Oral Squamous Cell Carcinoma
Conditions
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.
Interventions
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.
Sponsors
National Cancer Institute (NCI)
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Safety of Imiquimod Therapy | 2 months | Defined as safe no life-threatening (Grade 4) adverse events assessed by CTCAE v5 criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Immune Cell Count | Following 28 days of treatment | 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). |
| RFS Follow-up | 1 year | One-year relapse-free survival (RFS) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imiquimod Treatment 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.
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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Imiquimod Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 65 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 16 |
| other Total, other adverse events | 14 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
Primary
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.
Time frame: Following 28 days of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Imiquimod | Number of Participants With 50% Reduction in Tumor Cell Count and Major Pathologic Response | Greater than 50% reduction and Major Pathologic Response | 9 Participants |
| Experimental: Imiquimod | Number of Participants With 50% Reduction in Tumor Cell Count and Major Pathologic Response | Less than 50% reduction and Partial Response | 6 Participants |
Secondary
Safety of Imiquimod Therapy
Defined as safe no life-threatening (Grade 4) adverse events assessed by CTCAE v5 criteria.
Time frame: 2 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Imiquimod | Safety of Imiquimod Therapy | Grade 4 AEs | 0 Participants |
| Experimental: Imiquimod | Safety of Imiquimod Therapy | No Grade 4 AEs | 15 Participants |
Other Pre-specified
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).
Time frame: Following 28 days of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Imiquimod | Changes in Immune Cell Count | Contribution of Increase in Functional Helper T cells in Reduction in Tumor | 0.54 Normalized cells/mm^2 |
| Experimental: Imiquimod | Changes in Immune Cell Count | Contribution of Increase in Activated Cytotoxic T cells in Tumor Reduction | 0.55 Normalized cells/mm^2 |
Other Pre-specified
RFS Follow-up
One-year relapse-free survival (RFS)
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Imiquimod | RFS Follow-up | One-year RFS | 13 Participants |
| Experimental: Imiquimod | RFS Follow-up | Recurrence within one-year | 1 Participants |