Induction High-Low Dose Radiotherapy Plus Anti-PD-1 Followed by Definitive Radiotherapy in Recurrent Nasopharyngeal Carcinoma (Single-Arm Phase II) (REDEFINE)

Induction Therapy With High-Low Dose Radiotherapy Combined With Anti-PD-1 Monoclonal Antibody Followed by Definitive Radiotherapy in Recurrent Nasopharyngeal Carcinoma: A Single-Arm, Single-Center Phase II Trial

This single-arm, single-center phase II trial evaluates the safety and efficacy of a non-continuous radio-immunotherapy strategy for recurrent nasopharyngeal carcinoma (NPC) unsuitable for surgery. Induction consists of three fractions of low-dose radiotherapy (1.5 Gy ×3) plus high-dose boosts (5 Gy ×3 to tumor core with carotid/mucosal sparing) combined with anti-PD-1 (240 mg IV on Day 1 and Day 22). After a 21-28-day interval, definitive IMRT (2 Gy ×28, 5 days/week) is delivered without concurrent immunotherapy to minimize immune damage. Anti-PD-1 maintenance (240 mg IV Q3W) starts within 2 weeks after radiotherapy for up to 12 months or until progression/toxicity. The primary endpoint is ORR at 3 months post-radiotherapy; secondary endpoints include 3-year OS, 3-year PFS, safety (NCI-CTCAE v5.0), and quality of life (EORTC QLQ-C30). Key eligibility: histologically confirmed non-keratinizing NPC (WHO II/III), rT2-rT4, ECOG 0-1, adequate organ function.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma (NPC); Recurrent Nasopharyngeal Neoplasms
• Intervention / Treatment: Radiation: High-Low Dose Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingao Li Prof. Jingao Li, MD; Phone Number: 8613970866296; Email: ndzhlyy0005@ncu.edu

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Recruiting
      • Jiangxi Cancer Hospital
      • Contact: Tianzhu Lu, PhD; Phone Number: 13874877311; Email: lutianzhu2008@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria：

Histologically confirmed non-keratinizing NPC (WHO II/III); local (± regional) recurrence ≥1 year after prior radical therapy; surgery-ineligible;

rT2-rT4 (AJCC 8th); ECOG 0-1;

Adequate organ function (hematologic, hepatic, renal, coagulation per protocol thresholds);

Contraception requirements per protocol; signed informed consent.

Exclusion Criteria：

Distant metastasis at recurrence; active necrosis at recurrence; active/previous autoimmune disease; prior PD-1/PD-L1 therapy; uncontrolled comorbidities; active infections (HBV/HCV/HIV criteria per protocol); interstitial lung disease/pneumonitis; pregnancy/lactation; other protocol-specified exclusions.

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
Experimental: Induction High-Low Dose RT + Anti-PD-1 → Definitive RT → Anti-PD-1 Maintenance; Induction: LD-RT 1.5 Gy ×3 (D1-D3) + HD boost 5 Gy ×3 to tumor core; Anti-PD-1 240 mg IV on D1 & D22. Definitive RT: from ~D28, IMRT 2 Gy ×28 (5 days/week) without concurrent IO. Maintenance: Anti-PD-1 240 mg IV Q3W up to 12 months. Early stop if CR at 50 Gy or ulcer occurs per protocol.	Radiation: High-Low Dose Radiotherapy; Induction LD-RT 1.5 Gy ×3 (full lesion coverage) + HD boost 5 Gy ×3 (tumor core; carotid/mucosa sparing <3 Gy/fx); followed by definitive IMRT 2 Gy ×28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate (ORR) at 3 months post-radiotherapy	3 months after completion of definitive radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival (OS) - Time from treatment start to death from any cause;	3 years.
Progression-Free Survival	Time from treatment start to progression or death;	3 years.
Safety	Incidence and grade of adverse events per NCI-CTCAE v5.0;	through 12 months of therapy and 3-year follow-up.

Collaborators and Investigators

• Sponsor: Jiangxi Provincial Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 30, 2025
• First Submitted That Met QC Criteria: November 30, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: November 30, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: PD-1 inhibitor; re-irradiation; recurrent NPC; high-low dose radiotherapy; induction radio-immunotherapy
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
• Other Study ID Numbers: REDEFINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No