Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia
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|ClinicalTrials.gov Identifier: NCT03196180|
Recruitment Status : Recruiting
First Posted : June 22, 2017
Last Update Posted : October 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cervical Intraepithelial Neoplasia Grade 2/3 Cervical Squamous Cell Carcinoma In Situ Cervical Squamous Intraepithelial Neoplasia 2 High Grade Cervical Intraepithelial Neoplasia||Drug: Imiquimod Other: Laboratory Biomarker Analysis Drug: Topical Fluorouracil||Phase 1|
I. Assess feasibility of a combination agent intervention (once-weekly self-administered intravaginal application of 5-fluorouracil alternating with once-weekly provider-applied imiquimod) for treatment of high-grade cervical squamous intraepithelial lesions.
I. Assess efficacy of the combination agent intervention on cervical disease regression (endpoint based on histologic regression from high-grade lesions to low-grade or no lesions and clearance of high risk-human papillomavirus [HPV] detection) between baseline and study exit visits.
II. Assess efficacy of the combination agent intervention on genotype-specific HPV clearance between baseline and study exit visits.
III. Assess efficacy of the combination agent intervention on biomarkers of local immune activation (measurement of changes in expression of Toll-like receptors (TLR) and T-regulatory cells and the levels of innate, immune mediating and proinflammatory cytokines with intravaginal 5-fluorouracil [FU] and imiquimod) between baseline and study exit visits.
OUTLINE: This is a phase I, dose escalation study of imiquimod.
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.
After completion of study treatment, patients are followed up within 8 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Feasibility Trial of Alternating Intravaginal Application of 5-Fluorouracil and Imiquimod for Treatment of High-Grade Cervical Squamous Intraepithelial Lesions|
|Actual Study Start Date :||September 30, 2019|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||August 31, 2020|
- Drug: Imiquimod
Given intravaginallyOther Names:
- R 837
- S 26308
- Other: Laboratory Biomarker Analysis
- Drug: Topical Fluorouracil
Given intravaginallyOther Names:
- Incidence of adverse events as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 16 weeks ]Will assess the number of participants experiencing the dose limiting toxicity (DLT). DLT is defined as grade 2 or greater toxicity (or grade 1 toxicity of any genital lesion [blisters, ulcerations, or pustule]) that is possibly, probably, or definitely related and lasts for more than 5 days. Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals. The adverse event rate and tolerability rate will be reported along with their 95% confidence intervals.
- Response to intravaginal 5-FU and imiquimod defined as histologic regression and clearance of high-risk human papilloma virus (HR-HPV) [ Time Frame: At end of study visit (4-6 weeks after the last agent application) ]The response and type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
- Type specific human papillomavirus (HPV) clearance [ Time Frame: At end of study visit (4-6 weeks after the last agent application) ]The overall response and type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
- Change in expression of biomarkers of local immune activation after treatment with self-administered intravaginal topical fluorouracil and imiquimod [ Time Frame: Baseline to up to end of study visit (4-6 weeks after last agent application) ]For each biomarker, the mean change and the associated standard deviation will be reported. Will measure the TLR (TLR2, TLR 3, TLR7, TLR8 and TLR9) and T-regulatory cell (Foxp3) mRNA expression and the innate (IFN-alpha2), immune mediating (IFN-gamma, IL-10, IL-12), and pro-inflammatory (IL-1alpha, -1beta, -6, -8, MIP-1alpha, TNF) cytokine.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03196180
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Lisa Rahangdale 919-843-7851 email@example.com|
|Principal Investigator: Lisa Rahangdale|
|Principal Investigator:||Lisa Rahangdale||The University of Arizona Medical Center-University Campus|