PD-1 Antibody Combined With Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients

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

Official Title
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PD-1 Antibody Combined With Chemoradiotheapy vs. Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients: a Multicenter, Randomised Controlled, Phase III Clinical Trial

Conditions
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Recurrent Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: PD-1 blocking antibody
* Drug: GP
* Radiation: IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment; Not suitable for surgery; Newly histologic diagnosis of NPC (WHO II/III); Clinical stage rII-IVa (AJCC/UICC 8th); ECOG 0-1 point; No treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy; No contraindications to immunotherapy or radiotherapy; 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 ≥10E4copiers/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: PD-1 antibody plus chemoradiotherapy<br>Patients randomized to this arm will receive three cycles of PD-1 antibody (JS001, 240mg every three weeks) combined with GP chemotherapy, then receive IMRT and PD-1 antibody maintenance for eight cycles. | Drug: PD-1 blocking antibody<br>* Toripalimab 240mg, D1, every 3 weeks per cycle<br>* Other names: JS001;Drug: GP<br>* Gemcitabine 1.0g/m2, D1 and D8; Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles<br>Radiation: IMRT<br>* IMRT 60-66Gy, 1.8-2.0Gy/f/day<br>|
| Active Comparator: Chemoradiotherapy<br>Patients randomized to this arm will receive three cycles of GP chemotherapy, then receive IMRT alone. | Drug: GP<br>* Gemcitabine 1.0g/m2, D1 and D8; Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles<br>Radiation: IMRT<br>* IMRT 60-66Gy, 1.8-2.0Gy/f/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From date of randomisation to death | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | From date of randomisation to disease progression | 3 years | 
| Short-term effects | Patient's objective response rate | through study completion, an average of 2 months | 
| Rate of patients with acute toxicities | Evaluating with CTCAE v5.0 | through study completion, an average of 2 months | 
| Quality of life: EuroQoL 5 dimension | Evaluating with questionnaire of EuroQoL 5 dimension, 5 level health state utility index (EQ-5D-5L) | through whole study, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1 antibody, Intensity-modulated Radiation Therapy, Efficacy, Adverse effect, chemotherapy