Nasopharyngeal Carcinoma, Chemotherapy, Radiotherapy, PD-1 Treatment
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGToripalimab plus concurrent chemo-radiotherapy
1. Toripalimab: 240 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of toripalimab are concurrently used during radiotherapy and other 9 cycles of toripalimab are used after the end of radiotherapy. (A total of 11 cycles). 2. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 3. IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy
1. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 2. IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy
Sponsors
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Zhongshan People's Hospital, Guangdong, China
Yuebei People's Hospital
Wuzhou Red Cross Hospital
Fifth Affiliated Hospital, Sun Yat-Sen University
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progress-free survival (PFS) | 3 years | Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Metastasis-Free Survival (DMFS) | 3 years | Defined as the time interval from randomisation to the date of first distant metastases. |
| Locoregional Relapse-Free Survival (LRRFS) | 3 years | Defined as the time from randomisation to the date of first locoregional relapse. |
| Incidence of treatment related acute complications | up to 1 years | The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria. |
| Overall Survival (OS) | 3 years | Defined as the time interval from randomization to death due to any cause. |
| Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) | up to 3 years | Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment. |
| Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) | up to 3 years | Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment. |
| Incidence of treatment related late complications | up to 3 years | The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria. |
Countries
China
Contacts
Primary ContactMing-Yuan Chen, MD, PhD
Backup ContactRui You, MD, PhD
Outcome results
None listed