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

Jiangxi Provincial Cancer Hospital

Status and phase: Enrolling; Phase 2

Conditions: Recurrent Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma (NPC)

Treatments: Radiation: High-Low Dose Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07277764

REDEFINE

Details and patient eligibility

About

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.

Enrollment: 23 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

23 participants in 1 patient group

Induction High-Low Dose RT + Anti-PD-1 → Definitive RT → Anti-PD-1 Maintenance

Experimental group

Description:

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.

Treatment:

Radiation: High-Low Dose Radiotherapy