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This prospective trial aims to enroll patients with stage III-IVA (AJCC 8th,) locoregionally advanced nasopharyngeal carcinoma (LANPC). Under the condition of full course of PD-1/PD-L1 blockades, patients who achieved radiological partial response after 3 cycles of platinum-based chemotherapy plus PD-1/PD-L1 blockades will be randomized in a 1:1 ratio to receive gradient radiotherapy (reducing the irradiation dose of PET-CT areas without metabolic abnormalities, while maintaining adequate irradiation dose of areas with metabolic abnormalities) or standard dose radiotherapy with concurrent chemotherapy. It is expected to provide a new therapeutic option for locally advanced nasopharyngeal carcinoma at moderate risk.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Induction chemotherapy plus conventional concurrent chemoradiotherapy | Active Comparator |
| |
| Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Full course of PD-1/PD-L1 blockades | Drug | a) Camrelizumab 200mg, b) Toripalimab 240mg, or c) Adebrelimab 1200mg will be started on day 1 of induction chemotherapy and given every 3 weeks for up to 12 cycles, or until intolerable toxicity, or disease progression or withdrawal from the treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Progress-Free Survival (PFS) | Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Defined as the time interval from randomization to death due to any cause. | 3 years |
| Locoregional Relapse-Free Survival (LRRFS) | Defined as the time from randomisation to the date of first locoregional relapse. |
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Inclusion Criteria:
Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
Tumor staged as III-IVA (AJCC 8th).
Patients who achieved partial response according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
Eastern Cooperative Oncology Group performance status ≤1.
Age: 18-65 years old.
Adequate organ function:
Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
Adequate liver and kidney function: Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.; creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the upper normal limit.
Patients must be informed of the investigational nature of this study and give written informed consent.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ming-Yuan Chen, MD,PhD | Contact | +86-20-87343361 | chenmy@sysucc.org.cn | |
| Rui You, MD,PhD | Contact | +86-13580439820 | yourui@sysucc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Ming-Yuan Chen, MD,PhD | Sun Yat-sen University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Fifth Affiliated Hospital of Sun Yat-sen University | Recruiting | Zhuhai | Guangdong | 519000 | China |
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|
| Cisplatin-based induction chemotherapy | Drug | Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy. |
|
| Standard-dose IMRT | Radiation | GTVnx/nd:69.96Gy/33Fr/2.12Gy CTV1: 60.60Gy/33Fr/1.82y CTV2: 54.12Gy/33Fr/1.64Gy |
|
| Gradient Fractionated IMRT | Radiation | GTVresidue: 68Gy/30Fr/2.27Gy GTVmcr: 60Gy/30F/2Gy CTV1:54Gy/30F/1.8Gy CTV2: 48GY/30F/1.60Gy |
|
| Concurrent Chemotherapy | Drug | Cisplatin 100mg/m2 every 3 weeks for 2 cycles |
|
| 3 years |
| Distant Metastasis-Free Survival (DMFS) | Defined as the time interval from randomisation to the date of first distant metastases. | 3 years |
| The proportion of patients with treatment related acute complications | The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria. | 1 year |
| The proportion of patients with treatment related late complications | The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria. | 3 years |
| Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) | Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment. | 3 years |
| Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) | 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. | 3 years |
| ID | Term |
|---|---|
| D000077274 | Nasopharyngeal Carcinoma |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009303 | Nasopharyngeal Neoplasms |
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009302 | Nasopharyngeal Diseases |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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| ID | Term |
|---|---|
| D050397 | Radiotherapy, Intensity-Modulated |
| ID | Term |
|---|---|
| D020266 | Radiotherapy, Conformal |
| D011881 | Radiotherapy, Computer-Assisted |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
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