Phase III Study of Camrelizumab in Combination With Chemotherapy in Recurrent/Metastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This study is a randomized, placebo-controlled, double-blind, multicenter phase III clinical study. Target population is patients with recurrent/metastatic nasopharyngeal carcinoma who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of camrelizumab in combination with gemcitabine and cisplatin with placebo in combination with gemcitabine and cisplatin in study population in China. camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Detailed Description
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In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Treatment cycles of chemotherapy will be at most 6 weeks which will be decided by investigators. Progression-free survival (PFS) determined by the Independent Review Committee (IRC) will be the primary outcome measures.

Official Title
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A Phase III, Randomized, Double-Blind, Multi-center Study to Investigate the Efficacy and Safety of Camrelizumab+Gemcitabine+Cisplatin Versus Placebo+Gemcitabine+Cisplatin in Subjects With Recurrent/Metastatic Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: Placebos
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years and ≤75 years; Subjects with histopathological diagnosis of nasopharyngeal carcinoma; Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment; Has not received prior systemic treatment; Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Subject must have a measurable target lesion based on RECIST v1.1; Exclusion Criteria: Allergic to monoclonal antibodies, any camrelizumab components, gemcitabine, cisplatin and other platinum drugs; Prior therapy as follow: Anti-PD-1 or anti-PD-L1; Received last dose of anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within 4 weeks of the first dose of study medication; Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone or equivalent for replacement therapy; Received major operations or serious injuries within 4 weeks of the first dose of study medication; Not recovered to ≤CTCAE 1 from adverse events (except for hair loss) due to a previously anti-tumor treatment; Pregnancy or breast feeding;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab + Gemcitabine + Cisplatin<br>subject will receive camrelizumab 200mg every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles | Drug: Camrelizumab<br>* Maximum 6 cycles for combined therapy. Camrelizumab maintenance.<br>* Other names: SHR-1210;Drug: Gemcitabine<br>* Maximum 6 cycles for combined therapy.<br>* Other names: Gemcitabine Hydrochloride for Injection;Drug: Cisplatin<br>* Maximum 6 cycles for combined therapy.<br>* Other names: Cisplantin Injection;|
| Active Comparator: Placebos + Gemcitabine + Cisplatin<br>subject will receive placebos every 3 weeks, cisplatin 80mg/m2 on Day 1 of each 21 day, at most 6 cycles, gemcitabine 1000mg/m2, Day 1 and Day 8 of each 21 day, maximum 6 cycles | Drug: Placebos<br>* Maximum 6 cycles for combined therapy.<br>* Other names: Placebo - Concentrate;Drug: Gemcitabine<br>* Maximum 6 cycles for combined therapy.<br>* Other names: Gemcitabine Hydrochloride for Injection;Drug: Cisplatin<br>* Maximum 6 cycles for combined therapy.<br>* Other names: Cisplantin Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee according to RECIST v1.1 or death from any cause, whichever occurs first. | up to 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival (PFS) assessed by investigators according to RECIST V 1.1 | up to 24 month | 
| Objective Response Rate (ORR) | The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1 | up to 24 month | 
| Disease Control Rate (DCR) Disease Control Rate (DCR) | The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1 | up to 24 month | 
| Duration of Response (DoR) | According to Recist v 1.1 accessed by investigators | up to 24 month | 
| 2 years Overall Survival (OS) rate | The percentage of patients overall survival in 2 years | up to 24 month | 
| Adverse Events (AEs) | All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 4.03 | up to 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gemcitabine, Nasopharyngeal Carcinoma, Cisplatin, PD-1 Antibody