Toripalimab for Local-regional Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a phase 3, multicentre, randomised controlled trial to study the effectiveness and toxicity of PD-1 antibody Toripalimab combined with concurrent cisplatin chemoradiotherapy versus cisplatin concurrent chemoradiotherapy alone in treating patients with locoregionally recurrent nasopharyngeal carcinoma.

Detailed Description
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Nasopharyngeal carcinoma (NPC) is endemic in southern China, southeast Asia, and northern Africa. According to a survey from the International Agency for Research on Cancer, there were an estimated 129,079 new cases and 72,987 related deaths in 2018. Radiotherapy is the primary treatment option. Due to advances in disease management, diagnostic imaging, radiotherapy technology, and the broader application of systemic therapy, the prognosis of NPC has improved signifificantly.Nevertheless, localregional recurrence will occur in about 10% patients. Because of radiation resistance, the prognosis of re-irradiation is poor for recurrent nasopharyngeal carcinoma. Hence, there is an urgent need for novel therapies to improve survival and reduce treatment-related toxicity in recurrent NPC patients. Emerging evidence shows that PD-1 antibody is effective for treating recurrent/metastastic NPC patients. This is a phase 3, multicentre, randomised controlled trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in treating patients with locoregionally recurrent nasopharyngeal carcinoma.

Official Title
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Toripalimab in Combination With Concurrent Chemoradiotherapy for Local-regional Recurrent Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial

Conditions
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Recurrent Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed recurrent nasopharyngeal carcinoma, or Two or more image examinations (MRI, and PET-CT) show the recurrent tumor staged as rT3-4N0-1M0或rT1-4N2-3M0 （according to the 8th AJCC edition） Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1 Neutrophil ≥ 1.5×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 1.5×ULN) With normal renal function test ( creatinine clearance ≥60 ml/min) sign an informed consent form Male and no pregnant female Exclusion Criteria: Age older than 65, or younger than 18 years old Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥200IU/ml, or 1000cps/ml. Patients with positive HCV antibody. Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, and skin disease (leukoderma, psoriasis, alopecia et al) who don't need systemic therapy can recruit. History of interstitial lung disease Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent. Receive or will receive live vaccine within 30 days prior to signing the informed consent. Women of child-bearing potential who are pregnant or breastfeeding. Suffered from malignant tumors, except the carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years. Hypersensitivity to macromolecular protein, or to any component of triplezumab. HIV positive. Severe, uncontrolled medical conditions and infections. Other diseases which may influence the safety or compliance of the clinical trial, such as heart failure with symptom, unstable angina, myocardial infarction, active infections those need systemic therapy, mental illness, or their family and society factors.

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: Toripalimab+CCRT<br>Toripalimab 240mg, and Cisplatin 100mg/m2 (every three weeks),D1,D22,D43 of intensity modulated radiotherapy (IMRT), followed by Toripalimab 240mg every 3 weeks with a total of 9 cycles as adjuvant anti-PD-1 immunotherapy. IMRT: total dose 60-66Gy, 1.8-2.0Gy/f | Drug: Toripalimab<br>* anti-PD-1 antibody<br>* Other names: JS001;|
| No Intervention: CCRT alone<br>Cisplatin 100mg/m2(every three weeks),D1,D22,D43 of intensity modulated radiotherapy (IMRT). IMRT: total dose 60-66Gy, 1.8-2.0Gy/f | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined from date of randomization to date of first documentation of death from Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival (PFS) | Defined from date of randomization to date of first documentation of progression or death due to any cause. | 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) . | 3 months | 
| 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 | 
| Change of QoL (quality of life) | QoL scores were assessed by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before radiotherapy, at the end of radiotherapy, at 12 months after radiotherapy. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Nasopharyngeal Carcinoma, Toripalimab, Concurrent chemoradiotherapy