This phase I trial tests the safety, side effects and effectiveness of self-administered artesunate vaginal inserts (pessaries) in treating high grade cervical intraepithelial neoplasia (CIN). Cervical abnormalities are usually caused by human papillomavirus (HPV) and may progress to cancer. Treatment usually includes surgical removal using loop electrosurgical excision procedure (LEEP), however, access may be limited in rural areas and can be associated with side effects that can be long term and lead to premature births in future pregnancies. Artesunate is an anti-malarial drug that may kill cells infected with HPV while not affecting healthy cells. Self-administered artesunate pessaries may be safe, tolerable and effective in treating women with high grade CIN.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06165614.
PRIMARY OBJECTIVE:
I. To investigate the safety of self-administered artesunate pessaries (vaginal inserts) among HIV-positive and HIV-negative women with cervical precancerous lesions referred for excision in Kenya.
SECONDARY OBJECTIVES:
I. To investigate adherence to self-administered artesunate pessaries (vaginal inserts) for cervical precancer treatment among HIV-positive and HIV-negative women.
II. To evaluate change in lesion size following self-administered artesunate pessaries (vaginal inserts) for cervical precancer treatment among HIV-positive and HIV-negative women.
III. To investigate the rate of histologic regression to CIN1 or less following self-administered artesunate pessaries among participants with CIN2 or worse on biopsy, among HIV-positive and HIV-negative women.
IV. To investigate acceptability of self-administered artesunate pessaries for cervical precancer treatment among HIV-positive and HIV-negative women in Kenya.
EXPLORATORY OBJECTIVES:
I. To investigate longitudinal changes in HPV infection following intravaginal artesunate pessary use among HIV-positive and HIV-negative women.
II. To investigate longitudinal changes in cervical microbiome following intravaginal artesunate pessary use among HIV-positive and HIV-negative women.
III. To investigate longitudinal changes in the expression of biomarkers of local immune activation following intravaginal artesunate pessary use among HIV-positive and HIV-negative women.
IV. To investigate changes in artemisinin drug resistance patterns for treatment of malaria, if any, among study participants among HIV-positive and HIV-negative women.
OUTLINE:
Patients receive artesunate pessaries self-administered vaginally once daily (QD) for 5 days on weeks 1, 3, 5 and 7. Patients undergo colposcopy with biopsy at screening and at weeks 8, 14, 24, 36 and/or 48. Patients without disease response at week 14 and patients with persistent disease at weeks 24, 36, or 48 undergo LEEP. Additionally, patients undergo blood sample collection, self-collected vaginal swabs, and pelvic examination throughout the study.
After completion of study treatment, patients are followed up for up to 48 weeks.
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
Principal InvestigatorChemtai Mungo
