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

February 3, 2025 updated by: Barretos Cancer Hospital

Immunophenotyping, Microbiome, Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients with High-grade Cervical Intraepithelial Lesions Treated with Imiquimod

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

96

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Barretos, Brazil
        • Recruiting
        • Barretos Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Experimental group will be treated with 16 applications of imiquimod and subsequently LEEP.
Other Names:
  • IXIUM
Procedure: Loop Electrosurgical Excision Procedure
Active comparator group will be treated with LEEP.
Other Names:
  • LEEP
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
Active comparator group will be treated with LEEP.
Other Names:
  • LEEP
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with histological regression of High-grade squamous intraepithelial lesion (HSIL)
Time Frame: 3 years
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
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between vaginal microbiome and immunological response
Time Frame: 3 years
Analysis of the vaginal microbiota and its correlation with the immunological response to imiquimod in CIN 3 lesions
3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between vaginal microbiome and immunological response
Time Frame: 3 years
Analysis of the vaginal microbiota and its correlation with the immunological response to imiquimod in CIN 3 lesions
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

March 4, 2024

First Submitted That Met QC Criteria

April 2, 2024

First Posted (Actual)

April 10, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 3, 2025

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 71163523.1.0000.5437

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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