HSIL, High-Grade Squamous Intraepithelial LesionsPhase 4NCT06356012
Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients Treated with Imiquimod
A Phase 4 study testing Imiquimod and Loop Electrosurgical Excision Procedure in people with HSIL, High-Grade Squamous Intraepithelial Lesions and Vaginal Microbiome, run by Barretos Cancer Hospital at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 25 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HSIL, High-Grade Squamous Intraepithelial Lesions, Vaginal Microbiome, Biomarkers
- What is being tested?
- Imiquimod and Loop Electrosurgical Excision Procedure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteBrazil
- Study dates
- 2 Apr 2024to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Barretos Cancer Hospital
Barretos
Ricardo Reis, PhD, +551733216600 ext. 7308, drricardoreis@gmail.com
About this study
Official title: Immunophenotyping, Microbiome, Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients with High-grade Cervical Intraepithelial Lesions Treated with Imiquimod
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.
Read the 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.
- Being tested
- Imiquimod, Loop Electrosurgical Excision Procedure
- Medical subject headings
- Squamous Intraepithelial Lesions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImiquimodDrug
Also called IXIUM
Experimental group will be treated with 16 applications of imiquimod and subsequently LEEP.
Loop Electrosurgical Excision ProcedureProcedure or surgery
Also called LEEP
Active comparator group will be treated with LEEP.
| Study group | Role | What they receive |
|---|---|---|
| Imiquimod treatment plus Loop Electrosurgical Excision Procedure | Experimental | 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. Receives: Drug: Imiquimod; Procedure: Loop Electrosurgical Excision Procedure |
| Loop Electrosurgical Excision Procedure | Active comparator | 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. Receives: Procedure: Loop Electrosurgical Excision Procedure |
| healthy population | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 years
Secondary outcomes (1)
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start2 Apr 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HSIL, High-Grade Squamous Intraepithelial LesionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Barretos Cancer Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo, Farmoquimica S.A., Hospital de Cancer de Barretos - Fundacao Pio XII
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06356012
- Sponsor's protocol ID
- 71163523.1.0000.5437
- Status last verified
- Apr 2024
- First submitted
- 4 Mar 2024
- Last updated
- 5 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunophenotyping, Microbiome, Clinical Outcome and Biomarkers for Predicting Immunological Response in Patients with High-grade Cervical Intraepithelial Lesions Treated with Imiquimod
- ClinicalTrials.gov ID
- NCT06356012
- Acronym / sponsor ID
- 71163523.1.0000.5437
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Barretos Cancer HospitalUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo, Farmoquimica S.A., Hospital de Cancer de Barretos - Fundacao Pio XII
- Study start
- 2 Apr 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 10 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Imiquimod treatment plus Loop Electrosurgical Excision Procedure | Experimental | Drug: Imiquimod, Procedure: Loop Electrosurgical Excision Procedure36 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. |
| Loop Electrosurgical Excision Procedure | Active comparator | Procedure: Loop Electrosurgical Excision Procedure30 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. |
| healthy population | No intervention | –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. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImiquimodAlso: IXIUMExperimental group will be treated with 16 applications of imiquimod and subsequently LEEP. | Drug | Imiquimod treatment plus Loop Electrosurgical Excision Procedure |
| Loop Electrosurgical Excision ProcedureAlso: LEEPActive comparator group will be treated with LEEP. | Procedure or surgery | Imiquimod treatment plus Loop Electrosurgical Excision Procedure, Loop Electrosurgical Excision Procedure |
Primary outcome
Number of participants with histological regression of High-grade squamous intraepithelial lesion (HSIL)
Time frame: 3 years
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
1 secondary outcome
Correlation between vaginal microbiome and immunological response
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Imiquimod and Loop Electrosurgical Excision Procedure in people with HSIL, High-Grade Squamous Intraepithelial Lesions and Vaginal Microbiome, run by Barretos Cancer Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with histological regression of High-grade squamous intraepithelial lesion (HSIL) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2025.