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

NCT ID: NCT06356012

Last Updated: 2025-02-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-02
• Study Completion Date: 2028-12-31

Brief 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.

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.

Conditions

HSIL, High-Grade Squamous Intraepithelial Lesions; Vaginal Microbiome; Biomarkers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imiquimod

Intervention Type: DRUG

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

Loop Electrosurgical Excision Procedure

Intervention Type: PROCEDURE

Active comparator group will be treated with LEEP.

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.

Group Type: ACTIVE_COMPARATOR

Loop Electrosurgical Excision Procedure

Intervention Type: PROCEDURE

Active comparator group will be treated with LEEP.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Imiquimod

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

Intervention Type: DRUG

Loop Electrosurgical Excision Procedure

Active comparator group will be treated with LEEP.

Intervention Type: PROCEDURE

Other Intervention Names

IXIUM; LEEP

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

Farmoquimica S.A.

INDUSTRY

Sponsor Role: collaborator

Hospital de Cancer de Barretos - Fundacao Pio XII

OTHER

Sponsor Role: collaborator

Barretos Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Barretos Cancer Hospital

Barretos, , Brazil

Site Status: RECRUITING

Countries

Brazil

Facility Contacts

Ricardo Reis, PhD

Role: primary

drricardoreis@gmail.com

+551733216600 ext. 7308

Other Identifiers

71163523.1.0000.5437

Identifier Type: -

Identifier Source: org_study_id