NCT07320690

De-Escalation Surgery After Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

A Randomized Controlled Clinical Study of De-Escalation Surgery Following Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 356 (estimated)
• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, randomized, open-label, non-inferiority clinical trial designed to evaluate whether downgraded surgery-guided by post-immunotherapy tumor boundaries-can achieve comparable 3-year overall survival (OS) to standard surgery in patients with Stage III-IVa locally advanced head and neck squamous cell carcinoma (HNSCC) who have responded to neoadjuvant immunotherapy. A total of 356 patients will be randomized 1:1 to receive either downgraded or standard surgery, followed by risk-adapted adjuvant therapy. The primary endpoint is 3-year OS, with secondary endpoints including disease-free survival, quality of life, complication rates, and cost-effectiveness. The study hypothesizes that downgraded surgery will preserve organ function and quality of life without compromising survival outcomes.

Conditions

• Squamous Cell Carcinoma of the Head and Neck

Interventions

Type	Name	Description
PROCEDURE	De-escalation surgery	Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.
PROCEDURE	Standard Surgery	Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.
RADIATION	radiotherapy	Radiotherapy is recommended within 6 weeks after surgery. Patients achieving a pathological complete response (pCR) may be exempted. For the primary tumor and involved nodes, 60-70 Gy in 30-35 fractions is delivered once daily, Monday to Friday (low risk: 60 Gy; high risk: 66 Gy; residual disease: 70 Gy). Suspected subclinical areas receive 45-50 Gy (2 Gy/f) or 54-63 Gy (1.6-1.8 Gy/f). Concurrent cisplatin is given when extracapsular nodal extension or positive/close margins (\<1 mm) are present: 100 mg/m² every 3 weeks ×3, with renal function-based dose adjustment. For patients unsuitable for cisplatin, cetuximab is administered at 400 mg/m² in the first week, then 250 mg/m² weekly.
DRUG	adjuvant immunotherapy	Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.

Timeline

• Start date: 2026-01-01
• Primary completion: 2031-07-01
• Completion: 2031-07-01
• First posted: 2026-01-06
• Last updated: 2026-01-06

Locations

1 site across 1 country: China