MOHs Surgery and Short-Course Radiation Therapy With Structured Follow-Up for Head & Neck Squamous Cell Skin Cancer

NCT06998342 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: UVMCC2410/STUDY00003513
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate if short-course radiation therapy (SCRT) can effectively treat high-risk cutaneous squamous cell carcinoma (cSCC) and if active surveillance is a safe alternative to radiation for moderate-risk cSCC in adults with head and neck cSCC who have undergone surgery. The main questions it aims to answer are: Does short-course radiation therapy (5 treatments over 2 weeks) effectively prevent cancer recurrence in high-risk patients? Can moderate-risk patients be safely monitored with active surveillance instead of receiving radiation? Researchers will compare: Short-course radiation therapy (SCRT) for high-risk patients to historical data on long-course radiation to determine effectiveness. Active surveillance for moderate-risk patients to expected recurrence rates to assess safety. Participants will: High-Risk Group (SCRT): Receive short-course radiation therapy and attend follow-up visits. Moderate-Risk Group (Active Surveillance): Have regular check-ups, including clinical exams and imaging, to monitor for cancer recurrence. Optionally provide blood samples for future biomarker research.

Conditions

Cutaneous Squamous Cell Carcinoma (CSCC)

Keywords

Cutaneous Squamous Cell Carcinoma; Head and Neck Cancer; Neoadjuvant Therapy; Immunotherapy; Surgical Oncology; Clinical Trial; Radiation

Outcome Measures

Primary Outcomes (1)

• Exploring the Efficacy of Adjuvant Hypofractionated Radiation Therapy in High-Risk cSCC Head and Neck Patients: A Comparison of 2-Year Locoregional Recurrence Rates

  To explore the potential efficacy of adjuvant hypofractionated radiation therapy (SCRT) in high-risk cutaneous squamous cell carcinoma (cSCC) head and neck patients by examining the 2-year locoregional recurrence rate (LRR) and comparing it to historical controls who received standard long-course radiation therapy (LCRT). Considering the variability in LRR among patients eligible for SCRT, the researchers aim to investigate whether a 2-year LRR \<25% could be achieved.

  2 years

Secondary Outcomes (18)

• 2-Year Locoregional Recurrence Rate (LRR) in Moderate-Risk SCC Patients

  2 years

• 2-Year Overall Survival (OS) in High-Risk SCC Patients Receiving SCRT

  2 years

• Health-Related Quality of Life (HRQoL) in High-Risk SCC Patients as Measured by EORTC QLQ-C30

  3 years

• 2-Year Overall Survival (OS) in Moderate-Risk SCC Patients

  2 years

• 2-Year Disease-Specific Survival (DSS) in Moderate-Risk SCC Patients

  2 years

Study Arms (2)

Moderate-Risk Cohort

EXPERIMENTAL

Patients meeting moderate-risk criteria will not receive adjuvant radiation therapy but will instead be monitored through regular clinical exams and imaging. This arm evaluates whether active surveillance is a safe alternative to radiation in this population by tracking recurrence rates and overall survival.

Other: Active Surveillance

High-Risk Cohort

EXPERIMENTAL

Patients classified as high risk will undergo SCRT, consisting of five fractions of radiation therapy over a two-week period. This approach aims to provide effective local control while minimizing treatment burden compared to conventional long-course radiation therapy (typically 30+ fractions over six weeks). The study will assess the efficacy, safety, and long-term outcomes of SCRT, including recurrence rates, toxicity profiles, and patient-reported quality of life.

Radiation: Short course radiation; Other: Active Surveillance

Interventions

Short course radiation RADIATION

The radiation arm in this study involves Short Course Radiation Therapy (SCRT), which consists of 5 fractions delivered twice a week (either Monday/Thursday or Tuesday/Friday).

High-Risk Cohort

Active Surveillance OTHER

The Active Surveillance arm (Group M) aims to monitor participants with moderate-risk cutaneous squamous cell carcinoma (cSCC) after surgical resection, without immediate intervention unless disease progression occurs. Participants will undergo regular clinical evaluations, physical exams, and skin checks to detect new lesions or signs of recurrence. Imaging, including ultrasound and CT/MRI scans, will be performed every 6 months for up to 3 years to monitor for metastasis or progression. Blood samples will be collected for future biomarker analysis to identify indicators of disease recurrence. Participants will also complete quality of life assessments using the EORTC QLQ-C30 and Skin Cancer Index (SCI) to evaluate the impact of surveillance on their daily lives. If disease progression is detected, radiation therapy may be initiated. The study will track overall survival without initiating radiation, as well as disease progression and quality of life outcomes, to determine if active s

High-Risk Cohort; Moderate-Risk Cohort

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed cutaneous squamous cell carcinoma of the head \& neck region, defined as extending from vertex of head to supraclavicular region.
• Mohs micrographic surgery with or without further surgery following Mohs to achieve negative margins (i.e. R0 margin status) within 70 days prior to registration
• Appropriate stage for study entry (T1-T3 N0 M0; AJCC 8th ed.) based on the following diagnostic workup:
• Clinical exam within 60 days prior to registration
• CT head \& neck/soft tissue with IV contrast within 60 days prior to registration or MR face and neck with IV contrast. IV contrast may be held if medically contraindicated.
• Bilateral neck ultrasound within 60 days prior to registration
• Risk Factors fitting either the High-Risk or Moderate-Risk Categories:
• Risk Factor Definitions
• Major Risk Factors: Microscopic Extensive PNI (defined as PNI for \>3 nerves with all involved nerves either \>0.1 mm in size and/or deeper than the dermis), Gross PNI (defined as perineural spread evidenced on by MRI imaging, with cranial nerve deficit, or both), Size \>6 cm, or Recurrent disease status post prior Mohs
• Moderate-Risk Factors: Poor differentiation, 4-6 cm, PNI (defined as \>0.1 mm in size)
• BWH Risk factors: \>2 cm, poor differentiation, deep invasion, PNI (\>0.1 mm in size)
• BWH: T2a = 1 risk factor; T2b = 2-3 risk factors, T3 = 4 risk factors
• High-Risk Group (Group H) Any 1 major OR 2-3 moderate OR BWH T3
• Moderate-Risk Group (Group M) BWH T2b not meeting criteria for High-Risk.

You may not qualify if:

• Patients receiving any other investigational agents.
• Patients pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Serious medical comorbidities that, in the opinion of the radiation oncologist, would prevent participation in this study.
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for different cancer(s) is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy.

Sponsors & Collaborators

• University of Vermont Medical Center: lead

Study Sites (1)

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Central Study Contacts

Christopher Anker, MD

CONTACT

(802) 656-2021; chris.anker@uvmhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist. Professor, Radiation-Oncology

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 31, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)