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

Barretos Cancer Hospital

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Imiquimod; Procedure: Loop Electrosurgical Excision Procedure

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06356012

71163523.1.0000.5437

Details and patient eligibility

About

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.

Full 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.

Enrollment: 96 estimated patients

Sex: Female

Ages: 25 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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96 participants in 3 patient groups

Imiquimod treatment plus Loop Electrosurgical Excision Procedure

Experimental group

Description:

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.

Treatment:

Procedure: Loop Electrosurgical Excision Procedure

Drug: Imiquimod

Loop Electrosurgical Excision Procedure

Active Comparator group

Description:

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.

Treatment:

Procedure: Loop Electrosurgical Excision Procedure

healthy population

No Intervention group

Description:

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.