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

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

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07277764

Acronym

REDEFINE

Enrollment

Registered

2025-12-11

Start date

2025-10-10

Completion date

2029-12-31

Last updated

2025-12-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nasopharyngeal Carcinoma (NPC), Recurrent Nasopharyngeal Neoplasms

Keywords

recurrent NPC, re-irradiation, high-low dose radiotherapy, induction radio-immunotherapy, PD-1 inhibitor

Brief summary

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.

Interventions

RADIATIONHigh-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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

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

Countries

China

Contacts

Primary ContactJingao Li Prof. Jingao Li, MD

ndzhlyy0005@ncu.edu8613970866296

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026