Cancer of the cervix – which is the opening of the womb, is a leading cause of cancer death in Kenya and other low-income countries. Cervical cancer can be prevented if early changes in the cervix, called cervical precancer, are detected through screening and treated. Treatment for certain women with cervical precancer includes a procedure called Loop Electrosurgical Excision Procedure (LEEP), - during which the area of the cervix with precancer is removed. In countries like Kenya, this LEEP procedure is only available in referral hospitals which have trained consultants, and as a result it is difficult for women who need this treatment to it if they live far from a referral hospital. This LEEP procedure also increases the chance of a woman having not being able to carry a pregnancy to full term, because the cervix is shorter after the procedure. For these reasons, scientists are looking for alternative treatments for cervical precancer that can be used instead of LEEP. One such treatment that is being studied a medication called Artesunate that can be applied as a vaginal pessary directly by a woman for treatment of cervical precancer. Early studies in the United States have shown that Artesunate may be able to treat cervical precancer and women who use it may not need to get a LEEP procedure. This study is being done in order to understand whether women with cervical precancer in Kenya who need a LEEP procedure can instead be treated with Artesunate pessaries. The goals of the study are to understand whether it is safe for women to use artesunate pessaries in Kenya, whether women will use them as instructed (what doctors call adherence), whether women who use this pessary can have improvement or cure of their cervical precancer, (clinical response), and whether women using artesunate pessaries will find it an acceptable treatment.

Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs) which bear 90% of deaths. Access to cervical precancer treatment is key to prevention cervical cancer in LMICs. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer.

Objectives: This is a Phase I trial  among 18 HIV-positive and HIV-negative women in Kenya investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be safety of self-administered artesunate pessaries. Secondary objectives will evaluate adherence, change in lesion size, histologic regression to CIN1 or less, and acceptability of artesunate pessaries. The central hypothesis of this study is that self-administered intravaginal Artesunate will be safe, and result in a clinical response among both HIV-positive and HIV-negative women with cervical precancer in LMICs.

Methods: The study duration is 48 weeks. Participants will self-administer 200 mg of Artesunate pessary (vaginal insert) daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (Artesunate self-administration on Weeks 1, 3, 5, 7). Safety and adherence will be assessed through review of symptoms diary and biweekly follow-up during the treatment phase. Clinical response, defined as a reduction in lesion size by 1 or more quadrants or regression to CIN1 or less will be assessed at week14. Participants with no improvement in lesion grade or size at week 14 will have excision. Participants with improvement in lesion grade or size at week 14 will be observed until Week 24, at which time they will have excision if a visible lesion is present or CIN2 or worse is detected on biopsy. Participants without a lesion at Week 24 or have had regression to CIN1 or less will be followed at Weeks 36, and 48 for surveillance. Any CIN2 or worse at follow-up will be managed with excision. Acceptability will be evaluated at Week 8 using a questionnaire and in-depth interviews. Data collection will be via electronic database. Data analysis will include quantitative and qualitative analysis.