Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07369882 | Recruiting

• 1 other identifier: SYSKY-2025-990-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, randomized, controlled, exploratory clinical trial designed to evaluate the efficacy and safety of de-escalated surgery compared with standard surgery in patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who achieved a partial response (PR) or complete response (CR) after neoadjuvant immunochemotherapy. Eligible patients will be randomly assigned in a 1:1 ratio to either the de-escalated surgery group (experimental) or the standard surgery group (control). The de-escalated surgery group will undergo limited tumor resection and selective neck dissection based on clinical and imaging response, while preserving important anatomical structures and functions when feasible. The control group will receive standard surgical treatment following NCCN guidelines. All patients will be evaluated using RECIST 1.1 criteria for radiological response and will undergo enhanced CT or MRI at baseline, before the second cycle of neoadjuvant therapy, within one week before surgery, 30 days after surgery, and every 3 months thereafter until 2 years post-surgery, disease recurrence, death, or study completion. The study aims to assess whether de-escalated surgery can achieve similar oncologic outcomes while improving postoperative function and quality of life. The primary endpoints are disease-free survival (DFS), health-related quality of life (HRQoL), and 3- and 5-year overall survival rates (OS rate). A total of 60 patients will be enrolled over a 3-year period, with 30 in each group.

Conditions

Locally Advanced Head and Neck Squamous Cell Carcinoma

Keywords

head and neck squamous cell carcinoma; locally advanced; De-escalated Surgery; Neoadjuvant

Outcome Measures

Primary Outcomes (3)

• Disease-Free Survival

  The time from randomization (or from the start of treatment in single-arm trials) to disease recurrence or death from any cause, whichever occurs first, will be analyzed. The Kaplan-Meier method will be used to estimate survival curves, and between-group comparisons will be performed using the log-rank test.

  2 years

• Change in Health-Related Quality of Life (HRQoL) Assessed by EORTC QLQ-C30

  The EORTC QLQ-C30 is a validated, cancer-specific instrument developed by the European Organisation for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients. It contains 30 items measuring global health status, functional domains (physical, role, cognitive, emotional, and social), and symptom scales (fatigue, pain, nausea/vomiting, etc.). Each item is scored on a 4-point Likert scale (1 = Not at all to 4 = Very much), except for two global health items scored from 1 (Very poor) to 7 (Excellent). Higher scores on functional and global health scales indicate better outcomes, whereas higher scores on symptom scales indicate worse outcomes.

  Baseline (preoperative), 1 month after surgery, and at each follow-up visit (every 3 months up to 60 months).

• Change in Head and Neck Cancer-Specific Quality of Life Assessed by EORTC QLQ-H&N43

  The EORTC QLQ-H\&N43 is a supplementary module to the QLQ-C30 designed to assess head and neck cancer-specific symptoms and functions. It includes 43 items covering domains such as pain, swallowing, speech, eating, social contact, and sexuality. Each item is rated on a 4-point Likert scale (1 = Not at all to 4 = Very much). Higher scores on symptom scales indicate worse symptoms or problems.

  Baseline (preoperative), 1 month after surgery, and at each follow-up visit (every 3 months up to 60 months).

Secondary Outcomes (3)

• Major pathological response

  Perioperative

• overall survival rate

  3 years and 5 years.

• Safety Endpoints

  through study completion, an average of 1 year

Study Arms (2)

Experimental arm

EXPERIMENTAL

Surgical De-escalation After Neoadjuvant Therapy

Procedure: Surgical De-escalation After Neoadjuvant Therapy

Control arm

ACTIVE COMPARATOR

Radical surgery combined with radiotherapy or chemoradiotherapy

Procedure: Radical surgery combined with radiotherapy or chemoradiotherapy

Interventions

Surgical De-escalation After Neoadjuvant Therapy PROCEDURE

The experimental group will undergo a de-escalated surgical approach, defined as follows: 1. Primary tumor resection: The total diameter of the resection margins will be reduced by ≥30% compared with the pre-neoadjuvant therapy measurement. Resection will be performed with an additional 10-15 mm margin beyond the shrunken tumor boundary. 2. Functional preservation: When appropriate, important anatomical structures and functional components such as the submandibular gland, mandible, epiglottis, oral commissure, parotid duct, eyeball, and major nerves may be preserved after thorough evaluation. 3. De-escalated neck dissection: (1) Patients with clinically node-negative (cN0) neck status both before and after neoadjuvant immunotherapy will be exempted from neck dissection. (2) For midline-crossing lesions (e.g., tongue, hard palate, or soft palate), patients with contralateral clinically node-negative (cN0) neck status both before and after neoadjuvant immunotherapy will be exemp

Experimental arm

Radical surgery combined with radiotherapy or chemoradiotherapy PROCEDURE

Radical resection of the primary tumor and neck dissection will be performed according to the NCCN guidelines, followed by adjuvant radiotherapy or chemoradiotherapy based on the postoperative pathological features.

Control arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with stage III-IVa head and neck squamous cell carcinoma (HNSCC) according to the AJCC 8th edition TNM staging system, who have achieved a partial response (PR) or complete response (CR) after receiving neoadjuvant immunochemotherapy consisting of a PD-1 inhibitor in combination with nab-paclitaxel and carboplatin/cisplatin.
• No prior history of other malignant tumors.
• Aged between 18 and 75 years.
• Normal baseline (preoperative) clinical and laboratory findings:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without the use of granulocyte colony-stimulating factor (G-CSF) within the previous 14 days
• Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days
• Hemoglobin \> 9 g/dL without blood transfusion or erythropoietin use within the previous 14 days
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• \. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
• \. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min
• \. Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN
• \. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with TSH outside the normal range may be included if total T3 (or FT3) and FT4 are within normal limits
• \. Normal myocardial enzyme profile (minor laboratory abnormalities judged by the investigator to be clinically insignificant are acceptable)
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study treatment (Cycle 1, Day 1). If the urine test is indeterminate, a serum test must be performed. Non-childbearing females are defined as those who have been postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy.
• All subjects (male or female) with reproductive potential must agree to use highly effective contraception (annual failure rate \<1%) during treatment and for at least 120 days after the last dose of study drug, or 180 days after the last dose of chemotherapy.

You may not qualify if:

• Diagnosis of another malignant tumor, or the primary lesion at the time of neoadjuvant therapy was not oral cancer.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to treatment. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment.
• History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known history of human immunodeficiency virus (HIV) infection (i.e., positive HIV-1/2 antibody).
• Untreated active hepatitis B infection, defined as HBsAg positivity with HBV-DNA levels exceeding the upper limit of normal (ULN) at the study site laboratory. Subjects meeting the following criteria may be enrolled:
• a. HBV viral load \< 1000 copies/mL (200 IU/mL) prior to first dosing, provided antiviral therapy is administered throughout the study period to prevent viral reactivation
• b. Subjects who are anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV-DNA(-) do not require prophylactic antiviral therapy but must undergo close monitoring for viral reactivation.
• Active hepatitis C virus (HCV) infection, defined as positive HCV antibody with detectable HCV-RNA above the lower limit of detection.
• Pregnant or lactating women.
• Presence of severe or uncontrolled systemic diseases, including but not limited to:
• \. Cardiac disorders: severe arrhythmias (e.g., complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmia, or persistent atrial fibrillation), unstable angina, or congestive heart failure (NYHA class ≥ II)
• \. Vascular diseases: history of unstable angina, myocardial infarction, transient ischemic attack, or stroke within 6 months prior to enrollment
• \. Poorly controlled hypertension: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg
• \. Pulmonary diseases: noninfectious pneumonitis requiring corticosteroid treatment within 1 year before first dosing, or active interstitial lung disease
• \. Infectious diseases: active infections requiring systemic therapy, or severe uncontrolled infections

Sponsors & Collaborators

• Qunxing Li,MD: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Combined Modality Therapy; Drug Therapy

Study Officials

• Jinsong Li, MD, PhD

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liansheng Wang, PhD (Candidate)

CONTACT

+8613535330603; wanglsh25@mail2.sysu.edu.cn

Qunxing Li, MD, PhD

CONTACT

+86 183 2069 9771; liqx73@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: December 31, 2025
• First Posted: January 27, 2026
• Study Start: January 12, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): January 31, 2030
• Last Updated: January 27, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)