Recruiting
Phase 2

SCRT & Active Surveillance

Sponsor:

University of Vermont Medical Center

Code:

NCT06998342

Conditions

Cutaneous Squamous Cell Carcinoma (CSCC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Short course radiation

Active Surveillance

Study Details

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)

Study ID

NCT06998342

Start date

Jun 4, 2025

Status verified date

May, 2026

Completion date

May, 2031

Anticipated

Primary completion date

Apr, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

24 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Moderate-Risk Cohort

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.

experimental: High-Risk Cohort

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.

Interventions

Short course 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).

Active Surveillance

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

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Christopher Anker, MD

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

Locations

University of Vermont Medical Center

Recruiting

Burlington, Vermont, United States, 05401

Contacts

Christopher Anker, MD

7739804380chris.anker@uvmhealth.org

Ben Briggs, QA Officer

(802) 656-2021benjamin.briggs@uvmhealth.org

Principal Investigator:

Christopher Anker, MD

More Information

Sponsor

University of Vermont Medical Center

Last update posted

May 26, 2026

Last verified

May, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Vermont Medical Center on 2026-05-26.