Neoadjuvant Imiquimod Immunotherapy for Oral Cancer

NCT04883645 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1036257R21CA252441-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Oral Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Safety of Imiquimod Therapy

  2 months

Other Outcomes (2)

• Changes in Immune Cell Count

  Following 28 days of treatment

• RFS Follow-up

  1 year

Study Arms (1)

Experimental: Topical Aldara

EXPERIMENTAL

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

Interventions

Imiquimod 5% Cream DRUG

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.

Also known as: Aldera

Experimental: Topical Aldara

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Yoon AJ, Carvajal RD, Graboyes EM, Kaczmar JM, Albergotti WG, Kejner AE, Troob SH, Philipone E, Anoma JS, Armeson KE, Hill EG, Richardson MS, Woods TR, Chera BS, Nourollah-Zadeh F, Lee BJ, Pandruvada S, Kourtidis A, Kingsley C, O'Quinn EC, Mills S, Jordan VC, Spencer M, Fails D, McKee TD, Zaidi M, Brisendine A, Horn S, Mehrotra S, Ogretmen B, Newman JG. Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma. Front Immunol. 2025 Jan 27;16:1530262. doi: 10.3389/fimmu.2025.1530262. eCollection 2025.

  PMID: 39931064 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Angela J. Yoon
• Organization: Medical University of South Carolina

yoona@musc.edu

8437924496

Study Officials

• Angela Yoon, DDS

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 12, 2021
• Study Start: April 28, 2022
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2024
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)