Squamous Cell Carcinoma of the Head and NeckPhase 3Neo-MarginNCT07320690
De-Escalation Surgery After Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma
A Phase 3 study testing De-escalation surgery, Standard Surgery and radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- De-escalation surgery, Standard Surgery and radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 356 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2026to 1 Jul 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years inclusive, with no restriction on gender.
- Histologically confirmed primary squamous cell carcinoma of the head and neck (excluding nasopharyngeal carcinoma).
- 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).
- ECOG performance status of 0 or 1.
- Life expectancy of ≥6 months.
- 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.
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- Achieved complete response (CR) or partial response (PR) on imaging assessment after preoperative therapy, according to RECIST 1.1 criteria.
- 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.
- No prior curative surgery or radiotherapy for the current tumor.
- Willing to undergo surgical treatment.
- No significant contraindications to surgery.
- Voluntary participation in the study, signed informed consent, good compliance, and willingness to cooperate with follow-up visits.
Who cannot join
- Severe underlying diseases making the patient unable to tolerate surgery.
- Current tumor is recurrent.
- Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, or symptomatic congestive heart failure within 6 months before randomization.
- History of psychiatric drug abuse or drug addiction.
- Pregnant or breastfeeding women.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Ninth Peolple's Hospital
Shanghai, Shanghai Municipality, 200000
About this study
Official title: 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.
- Being tested
- De-escalation surgery, Standard Surgery, radiotherapy, adjuvant immunotherapy
- Keywords
- Head and Neck Squamous Cell Carcinoma, Locally advanced, De-escalation surgery, Standard surgery, Immunotherapy
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
De-escalation surgeryProcedure or surgery
Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy.
Standard SurgeryProcedure or surgery
Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy.
radiotherapyRadiation
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 immunotherapyDrug
Also called postoperative adjuvant immunotherapy
Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications.
| Study group | Role | What they receive |
|---|---|---|
| De-escalation surgery | Experimental | The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy. Receives: Procedure: De-escalation surgery; Radiation: radiotherapy; Drug: adjuvant immunotherapy |
| Standard Surgery | Active comparator | The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy. Receives: Procedure: Standard Surgery; Radiation: radiotherapy; Drug: adjuvant immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year overall survival (OS) rate
The proportion of subjects in the intention-to-treat population who are alive at 3 years after randomization.
Measured: 3 years
Secondary outcomes (6)
5-year overall survival (OS) rate
The proportion of subjects in the intention-to-treat population who are alive at 5 years after randomization.
Measured: 5 years
3-year and 5-year Event-free survival (EFS) rates
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.
Measured: 5 years
incidence of adverse events
Adverse events observed will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Measured: Through study completion, an average of 5 years
Surgical complications
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.
Measured: Perioperative
Totally quality of life, QoL
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.
Measured: 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
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
Measured: Baseline, 1 months (±7d) after surgery and prior to radiotherapy, 2 months after radiotherapy, and 6 months (±14d) after randomization, 1year (±14d) after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2026
- Study start1 Jan 2026 (estimated)
- Primary completion1 Jul 2031 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized 1:1 to downgraded surgery (experimental) or standard surgery (control).
- Masking
- None (open label)
- Enrolment
- 356 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yue He, MD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07320690
- Sponsor's protocol ID
- JYKQ-2025-057
- Other IDs
- NCRCO2025ZD-01
- Acronym
- Neo-Margin
- Status last verified
- Dec 2025
- First submitted
- 29 Nov 2025
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Clinical Study of De-Escalation Surgery Following Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07320690
- Acronym / sponsor ID
- Neo-Margin / JYKQ-2025-057
- Keywords
- Head and Neck Squamous Cell Carcinoma, Locally advanced, De-escalation surgery, Standard surgery, Immunotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 356 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- 1 Jul 2031 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 6 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants are randomized 1:1 to downgraded surgery (experimental) or standard surgery (control).
| Arm | Type | Receives |
|---|---|---|
| De-escalation surgery | Experimental | Procedure: De-escalation surgery, Radiation: radiotherapy, Drug: adjuvant immunotherapyThe surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy. |
| Standard Surgery | Active comparator | Procedure: Standard Surgery, Radiation: radiotherapy, Drug: adjuvant immunotherapyThe surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age between 18 and 75 years inclusive, with no restriction on gender.
- Histologically confirmed primary squamous cell carcinoma of the head and neck (excluding nasopharyngeal carcinoma).
- 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).
- ECOG performance status of 0 or 1.
- Life expectancy of ≥6 months.
Key exclusion criteria (7 listed)
- Severe underlying diseases making the patient unable to tolerate surgery.
- Current tumor is recurrent.
- Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, or symptomatic congestive heart failure within 6 months before randomization.
- History of psychiatric drug abuse or drug addiction.
- Pregnant or breastfeeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| De-escalation surgerySurgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy. | Procedure or surgery | De-escalation surgery |
| Standard SurgerySurgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy. | Procedure or surgery | Standard Surgery |
| radiotherapyRadiotherapy 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. | Radiation | De-escalation surgery, Standard Surgery |
| adjuvant immunotherapyAlso: postoperative adjuvant immunotherapyPostoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications. | Drug | De-escalation surgery, Standard Surgery |
Primary outcome
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.
6 secondary outcomes
5-year overall survival (OS) rate
Time frame: 5 years
3-year and 5-year Event-free survival (EFS) rates
Time frame: 5 years
incidence of adverse events
Time frame: Through study completion, an average of 5 years
Surgical complications
Time frame: 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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing De-escalation surgery, Standard Surgery and radiotherapy in people with Squamous Cell Carcinoma of the Head and Neck, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yue He, M.D. (+8613501950200, HEY1683@sh9hospital.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year overall survival (OS) rate (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.