A Phase 0 Window of Opportunity Trial of Intratumoral Seasonal Influenza Immunization in Cutaneous Squamous Cell Carcinoma (CSCC) Patients Awaiting Curative Excision

This study is investigating the effects on immune cells of injecting the influenza vaccine (also known as "flu shot") into cutaneous squamous cell carcinoma (CSCC) tumors prior to having standard-of-care Mohs excision surgery. The study will help understand if the addition of the influenza vaccine could improve the immune system response against the cancer.

The names of the study drug involved in this study is:

-Fluzone Influenza vaccine (flu shot)

Study Overview

• Status: Recruiting
• Conditions: Skin Cancer; Cutaneous Squamous Cell Cancer; Cutaneous Squamous Cell Carcinoma (CSCC)
• Intervention / Treatment: Biological: Fluzone Trivalent

Detailed Description

This Phase 0, window-of-opportunity study is investigating the effects on immune cells of injecting the influenza vaccine (also known as "flu shot") into cutaneous squamous cell carcinoma (CSCC) tumors prior to having standard-of-care Mohs excision surgery. This study will help understand if the addition of the influenza vaccine can improve the immune system response against the cancer.

The research study procedures include screening for eligibility, in-clinic visits, blood tests, and measurements and photographs of tumors.

It is expected that 25 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Karam Khaddour, MD; Phone Number: 617-632-6571; Email: karam_khaddour@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Karam Khaddour, MD; Phone Number: 617-632-6571; Email: karam_khaddour@dfci.harvard.edu
      • Principal Investigator: Karam Khaddour, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Karam Khaddour, MD; Phone Number: 617-632-6571; Email: karam_khaddour@dfci.harvard.edu
      • Principal Investigator: Karam Khaddour, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have a diagnosis of cutaneous squamous cell carcinoma that has been biopsied and confirmed histologically. Mixed histology (such as basosquamous carcinoma, sarcomatous carcinoma) is allowed.
• Participants must have a skin tumor that measures 10 - 39 mm (not less than 10 mm and not more than 39 mm) in longest dimension by clinical exam. (Participants may have more than one untreated CSCC at the time of enrollment, but only one CSCC may be treated with the study agent.)
• Participants must be candidates for treatment (excision) by Mohs micrographic surgery.
• Age ≥18 years. Because CSCC is exceptionally rare in patients <18 years of age, children are excluded from this study.
• ECOG performance status ≤3 (Karnofsky ≥40%, see Appendix A).
• Ability to understand and the willingness to sign a written informed consent document.
• For participants with a past medical history of Human immunodeficiency virus (HIV), they must be on effective anti-retroviral therapy with undetectable viral load measured within the 6 months prior to enrollment.
• For participants with a past medical history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• For participants with a past medical history of hepatitis C virus (HCV) infection, they must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Exclusion Criteria:

• CSCC with the following high-risk features including peri-neural invasion of >0.1 mm caliber, and invasion of tissue beyond the subcutaneous fat, and a diameter > 3.9 cm.
• Evidence of in-transit/satellite, nodal, or distant metastases from CSCC, in the present or in the past medical history, including evidence from physical exam of primary site and draining lymph node basin.
• History of solid organ transplant or allogeneic bone marrow transplant.
• History of allergic reactions attributed to the seasonal flu vaccine.
• History of Guillain-Barré syndrome.
• Participants with any uncontrolled intercurrent illness, including uncontrolled cardiac disease (New York Heart Association Class III or IV heart failure, myocardial infarction in the 6 months prior to enrollment, unstable angina).
• Participants who are receiving any other investigational agents for treatment of cancer.
• Participants with a past medical history of another malignancy whose natural history or treatment is likely to interfere with the safety or efficacy assessment of the investigational regimen, according to the treating investigator.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of intratumoral flu vaccine administration. Patients who do not agree to comply with these precautions are ineligible.
• Pregnant or nursing (breast-feeding) women are excluded from this study because there is an unknown but potential risk to multiple injections of flu vaccine in pregnant or nursing women.
• Note: Previous treatment with flu vaccination is not an exclusion criterion. Routine intramuscular seasonal influenza vaccination is not required nor prohibited.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluzone Vaccine in Cutaneous Squamous Cell Carcinoma; Enrolled participants will complete: Baseline visit; Days 1 and 8: Flu shot injection once; Day 15: Standard-of-care Mohs excision surgery and tissue collection.; Day 21 follow up visit with suture removal.; Day 38 follow up visit	Biological: Fluzone Trivalent; Inactivated influenza vaccine, 0.5mL single-dose, pre-filled syringe, via intratumoral (into a tumor) injection per protocol.; Other Names: Flu shot; Influenza Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change of CD8+ T-cells Density	CD8+ T-cell infiltration density (as measured by cells/mm2) on tumors is collected at the time of Mohs micrographic surgery compared to baseline (time of diagnostic biopsy).	Up to 15 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tumor Diameter	Evaluate the change in tumor diameter based on day 1 screening and the biopsy from the time of diagnosis.	Up to 15 Days
Adverse Events	Adverse events rate is defined as the percentage of participants who have experienced adverse events based on CTCAE 5.0	Up to 38 days
Mean Percent Change of Tumor Microenvironment Markers Compared Before and After Intratumoral Influenza Vaccination	Evaluation of the differences of effect on the mean percent change of tumor microenvironment markers before and after the administration of intratumoral influenza vaccine in CSCC lesions	Up to 15 Days

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Karam Khaddour, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: October 27, 2024
• First Submitted That Met QC Criteria: October 27, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Skin Cancer; Cutaneous Squamous Cell Carcinoma; Cutaneous Squamous Cell Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Skin Neoplasms; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines
• Other Study ID Numbers: 24-491

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes