Toripalimab Plus Concurrent Chemo-radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma

A Multicenter Randomized Clinical Phase 3 Trial of Toripalimab Plus Concurrent Chemo-radiotherapy vs Concurrent Chemo-radiotherapy Alone for Unresectable Locally Recurrent Nasopharyngeal Carcinoma

Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that concurrent and adjuvant PD-1 treatment added to concurrent chemo-radiotherapy could further decrease the rate of disease progression and improve the survival outcome of patients with unresectable locally recurrent nasopharyngeal carcinoma compared with those treated with concurrent chemo-radiotherapy alone.

Through multicenter, open-label, randomised clinical trials, patients with unresectable locally recurrent nasopharyngeal carcinoma are randomized into concurrent chemo-radiotherapy plus concurrent and adjuvant PD-1 treatment group and concurrent chemo-radiotherapy alone group. The efficacy and safety of patients between these two groups are compared.

Inclusion Criteria:

1. Histologically confirmed recurrent nasopharyngeal carcinoma.

2. The recurrence time is more than 12 months from the end of the first course of radiotherapy.

3. Tumor staged as rT2-4N0-3M0，rII-IVa (according to the 8th AJCC edition).

4. Subjects must have a measurable disease by CT or MRI per RECIST 1.1 criteria.

5. Karnofsky scale (KPS)≥70.

6. Normal bone marrow function.

7. Normal liver and kidney function:

   1. total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal limit;
   2. creatinine clearance rate of at least 60 mL/min or creatinine of no more than 1.5 times the upper normal limit.

8. Given written informed consent.

Exclusion Criteria:

1. Resectable nasopharyngeal diseases: rT2 (the tumour is confined in the superficial parapharyngeal spacer and is more than 0.5cm from the internal carotid artery) and rT3 (the tumour is confined in the base wall of the sphenoid sinus and is more than 0.5cm from the internal carotid artery and cavernous sinus).
2. The patients are suffering from severe nasopharyngeal necrosis, radiation induced brain injury, and fibrosis of the neck et. al, who are evaluated as unsuitable for secondary radiotherapy by the researchers.
3. Has known allergy to large molecule protein products or any compound of study therapy.
4. Has known subjects with other malignant tumors.
5. Has any active autoimmune disease or history of autoimmune disease.
6. Has a history of psychiatric substance abuse, alcoholism, or drug addiction.
7. The laboratory examination value does not meet the relevant standards within 7 days before enrollment
8. Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study medication.
9. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year.
10. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.
11. 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.
12. Has a known history of human immunodeficiency virus (HIV).
13. Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive
14. Has received a live vaccine within 4 weeks of planned start of study therapy
15. Pregnancy or breast feeding