Comparing smaller, targeted surgery versus standard surgery after pre-surgery immunotherapy for locally advanced head and neck cancer

Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Randomized, Single-center Exploratory Clinical Study

This trial tests whether smaller, response-guided surgery instead of the usual larger operation after neoadjuvant PD-1‑based chemoimmunotherapy works for people with resectable locally advanced head and neck squamous cell carcinoma who had a partial or complete response.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07369882 on ClinicalTrials.gov

What this trial studies

This single-center, open-label, randomized trial enrolls patients with resectable stage III–IVa head and neck squamous cell carcinoma who achieved a partial or complete radiologic response after neoadjuvant PD‑1 inhibitor combined with nab‑paclitaxel and carboplatin/cisplatin. Participants are randomized 1:1 to either de-escalated surgery — which reduces resection margins and selectively preserves anatomic structures and nodal levels based on imaging and clinical response — or to standard surgery per NCCN guidelines. Radiologic response is measured by RECIST 1.1 with contrast-enhanced CT or MRI and patients are followed for oncologic outcomes and functional preservation. The trial is exploratory and aims to determine if smaller operations can maintain cancer control while reducing surgical morbidity.

Who should consider this trial

Good fit: Ideal candidates are adults (18–75) with resectable stage III–IVa HNSCC who achieved a partial or complete response after neoadjuvant PD‑1‑based chemoimmunotherapy and who have adequate blood counts and organ function and no prior other malignancy.

Not a fit: Patients who did not achieve a partial or complete response, have unresectable or metastatic disease, or have poor organ function or other contraindications to surgery are unlikely to benefit from the de‑escalation approach tested here.

Why it matters

Potential benefit: If successful, this approach could allow patients to keep more swallowing, speech, and cosmetic function while still controlling their cancer.

How similar studies have performed: Prior de‑escalation efforts—particularly in HPV‑positive oropharyngeal cancer—and early neoadjuvant immunotherapy studies have shown promise for reducing treatment morbidity, but randomized de‑escalation after PD‑1‑based neoadjuvant chemoimmunotherapy remains exploratory.

Eligibility criteria

Inclusion Criteria:

* 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:
* 1.Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without the use of granulocyte colony-stimulating factor (G-CSF) within the previous 14 days
* 2.Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days
* 3.Hemoglobin \> 9 g/dL without blood transfusion or erythropoietin use within the previous 14 days
* 4.Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
* 5\. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
* 6\. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min
* 7\. Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN
* 8\. 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
* 9\. 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.
* Adverse events related to neoadjuvant therapy (e.g., bone marrow suppression, thyroiditis, hypothyroidism, hepatitis, nephritis, myocarditis, myositis, etc.) must have been adequately controlled and resolved to grade 0-2 before surgery. Patients assessed by anesthesiology as fit for general anesthesia may be included.
* Patients with pre-existing comorbidities prior to neoadjuvant therapy may also be enrolled if evaluated by anesthesiology and deemed able to tolerate general anesthesia.
* Signed written informed consent.

Exclusion Criteria:

* 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:
* 1\. 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)
* 2\. Vascular diseases: history of unstable angina, myocardial infarction, transient ischemic attack, or stroke within 6 months prior to enrollment
* 3\. Poorly controlled hypertension: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg
* 4\. Pulmonary diseases: noninfectious pneumonitis requiring corticosteroid treatment within 1 year before first dosing, or active interstitial lung disease
* 5\. Infectious diseases: active infections requiring systemic therapy, or severe uncontrolled infections
* 6\. Active pulmonary tuberculosis
* 7\. Gastrointestinal diseases: clinically active diverticulitis, intra-abdominal abscess, or intestinal obstruction
* 8\. Hepatic disorders: liver cirrhosis, decompensated liver disease, or acute/chronic active hepatitis
* 9\. Uncontrolled diabetes mellitus: fasting blood glucose (FBG) \> 10 mmol/L
* 10\. Renal dysfunction: urine protein ≥ ++ on routine urinalysis and 24-hour urinary protein \> 1.0 g
* 11\. Psychiatric disorders: severe mental illness that may affect treatment compliance.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jinsong Li, MD, PhD — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Liansheng Wang, PhD (Candidate)

Conditions Locally Advanced Head and Neck Squamous Cell Carcinoma; head and neck squamous cell carcinoma; locally advanced; De-escalated Surgery; Neoadjuvant