PD-1 Monoclonal Antibody Combined With Gemcitabine and Cisplatin Followed by Selective Radiotherapy for Unresectable Locally Recurrent NPC

PD-1 Monoclonal Antibody Combined With Gemcitabine and Cisplatin Followed by Selective Radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma: A Multicenter, Prospective, Single-Arm Phase II Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy

Detailed Description

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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• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 2

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. Local recurrence (with or without regional recurrence) more than one year after radical treatment and unsuitable for surgery.
3. Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO type II or III).
4. Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
5. ECOG performance status 0-1.
6. Expected survival ≥ 3 months.
7. No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent nasopharyngeal carcinoma
8. No contraindications to immunotherapy, chemotherapy, or re-irradiation.

9. 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

10. 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. Presence of grade 3 or higher late radiation toxicity (excluding skin, subcutaneous tissue, and mucosa) at the time of recurrence
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 ≥ 1000 copies/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 treatment initiation to the date of death due to any cause.	3 years

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2026
• Primary Completion (Estimated): April 10, 2032
• Study Completion (Estimated): April 10, 2035

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): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 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