Clinical trial NCT03233412: Randomized Clinical Trial Evaluating the Efficacy of Topical Imiquimod in High Grade Cervical Intraepithelial Lesions
Official title: Ensaio clínico Randomizado Avaliando a eficácia do Tratamento tópico Com Imiquimode em lesões Intraepiteliais Cervicais de Alto Grau
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High Grade Intraepithelial Neoplasia
Cervix Cancer
Keywords: high grade cervical intraepithelial neoplasia
Immunomodulatory treatment
Lead sponsor: Barretos Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Farmoquimica S.A.
First posted: 2017-07-28
Enrollment: 90
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients between 25 and 50 years old with histological diagnosis of high-grade intraepithelial lesion, obtained through satisfactory colposcopy and without previous treatment, who will be selected in the preventive clinic of the Hospital de Cancer de Barretos-SP (HCB ). Eligible patients will be identified at the return visit, when they will come to the hospital to check the result of the examination. In this study the patients will be randomized into two groups: Group 1: Control, where standard treatment will be offered, which is the conization of the uterine cervix with loop electrosurgical excision procedure(LEEP); Group 2: experimental group, which will receive topical treatment in the uterine cervix with immunomodulator (Imiquimod), for a period of 12 weeks, with weekly applications (1x / week). 30 to 60 days after immunomodulatory treatment the patient will be submitted to standard treatment with cervical conization with LEEP.
Primary purpose: TREATMENT

Brief summary: Cervical cancer is one of the leading malignancies affecting women, with 311,000 deaths in 2018, most of them seen in underdeveloped countries. This neoplasm has a pre-invasive state, such as cervical intraepithelial neoplasia (CIN), which is caused by HPV (Human Papillomavirus) infection. The female organism most often is able to eliminate the virus, especially in young patients. However, when the infection becomes persistent, especially for subtypes 16 and 18, the risk of CIN developing an increased. Cytological screening programs can efficiently and wirelessly do this. As high-grade intraepithelial lesions (CIN 2/3) are as demonstrated by worse regression rate, only 13.3% at one year, and higher risk for progression to invasive cancer. As CIN 2/3 need treatment, and as more therapies as they are excisional, which theoretically are better, however, they may compromise the reproductive future of women who are unthreatened, increasing the risk of preterm labor, premature rupture of amniotic membranes, low weight Birth and perinatal mortality. This relationship aroused interest in seeking alternative therapies. Decrease antiviral activity directed against HPV, associated with a higher rate of elimination of the infection. Immediate, an agent that stimulates like dendritic cells to producer cytokines and activates epithelial T cells. Imiquimode, when used in vulvar neoplasias, has been shown to be effective, presenting satisfactory results without treatment of CIN 2/3 of the uterine cervix, requiring a better scientific compilation. Based on these data, this study aims to evaluate the efficacy of topical immunomodulatory treatment for high-grade cervical intraepithelial lesions.


Eligibility criteria: Inclusion Criteria:

* Women between the ages of 25 and 50 with histological diagnosis of CIN 2/3;
* Living 300 km or less from the city of Barretos-São Paulo / Brazil.

Exclusion Criteria:

* Suspected adenocarcinoma (in situ or invasive) or invading squamous cell carcinoma by colposcopy and/or citology;
* Being pregnant or breastfeeding;
* Women with some immunodeficiency or transplanted;
* Previous treatment history for CIN 2/3.

Primary outcomes:
measure: Efficacy of immunomodulatory treatment with Imiquimod in high grade intraepithelial lesions of the cervix compared to standard electrosurgical excision procedure (LEEP) treatment.
timeFrame: 30 months
Secondary outcomes:
measure: Local and systemic adverse events
timeFrame: 30 months
measure: Compare CIN 2 and CIN 3 for the difference in response to immunomodulatory treatment
timeFrame: 30 months
measure: Definition of the difference in cost from actual standard treatment compared to Imiquimod
timeFrame: 30 months
measure: Evaluation of recurrence of high grade cervical squamous intraepithelial lesion after 2 years of treatment.
timeFrame: 24 months
measure: Evaluation of reoperation rate after immunomodulatory treatment associated with standard treatment with LEEP compared to LEEP alone.
timeFrame: 24 months
measure: Clearance HPV
timeFrame: 30 months
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Barretos Cancer Hospital
Study officials:
affiliation: Barretos Cancer Hospital
name: Ricardo D Reis, PhD
role: STUDY_DIRECTOR
affiliation: Barretos Cancer Hospital
name: Bruno DO Fonseca, MD
role: PRINCIPAL_INVESTIGATOR
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