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

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

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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.

项目摘要/摘要随着宫颈癌的死亡人数持续上升，尤其是在低资源环境中，我们正在寻找预防宫颈癌的更有效方法。在没有基于细胞学和HPV的宫颈癌筛查，专家已认可筛查在应用乙酸后通过视觉检查（VIA）通过视觉检查突出癌前或癌性异常。如果认为公认的乙硫酸盐模式是异常的宫颈上皮是通过冷冻（冷冻疗法）或加热（热消融）消融 “看到和治疗”方法或在转换区域（Lletz）的大循环切除术时出色。这种宫颈癌筛查和治疗的方法已在低 - 和中等收入国家（LMIC），特别是在撒哈拉以南非洲（SSA），其中一些世界上最高的宫颈癌。我们的团队进行了最大的随机性之一在SSA中进行的对照试验比较了这些治疗方法。我们的初步结果表明，这些治疗对艾滋病毒妇女的效果几乎降低了50％（wlwh）。这些发现证明了消除宫颈癌作为重要的公众健康疾病需要采用和实施容易访问的策略，负担得起，可接受，在WLWH中同样有效。一种潜在的治疗剂保证进一步研究是一个阴道胶囊，其中包含蛋白酶抑制剂（PIS） Lopinavir和Ritonavir（LPV/R），它们已知抗癌和HPV活性。总体目标这项试验是找到新的，无创的，易于扩展的解决方案，以解决深远的差距次要宫颈癌预防，特别是在WLWH中。这项研究的核心目的是评估单独或组合的LPV/R阴道胶囊的安全性和可接受性通过热消融，可以通过有资格进行消融治疗的正妇女治疗。我们将在预防宫颈癌预防宫颈癌筛查的180名妇女招生赞比亚的计划诊所。参与者（n = 180）将根据艾滋病毒状况进行分层随机接收1）LPV/R或安慰剂3周，然后在4周时进行热消融或2）LPV/R或单独安慰那些通过阳性宫颈病变持续存在的人。 180名通过正面女性中有二十个将是如果符合条件，则随机分配给常规护理的比较人群。预期这项工作的结果是有证据表明这种新颖的LPV/R治疗是安全的，并且可以用作治疗或辅助的妇女在筛查阳性的妇女中接受。结果研究将为SSA队列中的LPV/R进行大规模研究奠定基础。