PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Selective Re-irradiation for Locally Advanced Recurrent NPC

NCT ID: NCT07332247

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-03
• Study Completion Date: 2035-02-03

Brief Summary

This phase II randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus selective re-irradiation in locally advanced recurrent nasopharyngeal carcinoma. The study aims to determine whether sequential radiotherapy provides additional survival benefit beyond systemic immunochemotherapy.

Detailed Description

Nasopharyngeal carcinoma (NPC) is prevalent in Southern China, and 10~15% of patients experience local recurrence, which presents significant treatment challenges. PD-1 inhibitor plus gemcitabine-cisplatin (GP) has become the standard first-line therapy for recurrent/metastatic NPC. However, the survival benefit of adding sequential re-irradiation after GP + PD-1 in locally advanced recurrent nasopharyngeal carcinoma remains uncertain.This phase II randomized trial aims to compare immediate versus selective re-irradiation following PD-1 inhibitor plus GP in locally advanced recurrent NPC, to determine whether sequential re-irradiation provides additional survival benefit without excessive toxicity.

Conditions

Nasopharangeal Cancer; Recurrent Nasopharynx Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selective re-irradiation group

PD-1 inhibitor maintenance + Selective re-irradiation:

PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck, re-irradiation will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Group Type: OTHER

Selective re-irradiation

Intervention Type: RADIATION

PD-1 inhibitor maintenance + Selective re-irradiation PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck, re-irradiation will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Immediate re-irradiation group

Immediate re-irradiation + PD-1 inhibitor Maintenance:

Re-irradiation will be administered Immediately. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Group Type: OTHER

Immediate re-irradiation

Intervention Type: RADIATION

Immediate re-irradiation + PD-1 inhibitor Maintenance:

Re-irradiation will be administered Immediately. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Interventions

Selective re-irradiation

PD-1 inhibitor maintenance + Selective re-irradiation PD-1 inhibitor maintenance therapy:Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1; if progression occurs in the nasopharynx or neck, re-irradiation will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Intervention Type: RADIATION

Immediate re-irradiation

Immediate re-irradiation + PD-1 inhibitor Maintenance:

Re-irradiation will be administered Immediately. PD-1 inhibitor maintenance therapy: Toripalimab 240 mg IV on day 1 every 3 weeks, or Tislelizumab 200 mg IV on day 1 every 3 weeks, or Camrelizumab 200 mg IV on day 1 every 3 weeks, continued until disease progression (per RECIST v1.1), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Hai-Qiang Mai,MD,PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Haiqiang Mai, PhD, MD

Role: CONTACT

maihq@sysucc.org.cn

+86-020-87343643

Facility Contacts

Haiqiang Mai, PhD, MD

Role: primary

maihq@sysucc.org.cn

00862087343643

Other Identifiers

2025-FXY-205

Identifier Type: -

Identifier Source: org_study_id