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）

• 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
• 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

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.

项目摘要/摘要 随着宫颈癌死亡人数的持续上升，特别是在资源匮乏的情况下，我们 正在寻找更有效的预防宫颈癌的方法。在没有的情况下 细胞学和人乳头状瘤病毒为基础的宫颈癌筛查，专家支持筛查 应用醋酸(VIA)后对宫颈进行肉眼检查以突出癌前病变或 癌变异常。如果识别的乙酰白图案被感知为异常，则 宫颈上皮可以通过冷冻(冷冻)或加热(热消融)来消融。 “见即治”入路或大环切除变形区(LLETZ)。 这种宫颈癌筛查和治疗的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)，那里有一些 世界上宫颈癌发病率最高的国家。我们的团队进行了一项最大规模的随机 在SSA进行的对照试验对这些治疗方法进行了比较。我们的预赛 结果表明，这些治疗方法对感染艾滋病毒的妇女的疗效几乎降低了50%。 (WLWH)。正如这些发现所证明的那样，消除宫颈癌作为一个重要的公众 健康疾病要求采取和实施易于获得的战略， 负担得起，可接受，在WLWH同样有效。一种潜在的治疗剂 需要进一步调查的是一种含有蛋白酶抑制剂(PI)的阴道胶囊。 Lopinavir和Ritonavir(LPV/r)，这两种药物具有已知的抗癌和HPV活性。总目标 这项试验的重点是找到新的、非侵入性的、易于扩展的解决方案，以解决 宫颈癌的二级预防，特别是在世界卫生组织中。这项研究的中心目标是 评价LPV/r阴道胶囊单独或联合应用的安全性和可接受性 通过有资格接受消融治疗的阳性妇女进行热消融治疗。我们会 在宫颈癌预防中招募180名参加宫颈癌筛查的妇女 赞比亚的项目诊所。参与者(n=180)将根据艾滋病毒状况和 随机接受1)LPV/R或安慰剂治疗3周，然后在4周进行热消融 或2)LPV/r或安慰剂单独治疗3周，6个月重复VIA，热消融治疗 宫颈病变持续VIA阳性者。在180名女性中，有20名将是 随机进入正常护理的对照队列，如果符合条件，立即给予助教。预期中的 这项工作的结果是产生了这种新的LPV/r治疗是安全的和 可用于筛查阳性的妇女的治疗或辅助治疗。由此产生的结果 这项研究将为在SSA队列中大规模研究LPV/r奠定基础。