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
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 94
- Locations
- 1
- Primary Endpoint
- Overall survival
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-70 years, any gender.
- •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-
- •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 ≥ 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
Exclusion Criteria
- •Presence of grade 3 or higher late radiation toxicity (excluding skin, subcutaneous tissue, and mucosa) at the time of recurrence
- •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 ≥ 1000 copies/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).
Arms & Interventions
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.
Intervention: Selective re-irradiation (Radiation)
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.
Intervention: Immediate re-irradiation (Radiation)
Outcomes
Primary Outcomes
Overall survival
Time Frame: 3 year
the time from the date of randomization to the date of death due to any cause.
Secondary Outcomes
- Progression free-survival(3 year)
- Progression free-survival 2(3 year)
- Distant progression-free survival(3 year)
- Locoregional progression-free survival(3 year)
- Incidence of Acute and Late Toxicity(3 year)
- Quality of life (QoL)(3 year)
Investigators
Hai-Qiang Mai,MD,PhD
Principal Investigator
Sun Yat-sen University