ctDNA in Cutaneous Squamous Cell Carcinoma

ctDNA Clearance and ctDNA Monitoring Study in Cutaneous Squamous Cell Carcinoma

The purpose of this study is to test the potential for a liquid biopsy assay to detect residual disease after surgery in patients with cutaneous squamous cell carcinoma as well as the potential for this assay to monitor response to immunotherapy treatment.

Study Overview

• Status: Recruiting
• Conditions: Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Diagnostic test: Blood and Tissue Collection

Detailed Description

The study aims to better understand whether circulating tumor DNA, or ctDNA, a type of personalized blood test informed by the tumor, can help monitor recurrence and treatment responses in patients with cutaneous squamous cell carcinoma (CSCC), especially during and after treatment. Blood samples will be collected during regular treatment visits or through mobile phlebotomy visits, and analyzed to study how ctDNA levels change over time. Participants will be in the study for 2 years.

Circulating tumor DNA consists of small fragments of DNA shed into the bloodstream by cancer cells. It may serve as a non-invasive biomarker for detecting and monitoring CSCC, offering insights into tumor treatment response and/or progression. ctDNA can provide a "liquid biopsy," allowing real-time tracking of tumor dynamics. Specifically, the study is researching how ctDNA levels change in patients undergoing surgery, immunotherapy, or other standard treatments. The goal is to see if ctDNA can serve as a biomarker to better understand treatment response and detect potential progression/ recurrence of the cancer.

This study does not involve any experimental drugs or devices. All drugs and treatments administered to participants, including surgery and immunotherapy, are part of standard of care. The ctDNA blood test is being used as a research tool and is not currently approved by the U.S. Food and Drug Administration (FDA) for monitoring CSCC. The study aims to evaluate its potential future use as a reliable biomarker.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Michael Cheung, MSc, CCRP; Phone Number: 6175736060; Email: mcheung0@meei.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts Eye and Ear
      • Contact: Michael Cheung, MSc, CCRP; Phone Number: 617-573-6060; Email: mcheung0@meei.harvard.edu
      • Principal Investigator: Sophia Shalhout, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients ages 18 and older, who have been diagnosed with cutaneous squamous cell carcinoma (CSCC)

Description

Post-Operative Cohort

Inclusion Criteria:

• Patients with surgically resectable primary CSCC with PNI (>0.1mm caliber nerve) or at least 2 high-risk features defined as size > 2cm, recurrent CSCC, LVI, immunosuppressed, poorly differentiated, and/or invasion >6mm/beyond subcutaneous fat;
• Patients with surgically resectable regional metastases not receiving neoadjuvant therapy

Exclusion Criteria:

• Patients with Cutaneous Squamous Cell Carcinoma not amenable to surgical resection
• Patients receiving or undergoing systemic therapies.

Neoadjuvant Cohort

Inclusion Criteria:

• Patients with resectable AJCC (8th ed) Stage II, III or IV(M0) CSCC treated with neoadjuvant immunotherapy as part of standard care.

Exclusion Criteria:

• Patients ineligible for neoadjuvant treatment.

Definitive Immunotherapy Cohort

Inclusion Criteria:

• Patients with unresectable locally advanced or metastatic CSCC, AJCC (8th ed) Stage II, III, or IV), receiving immunotherapy as part of standard of care.

Exclusion Criteria:

• Patients undergoing systemic therapies outside the standard of care or enrolled in conflicting clinical trials.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Post-Operative Cohort; Cutaneous Squamous Cell Carcinoma cancer patients treated with surgery.	Diagnostic test: Blood and Tissue Collection; Blood samples, and tissue samples will be collected from the participants, and used to determine whether circulating tumor DNA (ctDNA) testing can help monitor treatment in patients with CSCC, and to determine how ctDNA levels change in patients.; Other Names: ctDNA test
Neoadjuvant Cohort; Cutaneous Squamous Cell Carcinoma patients treated with Neoadjuvant immunotherapy.	Diagnostic test: Blood and Tissue Collection; Blood samples, and tissue samples will be collected from the participants, and used to determine whether circulating tumor DNA (ctDNA) testing can help monitor treatment in patients with CSCC, and to determine how ctDNA levels change in patients.; Other Names: ctDNA test
Definitive Immunotherapy Cohort; Cutaneous Squamous Cell Carcinoma patients treated with definitive immunotherapy.	Diagnostic test: Blood and Tissue Collection; Blood samples, and tissue samples will be collected from the participants, and used to determine whether circulating tumor DNA (ctDNA) testing can help monitor treatment in patients with CSCC, and to determine how ctDNA levels change in patients.; Other Names: ctDNA test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year recurrence-free survival (RFS) in patients with detectable vs no detectable ctDNA after surgery	To determine if there is an association between ctDNA clearance (defined as no detection of ctDNA) after surgical intervention and 2-year recurrence-free survival (RFS). The outcome will measure both ctDNA clearance (as a binary variable: detection or no detection) and RFS (measured in months). The association between these two outcomes will be analyzed as the primary outcome to determine if no detection of ctDNA is associated with longer RFS.	24 Months
Neoadjuvant Cohort Primary Outcome: Response Monitoring	To evaluate ctDNA as a biomarker of response to neoadjuvant immunotherapy.	24 Months
Definitive Treatment Cohort Primary Outcome	To evaluate whether ctDNA correlates with response to immunotherapy.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Operative Cohort Secondary Outcome: Residual Free Survival (RFS) Surveillance over 2 Year	To evaluate RFS during the surveillance period, stratified by ctDNA test status over time to determine if ctDNA levels predict recurrence	24 Months
Neoadjuvant Cohort Secondary Outcome: Correlation with Pathological Response	To evaluate if ctDNA correlates with pathological response to neoadjuvant therapy. This will help determine if ctDNA may one day be used to help risk stratify which patients need surgery after neoadjuvant immunotherapy.	24 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome	To evaluate the time to ctDNA clearance (defined as the time from surgical intervention to the point where ctDNA is no longer detected, if ever) in the postoperative period, defined as months since surgery.	24 Months

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: Massachusetts General Hospital; Haystack Oncology, Inc.
• Investigators: Principal Investigator: Sophia Z. Shalhout, PhD, Massachusetts Eye and Ear

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 13, 2025

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Skin cancer; Minimal Residual Disease (MRD); Liquid Biopsy; ctDNA; Circulating Tumor DNA; Advanced Skin Cancer; CSCC
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm, Residual; Skin Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 2024P003225

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No