De-Escalation Surgery After Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-Margin)

December 27, 2025 updated by: Yue He, MD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
356

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Shanghai Ninth Peolple's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: De-escalation surgery
The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy.
Procedure: De-escalation surgery
Surgical planning and resection will be conducted based on tumor boundaries assessed after 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.
Other Names:
  • postoperative adjuvant immunotherapy
Active Comparator: Standard Surgery
The surgical procedure should be designed and performed based on the tumor boundaries 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.
Other Names:
  • postoperative adjuvant immunotherapy
Procedure: Standard Surgery
Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
3-year overall survival (OS) rate
Time Frame: 3 years
The proportion of subjects in the intention-to-treat population who are alive at 3 years after randomization.
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
5-year overall survival (OS) rate
Time Frame: 5 years
The proportion of subjects in the intention-to-treat population who are alive at 5 years after randomization.
5 years
3-year and 5-year Event-free survival (EFS) rates
Time Frame: 5 years
The proportion of subjects in the intention-to-treat population who have not experienced any EFS events at 3 and 5 years after randomization. EFS time is defined as the duration from randomization to the first occurrence of any of the following events: (1) disease recurrence or metastasis in patients who underwent surgery; (2) disease progression per RECIST 1.1, or recurrence/metastasis after non-surgical treatment (e.g., radiotherapy) following neoadjuvant therapy; (3) occurrence of a second primary tumor; or (4) death from any cause. Patients who did not undergo surgery due to clinical complete response (CR) or near CR, as well as those who declined surgery but received other antitumor therapies without experiencing progression, recurrence/metastasis, or death, or who had positive surgical margins without radiographic evidence of progression, are not considered to have reached an EFS event.
5 years
incidence of adverse events
Time Frame: Through study completion, an average of 5 years
Adverse events observed will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Through study completion, an average of 5 years
Surgical complications
Time Frame: Perioperative
Surgical complications in this study will be assessed according to the Clavien-Dindo classification system, and detailed information on all complications occurring during the perioperative period will be recorded in the eCRF.
Perioperative
Totally quality of life, QoL
Time Frame: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
Totally Health status and quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Lifer Questionnaire Core 30 (EORTC QLQ-C30) questionnaires.
Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
Quality of life for HNSCC patients
Time Frame: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
Health status and quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Lifer Questionnaire Head and Neck 35 (EORTC QLQ-H&N35) questionnaires
Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pathologic complete response rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients who achieved pCR among the ITT population and the pathologically evaluable population in each group.
Through study completion, an average of 5 years
Major pathologic response rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients who achieved MPR among the ITT population and the pathologically evaluable population in each group.
Through study completion, an average of 5 years
Surgical resection rates stratified by anatomical subsite and extent of surgical downgrading
Time Frame: Through study completion, an average of 5 years
The proportion of patients who received that level of surgery among those initially planned for surgical intervention at the corresponding subsite.
Through study completion, an average of 5 years
Primary tumor surgery exemption rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients who were exempted from primary tumor surgery among the ITT population in that group.
Through study completion, an average of 5 years
Lymph node dissection exemption rate
Time Frame: Through study completion, an average of 5 years
The proportion of participants spared lymph node dissection among those originally planned for the procedure.
Through study completion, an average of 5 years
Blood loss volume
Time Frame: Intraoperative
Intraoperative blood loss volume
Intraoperative
Blood transfusion volume
Time Frame: Intraoperative
Intraoperative blood transfusion volume
Intraoperative
Tracheostomy rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients who underwent tracheostomy among the ITT population in that group.
Through study completion, an average of 5 years
Surgical mortality rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients who died from any cause within 28 days after surgery among the ITT population in that group.
Through study completion, an average of 5 years
Flap reconstruction exemption rate
Time Frame: Through study completion, an average of 5 years
The proportion of patients exempted from free flap reconstruction among those who were initially planned to undergo the procedure within the group.
Through study completion, an average of 5 years
Length of hospital stay
Time Frame: Through study completion, an average of 5 years
Total length of hospital stay was calculated from the day of surgery to the day of discharge (a stay of less than 24 hours was counted as 0.5 day). For patients who did not undergo surgery, the hospital stay was recorded as 0 days.
Through study completion, an average of 5 years
Inpatient surgical costs and radiotherapy/chemotherapy costs
Time Frame: Through study completion, an average of 5 years
Medical costs incurred during the hospitalization for surgery and during postoperative radiotherapy and chemotherapy.
Through study completion, an average of 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 29, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • JYKQ-2025-057
  • NCRCO2025ZD-01 (Other Grant/Funding Number: Shanghai Ninth Peolple's Hospital)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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