Topical Aldara (Imiquimod) for Oral Cancer

Study Overview
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Brief Summary
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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). To assess the preliminary efficacy of topical imiquimod in neoadjuvant setting in patients with early-stage oral squamous cell carcinoma as determined by best response rate (CR and PR). To assess local and systemic safety and tolerability by CTCAE v5 criteria. To explore the effect of imiquimod on the tumor immune microenvironment by performing quantitative multiplex immunofluorescence.

Detailed Description
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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 CD4+ (cluster of differentiation 4+) T-cell and macrophage will correlate with response to therapy.

Official Title
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Exploratory Clinical Trial of Topical Imiquimod 5% Cream as Window-of-opportunity Monotherapy for Early-stage Oral Cancer

Conditions
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Oral Cancer

Intervention / Treatment
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* Drug: Imiquimod 5% Cream,Top,Pkt,0.25Gm


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Topical Aldara<br>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,Top,Pkt,0.25Gm<br>* Imiquimod as a 5% cream is being used to treat several skin cancers, including malignant melanoma, basal cell carcinoma (BCC) and SCC26-28. 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | The primary endpoint is the overall response rate as defined as the best response (CR and PR), confirmed at 4 weeks of the start of study therapy, using RECIST v1.1 criteria neoadjuvant setting in patients with early-stage oral squamous cell carcinoma. | up to 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall rate of toxicity | The secondary endpoint is defined as safety and toxicity assessed using CTCAE v5.0 criteria. CTCAE v5 criteria. | up to 17 months | 
| Response Rate of topical imiquimod | We will estimate response rate to topical imiquimod using the exact 95% confidence interval based on the binomial distribution. microenvironment by performing quantitative multiplex immunofluorescence. | up to 17 months |