Phase 2 Pragmatic Trial of Sentinel Lymph Node Biopsy (SLNB) in Patients With Clinically Node-Negative (cN0), High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) of the Head and Neck

Phase 2

Not yet recruiting

• Conditions: Cutaneous Squamous Cell Carcinoma of the Head and Neck
• Interventions: Procedure: Sentinel lymph node biopsy (SLNB); Procedure: Lymphadenectomy; Drug: Adjuvant Definitive Therapy

• Registration Number: NCT06990737
• Lead Sponsor: University of California, Davis

Brief Summary

This is a phase 2 pragmatic study at a single site that evaluates the clinical benefit of SLNB in patients with high-risk cSCC and cN0. The primary goal is to evaluate the efficacy of SLNB based on the DFS rate at 2 years post-definitive therapy.

Detailed Description

This is a phase 2 pragmatic study at a single site that evaluates the clinical benefit of SLNB in patients with high-risk cSCC and cN0. Participants must be a candidate for surgical intervention with sentinel lymph node biopsy (SLNB) and potential lymphadenectomy for treatment of cSCC. Following enrollment, participants will have preoperative lymphoscintigraphy performed before planned surgery. During surgery, participants will have SLNs excised from the affected area(s) per standard of care. Surgeon preference will dictate the order of the surgery for resecting the primary tumor. The surgeon may elect to return to the operating room for re-resection of the primary tumor to achieve a negative pathological margin. This may also coincide with a lymphadenectomy if the patient has a positive SLN. Participants will be monitored for adverse events (AEs) during and following their SLNB per institutional practices; only pre-specified AEs of interest will be documented for the study. Definitive systemic therapy (e.g., radiation therapy, chemoradiation therapy) will then be administered per standard of care following surgery.

The primary aim is to evaluate the efficacy of SLNB based on the disease-free survival (DFS) rate at 2 years post-definitive therapy compared to historical control. The patients' 2-year DFS will be analyzed using the Kaplan-Meier approach, and a one-sided log-rank test will be conducted to compare the DFS based on the historical control (50%). Secondary aims include surgical and perioperative morbidity evaluations, and efficacy evaluations assessed by 2-year local/regional control rate, 2-year overall survival, and sensitivity/ specificity of for occult nodal disease.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-16
• Study First Submitted QC: 2025-05-16
• Last Update Submitted: 2025-05-16
• Study Start: 2025-05-25
• Study First Posted: 2025-05-25
• Last Update Posted: 2025-05-25
• Primary Completion: 2031-07-01
• Study Completion: 2032-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Must have histologically and/or biochemically confirmed head and neck cSCC

2. Must have head and neck cSCC categorized as high risk:

   1. Location in the ear or the lip,
   2. Diameter greater than 2 cm,
   3. Depth greater than 4 mm,
   4. Perineural invasion,
   5. Poorly differentiated, and/or
   6. Recurrent disease

3. Lymph-node negative (cN0) status confirmed by computed tomography (CT) imaging.

4. Candidate for surgical intervention with sentinel lymph node biopsy (SLNB) and potential lymphadenectomy for treatment of cSCC.

5. Zubrod Performance Status 0-2

6. Age ≥18 years at time of consent.

7. Provision of signed and dated informed consent form.

8. Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria

1. Other active cancers.
2. Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease.
3. Prior non-head and neck invasive malignancy (except non-melanomatous skin cancer, including effectively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix) unless disease free for ≥ 2 years.
4. Diagnosis of head and neck mucosal SCC.
5. Prior systemic chemotherapy for head and neck mucosal SCC; note that prior chemotherapy for a different cancer is allowable.
6. Prior radiotherapy to the head and neck that would result in overlap of radiation therapy fields.
7. Patient with severe, active co-morbidity that would preclude a lymphadenectomy.
8. Pregnant or breast-feeding persons.
9. Prior surgery involving the lateral neck, including neck dissection or gross injury to the neck that would preclude surgical dissection for this trial. Prior thyroid and central neck surgery is permissible; biopsy is permitted. Prior surgery for confirmation of tumor pathology is permitted. Note: Borderline suspicious nodes that are ≥1 cm with radiographic finding suggestive of NOT malignant should be biopsied using U/S-guided fine-needle aspirate (FNA) biopsy.
10. Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia) or other active disease capable of causing lymphadenopathy (sarcoidosis or untreated mycobacterial infection).
11. Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte, or immunomodulatory therapy.
12. Currently participating in another investigational therapeutic trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sentinel lymph node biopsy (SLNB) + Lymphadenectomy + Adjuvant Definitive Therapy	Sentinel lymph node biopsy (SLNB)	Participants will have SLNs excised from the affected area(s) per standard of care. Surgeon preference will dictate the order of the surgery for resecting the primary tumor. This may also coincide with a lymphadenectomy if the patient has a positive SLN. Definitive systemic therapy (e.g., radiation therapy, chemoradiation therapy) will then be administered per standard of care following surgery.
Sentinel lymph node biopsy (SLNB) + Lymphadenectomy + Adjuvant Definitive Therapy	Lymphadenectomy	Participants will have SLNs excised from the affected area(s) per standard of care. Surgeon preference will dictate the order of the surgery for resecting the primary tumor. This may also coincide with a lymphadenectomy if the patient has a positive SLN. Definitive systemic therapy (e.g., radiation therapy, chemoradiation therapy) will then be administered per standard of care following surgery.
Sentinel lymph node biopsy (SLNB) + Lymphadenectomy + Adjuvant Definitive Therapy	Adjuvant Definitive Therapy	Participants will have SLNs excised from the affected area(s) per standard of care. Surgeon preference will dictate the order of the surgery for resecting the primary tumor. This may also coincide with a lymphadenectomy if the patient has a positive SLN. Definitive systemic therapy (e.g., radiation therapy, chemoradiation therapy) will then be administered per standard of care following surgery.

Primary Outcome Measures

Name	Time	Method
Disease-free survival (DFS)	Up to 2 years post definitive therapy completion	Defined as the time from definitive therapy to local/regional relapse, distant metastasis, or death due to any cause, whichever comes first.

Secondary Outcome Measures

Name	Time	Method
Local/regional control	Up to 2 years post definitive therapy completion	Defined as the time of completing definitive therapy to any evidence of disease in the primary or regional lymph nodes based on biopsy testing or imaging.
Overall survival	Up to 2 years post definitive therapy completion
Sensitivity of sentinel lymph node biopsy for occult nodal disease	Up to 14 days post-SLNB
Specificity of sentinel lymph node biopsy for occult nodal disease	Up to 14-days post-SLNB
Number of participants experiencing surgical and perioperative morbidity	Through 30 days post-sentinel lymph node biopsy	Assessed per the Clavien-Dindo Classification (CDC) scale 1 and a list of pre-specified complications

Trial Locations

Locations (1)

University of California, Davis; 🇺🇸 Sacramento, California, United States