Neoadjuvant Imiquimod Immunotherapy for Oral Cancer

Pilot Clinical Trial of Neoadjuvant Toll-like Receptor 7 Agonist (Imiquimod) Immunotherapy in Early-Stage Oral Squamous Cell Carcinoma

The purpose of this research study is to find out what effects, good and/or bad, topical application of the drug Aldara will have on patients and on their oral cancer. Aldara is a drug that activates toll-like receptor (TLR) in oral cancer cells causing self-destruction of tumor cells. It also activates immune cells to attack and eliminate cancer cells. Aldara is currently approved by the Food and Drug Administration (FDA) for treatment of skin cancer and melanoma. Its use in this study is 'off-label' (use of a drug approved by FDA for skin cancer to treat oral cancer in this study).

The preliminary efficacy of topical imiquimod in a neoadjuvant setting in patients with early-stage oral squamous cell carcinoma will be determined by a reduction in tumor cellularity in post-treatment tissue compared to pre-treatment tissue. Safety and tolerability will be evaluated by CTCAE v5 criteria. The effect of imiquimod on the tumor immune microenvironment will be assessed by performing quantitative multiplex immunofluorescence.

Study Overview

• Status: Completed
• Conditions: Oral Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Imiquimod 5% Cream

Detailed Description

The researchers propose an exploratory clinical trial to evaluate the efficacy of topical imiquimod, a TLR-7 agonist, in patients with early-stage oral squamous cell carcinoma. The analysis of pre- and post-treatment tumor specimen collected from patients treated on this study will be used for quantitative immunoflourescence analysis to assess the immunomodulatory activity of imiquimod in human tumor samples. The researchers hypothesize that TLR-7 stimulation will reduce the size of the tumor in patients with early-stage oral squamous cell carcinoma. The researchers anticipate that activation of immune cells will correlate with response to therapy.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previously untreated and biopsy confirmed oral squamous cell carcinoma (OSCC)
• Clinical (TNM) stage I or II
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) =< 2

Exclusion Criteria:

• Patients associated with prior therapy requiring treatment with systemic immunosuppressive treatments with the exception of vitiligo, childhood asthma that has resolved, residual endocrinopathies requiring replacement therapy, or psoriasis that does not require systemic treatment
• Treatment with any other investigational agents
• Requirement for immunosuppressive intraoral topical or systemic corticosteroids prior to the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• HIV positive patients on combination antiretroviral therapy
• Have evidence of any other significant oral mucosal condition, clinical disorder, physical examination finding, or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study
• Pregnant women are excluded from this study because imiquimod may have adverse effect on the fetus (FDA pregnancy risk category C). Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with imiquimod, breastfeeding should be discontinued if the mother is receiving study treatment
• Male patients unwilling or unable to comply with pregnancy prevention measures
• Subjects not receiving initial surgical treatment at Medical University of South Carolina (MUSC)

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: Experimental: Topical Aldara; All patients receive the same treatment (there is no "placebo" arm). Treatment will be self-administered by the patients on an outpatient basis. All patients with untreated and biopsy confirmed oral squamous cell carcinoma (OSCC) who meet the inclusion criteria.

Drug: Imiquimod 5% Cream; Imiquimod as a 5% cream is being used to treat several skin cancers, including malignant melanoma, basal cell carcinoma (BCC) and SCC. With respect to SCC treatment, it has been demonstrated that imiquimod stimulates tumor destruction by recruiting T cells (cells in the immune system) from blood and by inhibiting tonic anti-inflammatory signals within the tumor. The patient will be instructed to apply imiquimod cream, 7 nights a week for 4 weeks to the oral tumor at bedtime.; Other Names: Aldera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 50% Reduction in Tumor Cell Count and Major Pathologic Response	A minimum of 50% reduction in tumor cell count assessed by quantitative multiplex immunofluorescence (qmIF) within the tumor bed of the surgical tissue (post-treatment) compared to the biopsy tissue (pre-treatment). In addition, the major pathologic response to be assessed using Immune-Related Pathologic Response Criteria (irPCR) in the tumor bed of the post-treatment surgical tissue.	Following 28 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Imiquimod Therapy	Defined as safe no life-threatening (Grade 4) adverse events assessed by CTCAE v5 criteria.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Immune Cell Count	To assess the changes in anti-tumoral immune cell counts from pre- to post-therapy by quantitative multiplex immunofluorescence (normalized cell number per mm^2 from 6 to 8 regions of interest).	Following 28 days of treatment
RFS Follow-up	One-year relapse-free survival (RFS)	1 year

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Angela Yoon, DDS, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Toll-Like Receptor Agonists; Immunomodulating Agents; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: 103625; 7R21CA252441-02 (U.S. NIH Grant/Contract)

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