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

Official title

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

Overview

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

• Drug Maintenance 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 da

Primary outcome measures

• Overall survival [Time frame: 3 years]

Secondary outcome measures (6)

• Progression free-survival [Time frame: 3 years]
• Locoregional progression-free survival [Time frame: 3 years]
• Distant progression-free survival [Time frame: 3 years]
• Incidence of acute and late toxicity [Time frame: 3 years]
• Quality of life (QoL) [Time frame: 3 years]
• Quality of life (QoL) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Age 18-70 years, any gender.
• 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.
• 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 ≥ 50 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN.

• 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

• known pre-existing radiation-induced complications, including soft tissue necrosis, brain injury, neck fibrosis, or other radiation-induced complications of grade 3 or above
• Prior anti-tumor therapy for recurrent nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
• Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
• History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer.
• 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.
• 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.
• Hepatitis B: HBsAg positive with peripheral blood HBV DNA more than 1000 copies/mL or 200 IU/mL
• Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative
• HIV infection
• Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia).
• Interstitial lung disease, non-infectious pneumonitis, or history of ≥ grade 2 pneumonitis.
• Major surgery within 4 weeks before enrollment, or unhealed surgical wound.
• Pregnant or breastfeeding women, or those planning pregnancy during the study period.
• Known allergy or hypersensitivity to study drugs or their excipients.
• Any condition that, in the investigator's judgment, would interfere with trial participation or interpretation of results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Fujian Cancer Hospital — Fuzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Guangxi Medical University Cancer Hospital — Nanning
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07528183 · B2025-628

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗