Predicting Response In Cervical Intraepithelial Neoplasia to Topical Imiquimod Treatment

Condition(s) studied

Investigational drug(s) / intervention(s)

Imiquimod: Imiquimod 5% will be administered in the evening by either a vaginal applicator or administered on a vaginal tampon for three times a week during 16 weeks. Treatment efficacy will be evaluated after 20 weeks, by colposcopy with diagnostic biopsies, and at 6 months after completion of imiquimod therapy with cytology and if indicated histology.

3x vaginal swab for microbiome analysis: A vaginal swab will be taken from all patients at inclusion (before start of imiquimod), at colposcopy 20 weeks after start of imiquimod and at 6 months after completion of imiquimod treatment during follow-up appointment.

Expectative management: Expectative management of CIN 2 when preferred by the patient. Follow-up 6 months after baseline colposcopy with cytology and if indicated histology.

2x vaginal swab for microbiome analysis: A vaginal swab will be taken from all patients at inclusion and at 6 months after inclusion during follow-up appointment.

Study summary

Imiquimod is a good non-invasive treatment option for women with cervical high-grade squamous intraepithelial neoplasia (cHSIL), especially those with a possible (future) pregnancy wish. Complete response to imiquimod occurs in 55-73% of patients, however side-effects of imiquimod are common and can be extensive. Therefore, biomarkers which can predict response to imiquimod therapy are warranted, to increase therapy efficacy and to avoid side effects in patients who will not respond.

This prospective, multi-center cohort study aims to validate the potential of immune related biomarkers to predict the clinical response of patients with primary cHSIL to imiquimod, aims to explore the value of these immune biomarkers in recurrent/residual cHSIL to predict treatment responses for imiquimod and aims to explore their potential in spontaneous regression of cHSIL (CIN2).

Eligibility

Primary outcome measure(s)

• Confirm association of 'hot signature' immune infiltrates in cHSIL with complete clinical responses to imiquimod — Up to 3 years
  Confirm the relationship between a complete clinical response to imiquimod and the increased epithelial and stromal infiltration of CD4+ T cells, CD11c+ cells and/or M1-like macrophages as well as the decreased infiltration with FoxP3+ Tregs in primary cHSIL.
• Validate immune biomarker CIBI for imiquimod for predicting complete response in cHSIL — Up to 3 years
  Defined as the sum of the numbers of either epithelial or stromal CD4+/CD11c+/M1+ cells per square millimeter minus the number of FoxP3+ cells per square millimeter, with a complete response to imiquimod treatment in primary cHSIL.
• Determine the sensitivity and specificity of the CIBI in cHSIL — Up to 3 years
  Determine the sensitivity and specificity of the CIBI in patients with primary cHSIL lesions to estimate the predictive value for therapy efficacy upon imiquimod treatment.

Trial sites (15)

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