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This trial aim to explore whether short-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 3 cycles of 400 mg q6w in the consolidation phase) yields non-inferior event-free survival compared to long-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 5 cycles of 400 mg q6w in the consolidation phase) in patients with locoregionally advanced nasopharyngeal carcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant) | Experimental | Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles. |
|
| tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant) | Active Comparator | Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tislelizumab | Drug | Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 3 cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Failure-free survival (FFS) | From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | From date of randomization until the date of death from any cause, whichever came first | 3 years |
| Distant metastasis-free survival (DMFS) | From date of randomization until the date of first documented distant metastasis, whichever occurred first |
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Inclusion Criteria:
Age ≥18 and ≤65 years
Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
Eastern Cooperative Oncology Group performance score of 0-1.
Tumor staged as T4N1 and T1-4N2-3 disease (AJCC 9th edition).
Adequate marrow function:
white blood cell count > 4 × 10⁹/L hemoglobin >90g/L and platelet count >100×10⁹/L
Adequate hepatic and renal function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN, Alkaline phosphatase ≤ 2.5 ×ULN, clearance rate ≥ 60 ml/min 7. Other laboratory and clinical criteria Normal: thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG); For patients aged >50 years with a history of smoking, normal pulmonary function test (PFT) results are required; For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any exclusion criteria listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits.
8. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.
9. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jun Ma | Contact | +862087343469 | majun2@mail.sysu.edu.cn | |
| Yelin Liang | Contact | +862087342370 | liangyl@sysucc.org.cn |
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| tislelizumab | Drug | Neoadjuvant tislelizumab 200 mg, every 3 weeks for 3 cycles; Adjuvant tislelizumab 400 mg, every 6 weeks for 5 cycles. |
|
| Gemcitabine + cisplatin (GP) | Drug | neoadjuvent gemcitabine (1000 mg/m2 d1, d8) and cisplatin (80 mg/m2 d1) every 3 weeks for 3 cycles |
|
| Cisplatin (100mg/m2) | Drug | Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation |
|
| intensity-modulated radiotherapy | Radiation | Defnitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions. |
|
| 3 years |
| Locoregional recurrence-free survival (LRRFS) | From date of randomization until the date of first documented locoregional recurrence, whichever occurred first | 3 years |
| Adverse events (AEs) | Graded according to CTCAE V5.0 | within 5 years |
| Quality of life (QoL) | The EORTC QoL questionnaire-C30 (EORTC QLQ-C30)version 3.0 will be used.The change of QoL from randomization to 9 weeks (at the end of neoadjuvant treatment), 16 weeks (at the end of radiotherapy), 28 weeks (at the 3nd cycle of adjuvant tislelizumab treatment), 40 (at the 5nd cycle of adjuvant tislelizumab treatment, if available), 1 year, 2 years, 3 years, 4 years, and 5 years after randomization. This questionnaire comprises 30 questions, 24 aggregated into nine multi-question scales: five functioning scales (e.g., physical), three symptom scales (e.g., fatigue), and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual of EORTC QLQ-C30. | week 0, 9, 16, 28, 40 and 1 year, 2 years, 3 years, 4 years, and 5 years after randomization |
| cost-effectiveness analysis | Cost-effectiveness will be evaluated as the incremental cost per clinical outcome achieved (e.g., cost per quality-adjusted life year gained or cost per event avoided) when comparing the intervention and control groups. | 3 years |
| ID | Term |
|---|---|
| D009303 | Nasopharyngeal Neoplasms |
| ID | Term |
|---|---|
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009302 | Nasopharyngeal Diseases |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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| ID | Term |
|---|---|
| C000707970 | tislelizumab |
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| D050397 | Radiotherapy, Intensity-Modulated |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D020266 | Radiotherapy, Conformal |
| D011881 | Radiotherapy, Computer-Assisted |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
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