Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia

NCT03196180 | Completed Early Phase 1 Results DMC FDA Drug

• 6 other identifiers: NCI-2017-01079N01-CN-2012-000311712088061UAZ2016-08-02N01CN00031P30CA023074
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I clinical trial studies the side effects of topical fluorouracil and imiquimod ointment in treating patients with high-grade cervical intraepithelial neoplasia. Topical fluorouracil may kill precancerous cells. Imiquimod ointment may stimulate the immune system. Applying topical fluorouracil and imiquimod ointment may cause fewer side effects and may be a better way to treat patients with precancerous cervical lesions.

Conditions

Cervical Intraepithelial Neoplasia Grade 2/3; Cervical Squamous Cell Carcinoma In Situ; Cervical Squamous Intraepithelial Neoplasia 2; High Grade Cervical Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (1)

• Feasibility of Intravaginal Use 5-FU and Imiquimod on Alternating Weeks in Women With Biopsy Confirmed High Grade Cervical Squamous Intraepithelial Lesions.

  Feasibility is evaluated based on safety and tolerability of the study intervention. For safety, the study assessed the number of participants experiencing the specified adverse events defined as Grade 2 or greater toxicity (or Grade 1 toxicity of any genital lesion (blisters, ulcerations, or pustules)) that is possibly, probably, or definitely related and lasts for more than 5 days. For tolerability, the study assessed the number of participants who were not able to apply at least 50% of the treatment due to the specified adverse events.

  Up to 22 weeks

Secondary Outcomes (4)

• Response to Intravaginal 5-FU and Imiquimod Defined as Histologic Regression and Clearance of High-risk Human Papilloma Virus (HR-HPV)

  At end of study visit (4-6 weeks after the last agent application)

• Type Specific Human Papillomavirus (HPV) Clearance

  At end of study visit (4-6 weeks after the last agent application)

• Change in Expression of Biomarkers of Local Immune Activation (Cytokines) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod

  Baseline to up to end of study visit (4-6 weeks after last agent application)

• Change in Expression of Biomarkers of Local Immune Activation (Toll Like Receptors (TLRs)) After Treatment With Self-administered Intravaginal Topical Fluorouracil and Imiquimod

  Baseline to up to end of study visit (4-6 weeks after last agent application)

Study Arms (1)

Treatment (topical fluorouracil, imiquimod)

EXPERIMENTAL

Patients receive topical fluorouracil intravaginally via applicator at weeks 1, 3, 5, 7, 9, 11, 13, and 15 and imiquimod intravaginally via applicator at weeks 2, 4, 6, 8, 10, 12, 14, and 16. Patients who are menstruating will delay application until the end of the menstrual cycle.

Drug: Imiquimod; Drug: Topical Fluorouracil

Interventions

Imiquimod DRUG

Given intravaginally

Also known as: Aldara, R 837, S 26308, Zyclara

Treatment (topical fluorouracil, imiquimod)

Topical Fluorouracil DRUG

Given intravaginally

Also known as: Actino-Hermal, Arumel, Carac, Cytosafe, Efudex, Efurix, Fiverocil, Fluoroplex, Flurox, Timazin, Tolak

Treatment (topical fluorouracil, imiquimod)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women with biopsy confirmed high grade cervical squamous intraepithelial lesions (i.e., cervical squamous intraepithelial neoplasia 3 \[CIN3\] lesions, and cervical squamous epithelial neoplasia 2 \[CIN2\] lesions with diagnosis confirmed by positive p16 immunohistochemistry staining) within 12 weeks of baseline visit
• Karnofsky \>= 70%
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Platelets \>= 100,000/microliter
• Serum creatinine =\< the upper institutional limits
• Participants must have a negative human immunodeficiency virus (HIV) antibody/antigen test and negative Chlamydia (C.) trachomatis/Neisseria (N.) gonorrhea nucleic acid amplification test (NAAT)
• Agree to use an effective form of contraception; the effects of intravaginal 5-fluorocuracil and imiquimod on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because 5- fluorouracil is known to be teratogenic, women of child-bearing potential must agree to use adequate dual methods of contraception (hormonal method of birth control, intrauterine device, or tubal ligation - plus condoms) or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Women treated previously with 5-fluorouracil or imiquimod or other medications for high-grade squamous intraepithelial lesions will be excluded from the study
• Concurrent vaginal, vulvar, anal lesions or symptomatic infections
• Pregnant or planning pregnancy within the next 6 months, or breastfeeding; pregnant women are excluded from this study because 5-fluorouracil is an antimetabolite with the potential for teratogenic effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with 5-fluorouracil, breastfeeding should be discontinued if the mother is treated with 5-fluorouracil
• Inability to speak or read English or Spanish
• Prior hysterectomy
• Use of anticoagulant medications
• Subjects who have a known immunocompromised condition (HIV positive \[+\], use of immunosuppressive medications or systemic steroids, organ transplant recipients) or autoimmune conditions (e.g. psoriasis, rheumatoid arthritis or other known autoimmune conditions)
• Evidence of invasive anal, vulva, vaginal, or cervical carcinoma; prior loop electrosurgical excision procedure (LEEP) or ablative treatment within 6 months prior to study entry; other invasive malignancies, with the exception of non-melanoma skin cancer, within the last 5 years
• Pathologic findings consistent with
• Atypical endometrial cells or serious glandular-cell atypia (atypical glandular cells, favor neoplasia cytology diagnosis)
• Evidence of cervical carcinoma on Pap smear or biopsy
• More than two cervical quadrants of CIN 3 as visualized by colposcopy
• Nonvisual squamous columnar junction on colposcopy with no concurrent endocervical sampling performed
• Use of other investigational agents within 6 months prior to enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil or imiquimod

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Imiquimod; Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Sherry Chow, PhD
• Organization: University of Arizona

schow@azcc.arizona.edu

520-626-3358

Study Officials

• Lisa Rahangdale

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 22, 2017
• Study Start: October 15, 2019
• Primary Completion: November 4, 2020
• Study Completion: August 2, 2024
• Last Updated: April 8, 2025
• Results First Posted: February 23, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)