RepurPosed AntiretrOviraL ThErapieS to EliminAte Cervical Cancer (POLESA Trial)

重新利用抗逆转录病毒疗法来消除宫颈癌（POLESA 试验）

基本信息

批准号：
10738121
负责人：
Leeya F Pinder
金额：
$ 51.13万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10738121
关键词：
Ablation Acetic Acids Address Adopted Adoption Adverse event Africa South of the Sahara Atopobium vaginae Biological Assay Cancer Etiology Cancerous Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cervix Uteri Cessation of life Clinic Clinical Trials Cold Therapy Conventional Surgery Cytology Data Disease Electrosurgery Eligibility Determination Enrollment Epithelium Excision Exudate Formulation Freezing Gel Generations Goals HIV HPV-High Risk Heating Human Papillomavirus Human papilloma virus infection In Vitro Interferon Type II Interleukin-10 Interleukin-2 Interleukin-4 Interleukin-6 Intravaginal Administration Investigation Kenya Lesion Lopinavir/Ritonavir Malignant neoplasm of cervix uteri Methods Outcome Participant Pattern Persons Placebos Prevention program Protease Inhibitor Public Health Questionnaires Randomized Randomized, Controlled Trials Research Resource-limited setting Secondary to Self Administration Signal Transduction Structure TNF gene Techniques Telephone Testing Therapeutic Therapeutic Agents Thermal Ablation Therapy Time Transforming Growth Factor beta Vagina Visit Visual Woman Work Zambia anti-cancer antiretroviral therapy arm capsule cervical cancer prevention cervicovaginal chronic infection cohort cytokine innovation low and middle-income countries multiplex assay novel premalignant response safety assessment safety study scale up screening standard of care treatment as usual treatment comparison treatment strategy trend tumor-immune system interactions

项目摘要

Project Summary/Abstract As the death toll from cervical cancer continues to rise, particularly in low-resource settings, we are in search of more effective approaches to cervical cancer prevention. In the absence of cytology- and HPV-based cervical cancer screening, experts have endorsed screening of the cervix by visual inspection after application of acetic acid (VIA) to highlight precancerous or cancerous abnormalities. If the recognized acetowhite pattern is perceived to be abnormal, the cervical epithelium is either ablated by freezing (cryotherapy) or heating (thermal ablation) in a “see and treat” approach or excised with a large loop excision of the transformation zone (LLETZ). This approach to cervical cancer screening and treatment has been widely adopted in low- and middle-income countries (LMICs), notably in sub-Saharan Africa (SSA), which has some of the world’s highest rates of cervical cancer. Our team conducted one of the largest randomized controlled trials ever conducted in SSA comparing these treatment approaches. Our preliminary results suggest that these treatments are almost 50% less effective for women living with HIV (WLWH). As evidenced by these findings, the elimination of cervical cancer as a significant public health disease requires the adoption and implementation of strategies that are easily accessible, affordable, acceptable and are equally efficacious in WLWH. One potential therapeutic agent that warrants further investigation is a vaginal capsule containing the protease inhibitors (PIs) Lopinavir and Ritonavir (LPV/r), which have known anti-cancer and HPV activity. The overall goal of this trial is to find new, non-invasive, easily scalable solutions that address the profound gap in secondary cervical cancer prevention, particularly among WLWH. The central aim of this study is to assess the safety and acceptability of the LPV/r vaginal capsule given alone or in combination with thermal ablation to treat VIA positive women who are eligible for ablative therapy. We will enroll 180 women who present for cervical cancer screening in a Cervical Cancer Prevention Program clinic in Zambia. Participants (n=180) will be stratified based on HIV status and randomized to receive 1) LPV/r or placebo for 3 weeks followed by thermal ablation at 4 weeks or 2) LPV/r or placebo alone for 3 weeks with repeat VIA at 6 months and thermal ablation for those with persistent VIA positive cervical lesions. Twenty of the 180 VIA positive women will be randomized to a comparator cohort of usual care with immediate TA if eligible. The expected outcome of this work is the generation of evidence that this novel LPV/r treatment is safe and acceptable for use as treatment or adjunct in women who screen VIA positive. Results from this study will lay the groundwork for a large-scale study of LPV/r in a SSA cohort.

项目概要/摘要随着宫颈癌死亡人数持续上升，特别是在资源匮乏的地区，我们在缺乏宫颈癌预防措施的情况下，正在寻找更有效的方法。基于细胞学和 HPV 的宫颈癌筛查，专家们赞同对宫颈癌进行筛查应用醋酸（VIA）后通过目视检查子宫颈以突出癌前或癌前病变如果识别出的醋酸白图案被认为是异常的，则宫颈上皮可以通过冷冻（冷冻疗法）或加热（热消融）的方式消融。 “观察并治疗”方法或通过大环切除转化区 (LLETZ) 进行切除。这种宫颈癌筛查和治疗方法已在低收入和低收入人群中广泛采用。中等收入国家 (LMIC)，特别是撒哈拉以南非洲 (SSA)，该地区拥有一些我们的团队进行了世界上最高的宫颈癌发病率之一。我们在 SSA 进行的初步对照试验比较了这些治疗方法。结果表明，这些治疗方法对感染艾滋病毒的女性的效果几乎降低了 50% (WLWH) 这些发现证明，消除宫颈癌是一个重要的公众问题。健康疾病需要采取和实施容易获得的策略，一种经济实惠、可接受且对 WLWH 同样有效的治疗剂。值得进一步研究的是含有蛋白酶抑制剂（PI）的阴道胶囊洛匹那韦和利托那韦 (LPV/r) 具有已知的抗癌和 HPV 活性。这项试验的目的是寻找新的、非侵入性的、易于扩展的解决方案，以解决在二级宫颈癌预防，特别是 WLWH 的这项研究的中心目标是。评估单独或联合使用 LPV/r 阴道胶囊的安全性和可接受性我们将采用热消融治疗符合消融治疗资格的 VIA 阳性女性。在宫颈癌预防项目中招募 180 名接受宫颈癌筛查的女性赞比亚的项目诊所将根据艾滋病毒状况和情况对参与者（n=180）进行分层。随机接受 1) LPV/r 或安慰剂 3 周，然后在 4 周时进行热消融或 2) 单独使用 LPV/r 或安慰剂 3 周，并在 6 个月时重复 VIA 和热消融 180 名 VIA 阳性女性中，有 20 名患有持续性 VIA 阳性宫颈病变。如果符合条件，则随机分配到接受常规护理的对照组并立即进行 TA。这项工作的成果是产生了证据，证明这种新型 LPV/r 治疗方法是安全且有效的。可以用作筛查 VIA 结果呈阳性的女性的治疗或辅助疗法。研究将为 SSA 队列中 LPV/r 的大规模研究奠定基础。