IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of intensity-modulated radiation therapy combined with toripalimab in patients with the unresectable locally recurrent nasopharyngeal carcinoma.

Detailed Description
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This is an open-label ,single center ,non-randomized, single arm exploratory study. All eligible patients presented with non-keratinizing NPC and stage rT0-4N1-3M0 /rT2-4N0M0 are assigned to receive IMRT combined with toripalimab.

Official Title
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A Single Center 、Single Arm Phase I/II Clinical Trial of Intensity-modulated Radiotherapy Combined With Toripalimab in the Treating of Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Conditions
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Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms, Nasopharyngeal Diseases, Head and Neck Neoplasm

Intervention / Treatment
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* Drug: Tolipalimab
* Radiation: Reirradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Recurrent Nasopharyngeal Carcinoma ( the recurrence time was more than 12 months from the end of the first course of radiotherapy) Patients with histologically confirmed nasopharyngeal carcinoma(WHO type II-III) Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria; Can provide either a newly obtained or archival tumor tissue sample. Tumor staged as rT0-4N1-3M0 or T2-4N0M0，II-IVa (according to the 8th AJCC edition). 18 Years to 65 Years Eastern Cooperative Oncology Group performance status ≤1 Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula). Life expectancy ≥ 3months Subjects must be willing to participate in the research and sign an informed consent form (ICF) Female of child bearing potential, a negative urine or serum pregnancy test result within 72 h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 60 days after the last dose of Toripalimab. Male subjects with WOCBP partner must be willing to use adequate contraception for the course of the study through 120 days after the last dose of Toripalimab. Exclusion Criteria: operable recurrence of nasopharyngeal cancer: rT1N0M0 rT2N0M0 (the tumour was confined in the superficial parapharyngeal spacer) rT3N0M0 (the tumour was confined in the base wall of the sphenoid sinus) rT0N1-3M0 (the tumour was not invasion into the cervical vertebrae, brachial plexus, deep muscles of the neck, or carotid artery) Has known allergy to large molecule protein products or any compound of study therapy Has known Subjects with other malignant tumors Has any active autoimmune disease or history of autoimmune disease Has a history of psychiatric substance abuse, alcoholism, or drug addiction; the laboratory examination value does not meet the relevant standards within 7 days before enrollment Received a systematic Glucocorticoid therapy within 4 weeks of the first dose of study medication. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent; Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy) Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll. Has a known history of human immunodeficiency virus (HIV). Has hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive Has received a live vaccine within 4 weeks of planned start of study therapy Pregnancy or breast feeding

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab +Radiotherapy<br>Radiotherapy, intensity-modulated radiation therapy (IMRT), 60 Gy 2.2Gy per fraction ,5 fractions per week, for 6 weeks. Radiation begun the day after the first dose of Toripalimab. Toripalimab (240mg dose every 3 weeks for 7 cycles, one cycle is three weeks ) will be administered as an intravenous infusion over 60 minutes. | Drug: Tolipalimab<br>* Radiation begun the day after the first dose of Toripalimab. Toripalimab (240mg dose every 3 weeks for 7 cycles, one cycle is three weeks) will be administered as an intravenous infusion over 60 minutes.<br>* Other names: JS001;Radiation: Reirradiation<br>* intensity-modulated radiation therapy (IMRT), 60 Gy 2.2Gy per fraction ,5 fractions per week, for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective Response Rate | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-Free Survival is defined as time interval from recruitment to tumor progression or censoring. | up to 3 years | 
| OS | Overall Survival is defined as time interval from recruitment to all-caused death or censoring. | up to 3 years | 
| Incidence of Treatment-Emergent Adverse Events | Adverse events (AE), Serious Adverse Event(SAE) | Through study completion, an average of half a year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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toripalimab, IMRT, Intensity-Modulated Radiation Therapy, PD-1