Nasopharyngeal Cancinoma (NPC)
Conditions
Brief summary
Re-irradiation is the most common clinical treatment for recurrent nasopharyngeal carcinoma; however, it is associated with severe complications which seriously affect patients' quality of life. Exploring deferred salvage radiotherapy until nasopharyngeal or cervical progression after PD 1 plus GP chemotherapy and immunotherapy maintenance is of great significance for improving the long-term survival and quality of life of patients with unresectable locally recurrent NPC. Thus, the investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial to evaluate the efficacy and safety of maintenance Immunotherapy with deferred salvage radiotherapy with an objective response to chemoimmunotherapy in patients with unresectable locally recurrent NPC .
Detailed description
Re-irradiation is the most common clinical treatment for recurrent nasopharyngeal carcinoma; however, it is associated with severe complications (such as radiation-induced nasopharyngeal necrosis, radiation encephalopathy, trismus, profound hearing loss, and cervical muscle stiffness), which seriously affect patients' quality of life. The addition of immunotherapy plays an important role in disease control for recurrent or metastatic NPC (RM-NPC) and PD-1 antibody plus gemcitabine-cisplatin (GP) chemotherapy has become the current standard of care for the first-line treatment of RM-NPC. Exploring deferred salvage radiotherapy until nasopharyngeal and/or cervical progression after PD 1 plus GP chemotherapy and immunotherapy maintenance is of great significance for improving the long-term survival and quality of life of patients with unresectable locally recurrent NPC. Thus, the investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial to evaluate the efficacy and safety of of maintenance Immunotherapy with deferred salvage radiotherapy with an objective response to chemoimmunotherapy in patients with unresectable locally recurrent NPC .
Interventions
DRUGMaintenance Immunotherapy With Deferred Salvage Radiotherapy
1. Gemcitabine + Cisplatin Chemotherapy: Gemcitabine 1000 mg/m² on days 1 and 8 + Cisplatin 80 mg/m² on day 1, every 3 weeks, for 4-6 cycles. PD-1 Monoclonal Antibody Immunotherapy: 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, for 4-6 cycles. 2. PD-1 Maintenance Therapy: 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 is confined to the nasopharynx and/or neck without new metastatic lesions, salvage radiotherapy to these regions will be given, followed by continued immunotherapy maintenance until further progression), unacceptable toxicity, withdrawal of patient consent, or completion of a cumulative 2 years of treatment.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years, any gender. 2. primary tumour recurrent T classificationT2-T4, regional lymph nodes recurrent N classificationN0-N2, no distant metastasis (recurrent M0); overall recurrent stage II-III according to the American Joint Committee on Cancer Union for International Cancer Control 9th edition stage-classification system. 3. Local recurrence (with or without regional recurrence) more than one year after radical treatment and unsuitable for surgery. 4. Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO type II or III). 5. Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy. 6. ECOG performance status 0-1. 7. Expected survival ≥ 3 months. 8. No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent nasopharyngeal carcinoma 9. No contraindications to immunotherapy, chemotherapy, or re-irradiation. 10. 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 ≥ 50 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN. 11. 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
1. known pre-existing radiation-induced complications, including soft tissue necrosis, brain injury, neck fibrosis, or other radiation-induced complications of grade 3 or above 2. Prior anti-tumor therapy for recurrent nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy. 3. Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors. 4. History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer. 5. Active autoimmune disease or history of autoimmune disease requiring systemic treatment (e.g., corticosteroids, immunosuppressants) within the past 2 years, except for stable hypothyroidism, type 1 diabetes mellitus, or resolved childhood asthma/atopy. 6. Known history of active pulmonary tuberculosis (TB). Suspected active TB must be excluded by chest X-ray, sputum examination, and assessment of clinical signs and symptoms. 7. Hepatitis B: HBsAg positive with peripheral blood HBV DNA more than 1000 copies/mL or 200 IU/mL 8. Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative 9. HIV infection 10. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia). 11. Interstitial lung disease, non-infectious pneumonitis, or history of ≥ grade 2 pneumonitis. 12. Major surgery within 4 weeks before enrollment, or unhealed surgical wound. 13. Pregnant or breastfeeding women, or those planning pregnancy during the study period. 14. Known allergy or hypersensitivity to study drugs or their excipients. 15. Any condition that, in the investigator's judgment, would interfere with trial participation or interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3 years | the time from the date of maintenance treatment initiation to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free-survival | 3 years | the time from the date of maintenance treatment initiation to the first objectively documented disease progression, or death from any cause, whichever occurs first. |
| Locoregional progression-free survival | 3 years | the time from the date of maintenance treatment initiation to the occurrence of a locoregional progression |
| Distant progression-free survival | 3 years | the time from the date of maintenance treatment initiation to the occurrence of a distant progression. |
| Incidence of acute and late toxicity | 3 years | Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 6.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. |
| Quality of life (QoL) | 3 years | Assessed using the EORTC QLQ-C30 (v3.0) |
Countries
China
Contacts
CONTACTHaiqiang Mai
Outcome results
None listed