PD-1 Inhibitor Plus Chemotherapy Followed by Immediate Versus Salvage Locoregional Radiotherapy in De Novo Metastatic NPC

NCT ID: NCT07235319

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-20
• Study Completion Date: 2034-11-20

Brief Summary

This phase III randomized trial evaluates PD-1 inhibitor plus chemotherapy followed by immediate versus salvage locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma. The study aims to evaluate whether salvage locoregional radiotherapy is non-inferior to immediate radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with potential for reduced toxicity.

Detailed Description

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China, with approximately 15% of patients presenting with distant metastases at diagnosis. A PD-1 inhibitor combined with gemcitabine and cisplatin (GP) has become the standard first-line therapy for metastatic NPC. However, the survival benefit of adding immediate locoregional radiotherapy to PD-1 inhibitor plus GP in de novo metastatic NPC remains uncertain. This phase III randomized trial is designed to compare immediate versus salvage locoregional radiotherapy following PD-1 inhibitor plus GP in de novo metastatic NPC, with the objective of determining whether salvage radiotherapy is non-inferior to immediate radiotherapy while offering reduced toxicity.

Conditions

Nasopharangeal Cancer; Distant Metastasis

Study Design

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

Study Groups

Immediate locoregional radiotherapy group

Immediate locoregional radiotherapy

Group Type: ACTIVE_COMPARATOR

Immediate locoregional radiotherapy

Intervention Type: RADIATION

Immediate locoregional radiotherapy (LRRT) with concurrent chemotherapy + PD-1 inhibitor Maintenance.

Concurrent chemotherapy:

Cisplatin (DDP) 80mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.

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.

Salvage locoregional radiotherapy group

Salvage locoregional radiotherapy

Group Type: EXPERIMENTAL

Salvage locoregional radiotherapy

Intervention Type: RADIATION

PD-1 inhibitor maintenance + Salvage locoregional radiotherapy

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 while metastatic lesions remain controlled, salvage locoregional radiotherapy* will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

*Concurrent chemotherapy: Cisplatin (DDP) 80 mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.

Interventions

Immediate locoregional radiotherapy

Immediate locoregional radiotherapy (LRRT) with concurrent chemotherapy + PD-1 inhibitor Maintenance.

Concurrent chemotherapy:

Cisplatin (DDP) 80mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.

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

Salvage locoregional radiotherapy

PD-1 inhibitor maintenance + Salvage locoregional radiotherapy

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 while metastatic lesions remain controlled, salvage locoregional radiotherapy* will be administered and PD-1 maintenance will continue until subsequent progression), unacceptable toxicity, patient withdrawal, or a maximum treatment duration of 2 years.

*Concurrent chemotherapy: Cisplatin (DDP) 80 mg/m², starting on day 1 of radiotherapy, administered every 3 weeks during radiotherapy for a total of 3 cycles.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Age 18-70 years, any gender.

2. Histologically confirmed differentiated non-keratinizing carcinoma or undifferentiated non-keratinizing carcinoma by tissue biopsy, with radiologically detectable metastatic lesions. Pathological confirmation of metastatic lesions is recommended but not mandatory.

3. ECOG performance status 0-1.

4. Stage IV NPC according to the 9th edition of the UICC/AJCC staging system.

5. No prior anti-tumor treatment for NPC (radiotherapy, chemotherapy, surgery, etc.).

6. Expected survival ≥ 3 months.

7. At least one measurable lesion per RECIST v1.1.

8. Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.

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. Prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.

2. Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.

3. Presence of uncontrolled or symptomatic central nervous system (CNS) metastases.

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

Hunan Cancer Hospital

Changsha, , China

Site Status: NOT_YET_RECRUITING

Fujian Cancer Hospital

Fuzhou, , China

Site Status: NOT_YET_RECRUITING

Zhejiang Cancer Hospital

Hangzhou, , China

Site Status: NOT_YET_RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, , China

Site Status: NOT_YET_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

Feng Liu, MD, PhD

Role: primary

liufeng@hnca.org.cn

008618613985727

Sufang Qiu, MD, PhD

Role: primary

sufangqiu@fjmu.edu.cn

0086059183660063

Xiaozhong Chen, MD, PhD

Role: primary

chenxiaozhong2016@163.com

0086057188122186

Song Qu, MD, PhD

Role: primary

qusong@sr.gxmu.edu.cn

008607715331422

Other Identifiers

2025-FXY-252

Identifier Type: -

Identifier Source: org_study_id