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| ID | Type | Description | Link |
|---|---|---|---|
| NCRCO2025ZD-01 | Other Grant/Funding Number | Shanghai Ninth Peolple's Hospital |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| De-escalation surgery | Experimental | The surgical procedure should be designed and performed based on the tumor boundaries following neoadjuvant therapy. |
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| Standard Surgery | Active Comparator | The surgical procedure should be designed and performed based on the tumor boundaries prior to neoadjuvant therapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| De-escalation surgery | Procedure | Surgical planning and resection will be conducted based on tumor boundaries assessed after neoadjuvant therapy. |
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| Measure | Description | Time Frame |
|---|---|---|
| 3-year overall survival (OS) rate | The proportion of subjects in the intention-to-treat population who are alive at 3 years after randomization. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| 5-year overall survival (OS) rate | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic complete response rate | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yue He, M.D. | Contact | +8613501950200 | HEY1683@sh9hospital.org.cn | |
| Feng Liu, M.D. | Contact | +8618917797783 | nuanliu@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Ninth Peolple's Hospital | Shanghai | Shanghai Municipality | 200000 | China |
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Participants are randomized 1:1 to downgraded surgery (experimental) or standard surgery (control).
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Open-label study; no parties are masked.
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| Standard Surgery | Procedure | Surgical planning and resection will be conducted based on tumor boundaries assessed prior to neoadjuvant therapy. |
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| radiotherapy | 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. |
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| adjuvant immunotherapy | Drug | Postoperative adjuvant immunotherapy was administered in accordance with the initial treatment plan and clinical indications. |
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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 | 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 | 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 | 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 | 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 |
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 | 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 | 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 | 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 | Intraoperative blood loss volume | Intraoperative |
| Blood transfusion volume | Intraoperative blood transfusion volume | Intraoperative |
| Tracheostomy rate | 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 | 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 | 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 | 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 | Medical costs incurred during the hospitalization for surgery and during postoperative radiotherapy and chemotherapy. | Through study completion, an average of 5 years |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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