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The investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial of PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy for unresectable locally recurrent nasopharyngeal carcinoma to evaluate the efficacy and safety of PD-1 antibody plus GP chemotherapy followed by sequential selective radiotherapy in patients with unresectable locally recurrent disease who achieve tumor regression after immunochemotherapy, thereby providing evidence-based medical evidence for the treatment of unresectable locally recurrent NPC and improving treatment outcomes for these patients.
The addition of immunotherapy plays an important role in disease control for recurrent/metastatic nasopharyngeal carcinoma (NPC) and has become an indispensable part of NPC treatment. However, current studies on recurrent/metastatic NPC have enrolled patients with both locally recurrent and metastatic disease, and most patients with recurrence also have distant metastasis, with locally recurrent NPC patients accounting for a very small proportion (JUPITER-02: 13%; CAPTAIN-1st: 0; RATIONALE-309: 3.8%). Due to the high heterogeneity of recurrent/metastatic NPC, patient prognoses vary greatly, and treatment regimens for locally recurrent NPC remain lacking standardization. The investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial of PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy for unresectable locally recurrent nasopharyngeal carcinoma to evaluate the efficacy and safety of PD-1 antibody plus GP chemotherapy followed by sequential selective radiotherapy in patients with unresectable locally recurrent disease who achieve tumor regression after immunochemotherapy, thereby providing evidence-based medical evidence for the treatment of unresectable locally recurrent NPC and improving treatment outcomes for these patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Selective re-irradiation group | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy | Drug |
Toripalimab 240 mg on day 1, every 3 weeks, or Tislelizumab 200 mg on day 1, every 3 weeks, or Camrelizumab 200 mg on day 1, every 3 weeks, until disease progression (according to RECIST v1.1; if progression occurs in the nasopharynx or neck while metastatic lesions remain well controlled, radiotherapy to the nasopharynx and neck will be given, after which immunotherapy maintenance may continue until further progression), unacceptable toxicity, withdrawal of patient consent, or completion of a cumulative 2 years of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | the time from the date of treatment initiation to the date of death due to any cause. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free-survival | the time from the date of treatment initiation to the first objectively documented disease progression, or death from any cause, whichever occurs first. | 3 years |
| Locoregional progression-free survival |
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Inclusion Criteria:
Age 18-70 years, any gender.
Local recurrence (with or without regional recurrence) more than one year after radical treatment and unsuitable for surgery.
Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO type II or III).
Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
ECOG performance status 0-1.
Expected survival ≥ 3 months.
No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent nasopharyngeal carcinoma
No contraindications to immunotherapy, chemotherapy, or re-irradiation.
Adequate organ function within 14 days before first dose, defined as:
Hematology:Hemoglobin ≥ 90 g/L,ANC ≥ 1.5 × 10⁹/L,Platelet count ≥ 100 × 10⁹/L Renal Function:Creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) / eGFR ≥ 60 mL/min Liver Function:Total bilirubin ≤ 1.5 × ULN,AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN in the presence of liver metastases
INR or PT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range,APTT ≤ 1.5 × ULN, unless on therapeutic anticoagulation and values within therapeutic range.
Exclusion Criteria:
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|
the time from the date of treatment initiation to the occurrence of a locoregional progression
| 3 years |
| Distant progression-free survival | the time from the date of treatment initiation to the occurrence of a distant progression. | 3 years |
| Incidence of toxicity | Assessed using CTCAE v5.0 | 3 years |
| Quality of life (QoL) | Assessed using the EORTC QLQ-C30 (v3.0) | 3 years |
| Quality of life (QoL) | Assessed using the EORTC QLQ-H&N35 (v1.0) | 3 years |
| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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