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

NCT ID: NCT07320690

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

356 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2031-07-01

Brief Summary

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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.

Detailed Description

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Conditions

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Squamous Cell Carcinoma of the Head and Neck

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants are randomized 1:1 to downgraded surgery (experimental) or standard surgery (control).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open-label study; no parties are masked.

Study Groups

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De-escalation surgery

The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy.

Group Type EXPERIMENTAL

De-escalation surgery

Intervention Type PROCEDURE

Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.

radiotherapy

Intervention Type RADIATION

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.

adjuvant immunotherapy

Intervention Type DRUG

Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.

Standard Surgery

The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy.

Group Type ACTIVE_COMPARATOR

Standard Surgery

Intervention Type PROCEDURE

Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.

radiotherapy

Intervention Type RADIATION

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.

adjuvant immunotherapy

Intervention Type DRUG

Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.

Interventions

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De-escalation surgery

Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.

Intervention Type PROCEDURE

Standard Surgery

Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.

Intervention Type PROCEDURE

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.

Intervention Type RADIATION

adjuvant immunotherapy

Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.

Intervention Type DRUG

Other Intervention Names

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postoperative adjuvant immunotherapy

Eligibility Criteria

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Inclusion Criteria

1. Age between 18 and 75 years inclusive, with no restriction on gender.
2. Histologically confirmed primary squamous cell carcinoma of the head and neck (excluding nasopharyngeal carcinoma).
3. Clinical stage III-IVa according to the AJCC 8th edition TNM staging system prior to immunotherapy; specifically, stage III-IVa for oropharyngeal squamous cell carcinoma (p16-negative) or stage III for oropharyngeal squamous cell carcinoma (p16-positive).
4. ECOG performance status of 0 or 1.
5. Life expectancy of ≥6 months.
6. Received preoperative immune checkpoint inhibitor therapy, primarily with anti-PD-1 monoclonal antibodies or bispecific antibodies containing an anti-PD-1 arm, regardless of brand, with or without concurrent chemotherapy or targeted therapy, for no more than six cycles.
7. Achieved complete response (CR) or partial response (PR) on imaging assessment after preoperative therapy, according to RECIST 1.1 criteria.
8. Assessed as eligible for de-escalation surgery based on clinical evaluation by the surgeon. Examples include omission of surgery on the primary lesion; preservation of critical structures or functions, such as retaining the mandible initially planned for resection; avoidance of flap reconstruction; or limitation of tongue resection to less than half when hemi-glossectomy was initially indicated.
9. No prior curative surgery or radiotherapy for the current tumor.
10. Willing to undergo surgical treatment.
11. No significant contraindications to surgery.
12. Voluntary participation in the study, signed informed consent, good compliance, and willingness to cooperate with follow-up visits.

Exclusion Criteria

1. Severe underlying diseases making the patient unable to tolerate surgery.
2. Current tumor is recurrent.
3. Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, or symptomatic congestive heart failure within 6 months before randomization.
4. History of psychiatric drug abuse or drug addiction.
5. Pregnant or breastfeeding women.
6. Diagnosis of other malignancies within 5 years prior to study entry, except for locally treated and cured basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder carcinoma, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
7. Any other severe physical or mental illness, or laboratory abnormalities that might increase the risk associated with participation or interfere with the study results, or any other conditions deemed unsuitable for participation by the investigator.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

OTHER

Sponsor Role lead

Responsible Party

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Yue He, MD

Director of Oral and Maxillofacial & Head and Neck Oncology Department , Principal Investigator, Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Shanghai Ninth Peolple's Hospital

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

Central Contacts

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Yue He, M.D.

Role: CONTACT

+8613501950200

Feng Liu, M.D.

Role: CONTACT

+8618917797783

Other Identifiers

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NCRCO2025ZD-01

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

JYKQ-2025-057

Identifier Type: -

Identifier Source: org_study_id

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