Clinical Trials /

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

NCT03196180

Description:

This 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.

Related Conditions:
  • High Grade Cervical Intraepithelial Neoplasia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia
  • Official Title: A Phase I Safety and Dose-Finding Trial of Alternate-Weekly, Self-Administered, Intravaginal Application of 5-Fluorouracil and Imiquimod for Treatment of High-Grade Cervical Intraepithelial Lesions

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01079
  • SECONDARY ID: NCI-2017-01079
  • SECONDARY ID: N01-CN-2012-00031
  • SECONDARY ID: UAZ2016-08-02
  • SECONDARY ID: UAZ2016-08-02
  • SECONDARY ID: N01CN00031
  • SECONDARY ID: P30CA023074
  • NCT ID: NCT03196180

Conditions

  • High Grade Cervical Intraepithelial Neoplasia
  • p16 Positive Neoplastic Cells Present

Interventions

DrugSynonymsArms
ImiquimodAldara, R 837, S 26308, Zyclara
Topical FluorouracilActino-Hermal, Arumel, Carac, Cytosafe, Efudex, Efurix, Fiverocil, Fluoroplex, Flurox, Timazin, Tolak

Purpose

This 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess safety and tolerability of self-administered weekly intravaginal topical
      fluorouracil (5-fluorouracil [5-FU]) and imiquimod used on alternating weeks for 16 weeks in
      women with biopsy confirmed high grade cervical intraepithelial lesions.

      SECONDARY OBJECTIVES:

      I. Describe the response to intravaginal 5-FU and imiquimod. II. Describe type-specific human
      papillomavirus (HPV) clearance after treatment with intravaginal 5-FU and imiquimod.

      III. Measure biomarkers of local immune activation.

      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.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Women with biopsy confirmed high grade cervical intraepithelial lesions (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

          -  Creatinine within normal institutional limits

          -  Urinalysis within normal 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; women of child-bearing potential and
             men 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

        Exclusion Criteria:

          -  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;
             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+, use of immunosuppressive
             medications or systemic steroids, organ transplant recipients)

          -  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 cervical intraepithelial neoplasia grade 3
                  (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

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection (other than human papilloma virus [HPV]), symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements
      
Maximum Eligible Age:45 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:The response and type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
Measure:Type specific human papillomavirus (HPV) clearance
Time Frame:At end of study visit (4-6 weeks after the last agent application)
Safety Issue:
Description:The response and type-specific HR-HPV clearance will be reported along with their 95% confidence intervals.
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

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