Neoadjuvant Imiquimod Immunotherapy for Oral Cancer

Early Phase 1

Completed

Conditions: Oral Squamous Cell Carcinoma

Interventions: Drug: Imiquimod 5% Cream

Registration Number: NCT04883645

Lead Sponsor: Medical University of South Carolina

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: Topical Aldara	Imiquimod 5% Cream	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With 50% Reduction in Tumor Cell Count and Major Pathologic Response	Following 28 days of treatment	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.

Secondary Outcome Measures