Adding PD-1 Inhibitor to Neoadjuvant and Adjuvant for NPC

Study Overview
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Brief Summary
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This is a randomized clinical trial comparing neoadjuvant and adjuvant PD-1 inhibitor Toripalimab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy versus neoadjuvant chemotherapy and concurrent chemoradiotherapy alone in high-risk nasopharyngeal carcinoma

Official Title
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Adding Neoadjuvant and Adjuvant PD-1 Inhibitor to Neoadjuvant Chemotherapy Plus Concurrent Chemoradiotherapy in the Treatment of High-risk Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: PD-1 antibody
* Drug: Gemcitabine
* Drug: Cisplatin
* Radiation: IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma Clinical staged as T4 or N3 （according to the 8th AJCC edition） No evidence of distant metastasis (M0) Male and no pregnant female ECOG (Eastern Cooperative OncologyGroup) scale 0-1 WBC ≥ 4×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L Normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 2.0×ULN) Normal renal function test ( creatinine clearance ≥60 ml/min) Exclusion Criteria: Recurrent or distant metastatic disease. History of malignant tumors (except cured basal cell carcinoma or uterine cervical carcinoma in situ) within the last 5 years. History of radiotherapy or chemotherapy. History of immunodeficiency disease History of organ transplantation Presence of life-threatening illness Uncontrolled hypercalcemia Severe uncontrolled medical conditions or active infectious diseases Use of large doses of glucocorticoids, anti-cancer monoclonal antibodies, or other immunosuppressive agents within 4 weeks. Pregnant or breastfeeding female Emotional disturbance or mental illness Refusal or inability to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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: Arm A<br>IC with anti-PD1 mab+CCRT+anti-PD1 mab | Drug: PD-1 antibody<br>* neoadjuvant: PD-1 inhibitor Toripalimab 240mg combined with neoadjuvant chemotherapy by cis Platinum and gemcitabine every 3 weeks for 3 cycles ; adjuvant: Toripalimab 240mg every 3 weeks for 9 cycles after concurrent chemoradiotherapy<br>Drug: Gemcitabine<br>* neoadjuvant chemotherapy: 1000mg/m2 in day 1 and day 8 and repeats every 3 weeks for 3 cycles<br>Drug: Cisplatin<br>* neoadjuvant chemotherapy: 80mg/m2 in day 1, and repeats every 3 weeks for 3 cycles. Concurrent chemoradiotherapy: Cisplatin 100mg/m2 in day 1, 22, and 43 during IMRT<br>Radiation: IMRT<br>* 70Gy to GTV, 60Gy to CTV1 and 54Gy to CTV2 in 32 to 33 fractions<br>|
| Active Comparator: Arm B<br>IC+CCRT | Drug: Gemcitabine<br>* neoadjuvant chemotherapy: 1000mg/m2 in day 1 and day 8 and repeats every 3 weeks for 3 cycles<br>Drug: Cisplatin<br>* neoadjuvant chemotherapy: 80mg/m2 in day 1, and repeats every 3 weeks for 3 cycles. Concurrent chemoradiotherapy: Cisplatin 100mg/m2 in day 1, 22, and 43 during IMRT<br>Radiation: IMRT<br>* 70Gy to GTV, 60Gy to CTV1 and 54Gy to CTV2 in 32 to 33 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival (PFS) | From date of randomization to date of first documentation of progression or death due to any cause. | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | From date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up. | 3 year | 
| Distant Metastasis-Free Survival (DMFS) | From date of randomization to date of first documentation of distant metastases or until the date of the last followup visit. | 3 year | 
| Locoregional Relapse-Free Survival (LRRFS) | From date of randomization to date of first documentation of locoregional relapse or until the date of the last follow-up visit. | 3 year | 
| Objective Response Rate （ORR） | 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). | within 3 weeks after neoadjuvant treatment and 3 months after concurrent chemoradiotherapy | 
| adverse events (AEs) | Treatment-related AEs (trAEs) and immune-related AEs (irAEs) according to the Common Terminology Criteria for Adverse Events, version 5.0 | 3 year |