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

Biomarkers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06356012
• Other study ID #: 71163523.1.0000.5437
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 2, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2024
• Source: Barretos Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 25 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Biomarkers
• Carcinoma in Situ
• Carcinoma, Squamous Cell
• HSIL, High-Grade Squamous Intraepithelial Lesions
• Squamous Intraepithelial Lesions of the Cervix
• Vaginal Microbiome

Intervention

Drug:
• Imiquimod
Experimental group will be treated with 16 applications of imiquimod and subsequently LEEP.

Procedure:
• Loop Electrosurgical Excision Procedure
Active comparator group will be treated with LEEP.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Barretos Cancer Hospital	Farmoquimica S.A., Fundação de Amparo à Pesquisa do Estado de São Paulo, Hospital de Cancer de Barretos - Fundacao Pio XII

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	3 years
Primary	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	3 years
Secondary	Identification of immune response in vaginal and plasma collection	Detection of the immunological response measured from vaginal and plasma collection during applications of the immunomodulatory drug (pg/,L)	3 years