Clinical trial NCT06356012: Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients Treated with Imiquimod
Official title: Immunophenotyping, Microbiome, Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients with High-grade Cervical Intraepithelial Lesions Treated with Imiquimod
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: HSIL, High-Grade Squamous Intraepithelial Lesions
Vaginal Microbiome
Biomarkers
Lead sponsor: Barretos Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: Farmoquimica S.A.
name: Hospital de Cancer de Barretos - Fundacao Pio XII
First posted: 2024-04-10
Enrollment: 96
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of participants with histological regression of High-grade squamous intraepithelial lesion (HSIL)
timeFrame: 3 years
Secondary outcomes:
measure: Correlation between vaginal microbiome and immunological response
timeFrame: 3 years
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Barretos Cancer Hospital
Study officials:
References: