Chemoradiotherapy Plus Anti-PD1 in Recurrent NPC: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Study Overview
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Brief Summary
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This is a multicenter, open-label, randomized, controlled, phase III trial. The purpose of this trial is to evaluate the efficacy and toxicity of anti-PD-1 antibody combined with chemoradiotherapy versus chemoradiotherapy alone in recurrent nasopharyngeal carcinoma patients.

Official Title
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Chemoradiotherapy Combined With Programmed Death 1 Antibody in Recurrent Nasopharyngeal Carcinoma: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Chemotherapy
* Radiation: Intensity modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as local with or without regional recurrence after ≥1 year of radical treatment; Not suitable for surgery; Histologic diagnosis of NPC (WHO II/III); TNM stage rII-IVa (AJCC/UICC 8th); ECOG 0-1 point; No treatment to rNPC prior, such as radiotherapy, chemotherapy, immunotherapy or biotherapy; No contraindications to immunotherapy or chemoradiotherapy; Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L; Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN; Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula); Take effective contraceptions during and two months after treatment; Patients must be informed of the investigational nature of this study and give written informed consent. Exclusion Criteria: Treated with anti-tumor Chinese medicine treatment; Have recurrence with local necrosis; Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa; Unexplained fever > 38.5, except for tumor fever; Treated with ≥ 5 days antibiotics one month before enrollment; Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy); Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive; Have previously treated with PD-1 antibody or other immunotherapy for PD-1/PD-L1 pathway; Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment; Have known allergy to large molecule protein products or any compound of study therapy; Pregnant or breastfeeding; Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma; Have received a live vaccine within 30 days of planned start of study therapy Has psychiatric drug or substance abuse disorders that would interfere with cooperation with the requirements of the trial; Any other condition, including 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: 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: Chemoradiotherapy+anti-PD-1<br>Patients in this arm will receive three cycles of GP chemotherapy plus PD-1 antibody, then receive IMRT and PD-1 antibody maintenance for eight cycles. | Drug: Toripalimab<br>* 240mg, D1, every 3 weeks per cycle, three cycles with chemotherapy and eight cycles after IMRT<br>* Other names: JS001;Drug: Chemotherapy<br>* Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles<br>* Other names: GP;Radiation: Intensity modulated radiotherapy<br>* total 60-66Gy, 1.8-2.0Gy/f/day<br>* Other names: IMRT;|
| Active Comparator: Chemoradiotherapy<br>Patients in this arm will receive three cycles of GP chemotherapy, then receive IMRT. | Drug: Chemotherapy<br>* Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles<br>* Other names: GP;Radiation: Intensity modulated radiotherapy<br>* total 60-66Gy, 1.8-2.0Gy/f/day<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined as the time from date of recruitment to death from any cause. | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival | Defined as the time from date of recruitment to documented relapse or death from any cause. | three years | 
| Objective response rate through study completion, an average of nine months | The rate of patients get CR or PR after treatment | through study completion, an average of nine months | 
| Disease control rate through study completion, an average of nine months | The rate of patients get CR or PR or SD after treatment | through study completion, an average of nine months | 
| Incidence of nasopharyngeal necrosis and hemorrhage up to 3 years | Incidence of nasopharyngeal necrosis and hemorrhage after receiving treatment | up to three-year follow-up | 
| Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0) | Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0) for chemotherapy and immunotherapy-specific toxicities, and the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria for radiotherapy-specific toxicities. | through study completion, an average of nine months | 
| Late toxicity | Late toxicities were assessed annually using the RTOG radiation morbidity scoring criteria. | three years | 
| Quality of life through study completion, up to 3 years | Evaluated with questionnaire of EuroQoL 5 dimension, 5 level health state utility index (EQ-5D-5L). | up to three-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locoregional relapse, nasopharyngeal carcinoma, chemoradiotherapy, PD-1 antibody, efficacy, toxicity