Maintenance Immunotherapy With Deferred Salvage Radiotherapy After Response to Chemoimmunotherapy in Recurrent Nasopharyngeal Carcinoma

Maintenance Immunotherapy With Deferred Salvage Radiotherapy in Patients With an Objective Response to Chemoimmunotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma: A Multicenter Phase 2 Single-Arm Trial

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 .

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: Maintenance Immunotherapy With Deferred Salvage Radiotherapy

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 .

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiqiang Mai; Phone Number: +86-20-87343380; Email: maihq@sysucc.org.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Contact: Qiaojuan Guo; Phone Number: +8615080013157; Email: guoqiaojuan@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Qi Yang; Email: yangqi@sysucc.org.cn
      • Contact: Haiqiang Mai; Phone Number: +86-20-87343380; Email: maihq@sysucc.org.cn
  • Guangxi
    • Nanning, Guangxi, China
      • Not yet recruiting
      • Guangxi Medical University Cancer Hospital
      • Contact: Ling Li; Phone Number: +8615977737210; Email: lingli159@163.com
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Kunyu Yang; Phone Number: 008602783262731; Email: yangkunyu@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Selective re-irradiation group

Drug: PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy; 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.; 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	the time from the date of maintenance treatment initiation to the date of death due to any cause.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Progression free-survival	the time from the date of maintenance treatment initiation to the first objectively documented disease progression, or death from any cause, whichever occurs first.	3 years
Locoregional progression-free survival	the time from the date of maintenance treatment initiation to the occurrence of a locoregional progression	3 years
Distant progression-free survival	the time from the date of maintenance treatment initiation to the occurrence of a distant progression.	3 years
Incidence of acute and late toxicity	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.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): July 22, 2026
• Primary Completion (Estimated): July 22, 2032
• Study Completion (Estimated): July 22, 2034

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine
• Other Study ID Numbers: B2025-628

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No