tumors. Has participated in other drug trials within 3 months of planned start of study treatment. Received a systematic or local glucocorticoid therapy within 4 weeks of planned start of study treatment. Suffered from diseases need long-term treatment with immunosuppressive drugs, or required systematic or local glucocorticoid therapy with immunosuppressive doses. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) agent. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive. Has received a live vaccine within 4 weeks of planned start of study treatment. Pregnancy or breast feeding. Cannot complete regular follow-up. Local recurrence of nasopharyngeal carcinoma with distant metastasis

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirelizumab plus salvage surgery<br>Tirelizumab: Tirelizumab treatment after salvage surgery. Salvage surgery: endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma | Drug: Tirelizumab<br>* Tirelizumab: 200 mg, intravenous injection over 60 minutes (Q3W); Tirelizumab should be applied since 2-6 weeks after surgery until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, investigator decision, or 1 year.<br>* Other names: PD-1 antibody;Procedure: salvage surgery<br>* Endoscopic nasopharyngectomy for recurrent nasopharyngeal tumor<br>|
| Active Comparator: salvage surgery alone<br>Salvage surgery: endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma | Procedure: salvage surgery<br>* Endoscopic nasopharyngectomy for recurrent nasopharyngeal tumor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival(PFS) | Defined as the time interval from randomization to the observation of disease progression or the occurrence of death from any cause | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | Defined as the time interval from randomization to death due to any cause. | 2 years | 
| Locoregional failure-free survival(LRRFS) | The LRRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit | 2 years | 
| Distant metastasis-free survival(DMFS) | The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit. | 2 years | 
| Incidence of treatment related complications | Incidence of treatment related complications of tirelizumab or surgical treatment during follow-up | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Nasopharyngeal Carcinoma, Tirelizumab, Immunotherapy, Endoscopic surgery, Survival