Clinical Trials Program

临床试验计划

• 批准号: 10601389
• 负责人: MARGARET M MADELEINE
• 金额: $ 25.72万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10601389
• 关键词: Clinical; Trials; Program

PROJECT SUMMARY – CLINICAL TRIALS PROGRAM The goal of the Clinical Trials Program is to address the dual burden of HIV infection and HPV-associated cervical cancer in Latin America and the Caribbean (LAC). Over 270,000 women die every year of cervical cancer, and it disproportionately affects women in low- and middle-income countries (LMICs) where approximately 90% of cervical cancer deaths occur. Peru and the Dominican Republic experience a 3-fold higher incidence of cervical cancer than the US, as well as high rates of HIV infection, especially in vulnerable key populations. Women and children living with HIV (WLWH and CLWH) are more likely to have persistent HPV and high-grade lesions, and they are at higher risk of progression to cancer than HIV-uninfected women. Addressing the needs of HIV-infected persons at risk for HPV-associated cancers in LMICs involves improving access to HPV vaccines and more effective screening for and treatment of cervical high-grade lesions. Instead of replicating the infrastructure needed for screening used in high-resource settings, the clinical trials proposed here seek to use a new combination of prevention and treatment methods aimed at point-of-care with low- infrastructure support. We will leverage and strengthen existing research capacity in Seattle and the LAC sites to explore sustainable solutions that are acceptable to local providers and patients. This includes investigating optimal HPV vaccine schedules for HIV+ children, assessing new HPV tests and visual imaging technologies to help clinicians to perform high-quality screening and triage, and testing non-surgical approaches to improve outcomes of cervical cancer precursors among WLWH. Toward this goal we will conduct three clinical trials: Trial 1: HPV immunoprevention by vaccination of unexposed children is not optimized for children living with HIV (CLWH). We will compare longer-term immune (anamnestic) responses among HIV-infected youth (ages 9-13 at the time of enrollment) after 1, 2, or 3 doses of 9-valent HPV vaccine. Trial 2: Cervical cancer screening and triage among WLWH needs to be optimized to improve detection of precancerous lesions, reduce overtreatment and facilitate implementation. We will develop a more efficient algorithm to detect high-grade lesions (CIN2/3) by assessing standard of care (Pap test and visual inspection with acetic acid), HPV testing, and newer technologies including HPV E6/E7 expression and enhanced visual inspection (EVA) with automated visual evaluation (AVE), comparable to colposcopy. Trial 3: Evaluating non-surgical strategies for treatment of high-grade lesions (CIN2/3) diagnosed in WLWH from Trial 2 in a 2x2 factorial trial of 9-valent HPV vaccine and sirolimus initiated before surgery. These trials will be framed by the Cervical Cancer Prevention Partnership (C2P2) Center, that brings together collaborators in Peru, the Dominican Republic, Seattle, with international external scientific and community advisors. The teams have extensive experience conducting high-quality clinical trials and working to prevent HPV-related cancers in LMICs and improve health and quality of life for persons living with HIV.

项目摘要-临床试验计划 临床试验计划的目标是解决艾滋病毒感染和HPV相关的双重负担 拉丁美洲和加勒比(LAC)的宫颈癌。每年有超过27万名妇女死于宫颈疾病 癌症，而且它对低收入和中等收入国家(LMIC)的妇女影响不成比例 大约90%的宫颈癌死亡发生在癌症中。秘鲁和多米尼加共和国经历了3倍的 宫颈癌发病率高于美国，艾滋病毒感染率也较高，特别是在脆弱人群中 关键人群。感染艾滋病毒的妇女和儿童(WLWH和CLWH)更有可能患有持续性 HPV和高级别病变，她们比未感染艾滋病毒的妇女患癌症的风险更高。 解决LMIC中HPV相关癌症风险的艾滋病毒感染者的需求需要改进 获得HPV疫苗，更有效地筛查和治疗宫颈高级别病变。取而代之的是 在复制在高资源环境下使用的筛查所需的基础设施方面，临床试验建议 在这里，寻求使用一种新的预防和治疗方法相结合的目的，旨在护理点与低- 基础设施支撑。我们将利用和加强西雅图和LAC站点的现有研究能力 探索当地提供者和患者都能接受的可持续解决方案。这包括调查 针对HIV+儿童的最佳HPV疫苗计划，评估新的HPV检测和视觉成像技术 帮助临床医生进行高质量的筛查和分类，并测试非手术方法以改进 WLWH人群中宫颈癌先兆的结局。为了实现这一目标，我们将进行三项临床试验： 试验1：未接触HPV的儿童接种疫苗进行的HPV免疫预防对患有HPV的儿童并不优化 艾滋病毒(CLWH)。我们将比较感染艾滋病毒的青年(AGE)的长期免疫(记忆)反应 在接种1、2或3剂9价HPV疫苗后)。 试验2：WLWH中的宫颈癌筛查和分诊需要优化，以提高对 减少癌前病变，减少过度治疗，便于实施。我们将开发一种更高效的 通过评估护理标准(巴氏试验和目视检查)检测高级别病变的算法(CIN2/3 HPV检测，以及更新的技术，包括HPV E6/E7表达和增强的视力 自动视觉评估(AVE)检查(EVA)，可与阴道镜检查相媲美。 试验3：评估高级别病变的非手术治疗策略(CIN2/3) WLWH来自手术前开始的9价HPV疫苗和西罗莫司2x2因子试验中的试验2。 这些试验将由宫颈癌预防伙伴关系(C2P2)中心制定，这将带来 秘鲁、多米尼加共和国、西雅图的合作者与国际外部科学和 社区顾问。这些团队拥有进行高质量临床试验和工作的丰富经验 预防LMICs中HPV相关癌症，改善艾滋病毒携带者的健康和生活质量。