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RecruitingNCT06356012Updated Feb 5, 2025

Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients Treated with Imiquimod

A Phase 4 interventional study of Imiquimod and Loop Electrosurgical Excision Procedure in HSIL, High-Grade Squamous Intraepithelial Lesions, Vaginal Microbiome and Biomarkers, sponsored by Barretos Cancer Hospital. Recruiting at 1 site in Brazil. Open to female participants aged 25 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-05.

Sponsored by Barretos Cancer Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
96
Allocation
Randomized
Ages
25 Years to 45 Years
Sex
Female
01

Study summary

The goal of this clinical trial is to identify the immunophenotypic profile of the local immune response, the cervicovaginal microenvironment and the microbiological profile of women with CIN 3 treated with imiquimod. Participants will be divided in 3 groups: CIN 3 who will use 16 doses of imiquimod in the uterine cervix, applied twice a week and will be treated with LEEP procedure; 2) patients with CIN 3 who will undergo standard treatment with LEEP procedure; 3) patients with negative cytology and HPV (human papillomavirus) test. Blood and cervicovaginal lavage collections will be performed at different times, for comparisons between cellular response profiles to imiquimod during treatment and baseline levels in healthy patients.

Read the detailed description

INTRODUCTION: High-grade intraepithelial lesions (CIN 2/3) are considered precursor lesions of cervical cancer, and its treatment involves destructive or excisional methods. Some studies have proven the efficacy of the immunomodulator imiquimod as a topical treatment for CIN 2/3 lesions. Imiquimod activates the innate immune response through dendritic cells, monocytes and macrophages, in addition to modulating the response pattern of T lymphocytes. Thus, the characterization of the immune response in the treatment with imiquimod in lesions caused by oncogenic HPV, may benefit women in a way that it is possible to measure the response of each patient, improving the understanding of its mechanism of action, directly impacting the efficacy and adverse events. caused by the drug. OBJECTIVES: To identify the immunophenotypic profile of the local immune response, the cervicovaginal microenvironment and the microbiological profile of women with CIN 3 treated with imiquimod. MATERIALS AND METHODS: It will be included 90 patients, 60 with high-risk HPV, diagnosed with CIN 3 and 30 patients with negative cytology and HPV. Patients will be divided into 3 groups: 1) patients with CIN 3 who will use 16 doses of imiquimod in the uterine cervix, applied twice a week; 2) patients with CIN 3 who will undergo standard treatment with Transformation Zone Excision (EZT); 3) patients with negative cytology and HPV. Blood and cervicovaginal lavage will be collected for immunophenotypic analysis (flow cytometry), quantification of immunological mediators (Cytometric Bead Array) and evaluation of the microbiome (MiniION). The results obtained will be correlated with the clinical and pathological data of the patients.

02

Conditions studied

  • HSIL, High-Grade Squamous Intraepithelial Lesions
  • Vaginal Microbiome
  • Biomarkers
03

Who can participate

Ages eligible
25 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Patients between 25 and 45 years of age (reproductive age);
  • High-risk HPV carriers;
  • Residents less than 300 km from the city of Barretos-São Paulo;
  • With a histological diagnosis of high-grade cervical squamous intraepithelial lesion (CIN 3), obtained through colposcopy-guided biopsy performed at the Barretos Cancer Hospital (HCB);
  • Acceptance of the Informed Consent Form.

Exclusion criteria

Exclusion Criteria:

  • Suspicion of invasive squamous cell carcinoma or Adenocarcinoma (in situ or invasive) by colposcopy and/or cytology;
  • Pregnant or breastfeeding;
  • Immunodeficiency condition;
  • Previous treatment for high-grade cervical squamous intraepithelial lesion;
  • Who have been immunized for HPV;
  • Have used antibiotics in the last 30 days
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
96 participants (estimated)

Study arms

  • Experimental
    Imiquimod treatment plus Loop Electrosurgical Excision Procedure

    36 patients diagnosed with CIN 3 who will be undergone 16 applications of 5g imiquimod twice a week and then Loop Electrosurgical Excision Procedure will procedure (60 days). Pathological analysis will evaluate the lesion histologically after immunomodulatory treatment. The individual's immunological response will also be evaluated during applications and after surgical intervention.

    Drug: Imiquimod · Procedure: Loop Electrosurgical Excision Procedure

  • Active comparator
    Loop Electrosurgical Excision Procedure

    30 patients diagnosed with CIN 3 who will be undergone Loop Electrosurgical Excision Procedure (60 days). Pathological analysis will evaluate the lesion histologically after treatment (LEEP). The individual's immunological response will also be evaluated after surgical intervention.

    Procedure: Loop Electrosurgical Excision Procedure

  • No intervention
    healthy population

    Immunological markers will be evaluated in a healthy population that had negative screening tests for cervical lesions to compare to the population in the injury and intervention groups.

Interventions

  • DrugImiquimod

    Experimental group will be treated with 16 applications of imiquimod and subsequently LEEP.

    Also known as: IXIUM

  • ProcedureLoop Electrosurgical Excision Procedure

    Active comparator group will be treated with LEEP.

    Also known as: LEEP

05

What researchers measure

Primary outcomes

  1. Number of participants with histological regression of High-grade squamous intraepithelial lesion (HSIL)

    A satisfactory immunological response is expected after the application of the immunomodulator imiquimod twice a week for 8 weeks in patients with CIN 3, with the objective of histological regression of the high squamous intraepithelial lesion (HSIL), which will be confirmed histologically after performing the gold standard LEEP treatment, which will be made available to all patients with CIN 3 included in the study

    Time frame: 3 years

Secondary outcomes

  1. Correlation between vaginal microbiome and immunological response

    Analysis of the vaginal microbiota and its correlation with the immunological response to imiquimod in CIN 3 lesions

    Time frame: 3 years

06

Study locations

1 of 1 sites recruiting
  • Barretos Cancer Hospital
    Barretos, Brazil
    Recruiting
07

Registry details

Key details

Study ID
NCT06356012
Lead sponsor
Barretos Cancer Hospital
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo, Farmoquimica S.A., Hospital de Cancer de Barretos - Fundacao Pio XII
Responsible party
Sponsor
First posted
Apr 10, 2024
Start date
Apr 2, 2024
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
Feb 5, 2025

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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