PD-1 inhibitor plus chemotherapy followed by immediate versus selective re-irradiation for locally advanced recurrent nasopharyngeal carcinoma

An Open-Label, Randomized Controlled Phase II Clinical Trial of PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Selective Re-irradiation for Locally Advanced Recurrent Nasopharyngeal Carcinoma

This phase II trial tests whether immediate or selective re-irradiation after a good response to PD-1 inhibitor plus gemcitabine-cisplatin helps people with locally advanced recurrent nasopharyngeal carcinoma live longer with acceptable side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07332247 on ClinicalTrials.gov

What this trial studies

This randomized phase II trial enrolls people with non-keratinizing locally advanced recurrent nasopharyngeal carcinoma who achieve a complete or partial response after 4–6 cycles of PD-1 inhibitor combined with gemcitabine–cisplatin. Participants are randomized to receive either immediate re-irradiation or selective re-irradiation based on predefined criteria following systemic immunochemotherapy. The study compares survival outcomes and treatment-related toxicity between the two approaches. It is conducted at Sun Yat-sen University Cancer Center and requires adequate organ function and ECOG performance status 0–1.

Who should consider this trial

Good fit: People aged 18–70 with non-keratinizing locally advanced local recurrence more than one year after prior radical treatment who achieved complete or partial response to 4–6 cycles of PD-1 inhibitor plus gemcitabine–cisplatin, have ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients with distant metastases, poor performance status, keratinizing histology, prior treatment for recurrent disease, or who do not respond to the initial PD-1 plus chemotherapy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the trial could show a way to improve survival after systemic PD-1 plus chemotherapy while limiting unnecessary radiation and its toxicities.

How similar studies have performed: PD-1 inhibitor combined with gemcitabine–cisplatin has shown benefit as first-line therapy for recurrent/metastatic NPC, but the added value of sequential re-irradiation after response is not well established and evidence is limited.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Haiqiang Mai, PhD, MD

Conditions Nasopharangeal Cancer; Recurrent Nasopharynx Carcinoma; Locally Advanced Recurrent Nasopharyngeal Carcinoma