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 临床试验计划的目的是解决HIV感染的双重伯恩和HPV相关的 拉丁美洲和加勒比海（LAC）的宫颈癌。每年超过270,000名宫颈死亡 癌症，这对低收入和中等收入国家（LMIC）的妇女不成比例地影响 大约90％的宫颈癌死亡发生。秘鲁和多米尼加共和国经历了3倍 宫颈癌事件高于美国，以及艾滋病毒感染率高，尤其是在脆弱的情况下 关键人群。患有艾滋病毒（WLWH和CLWH）的妇女和儿童更有可能持久 HPV和高级病变，与艾滋病毒未感染的妇女相比，它们的癌症进展风险更高。 满足有HPV相关癌症风险的HIV感染者的需求，包括改善 获取HPV疫苗和更有效的筛查和治疗宫颈高级病变。反而 为了复制用于高资源设置所需的筛选所需的基础设施，提出了临床试验 在这里寻求使用旨在以低位的护理的预防和治疗方法的新组合 基础架构支持。我们将利用和增强西雅图和LAC网站的现有研究能力 探索当地提供者和患者可以接受的可持续解决方案。这包括调查 HIV+儿童的最佳HPV疫苗时间表，评估新的HPV测试和视觉成像技术 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中宫颈癌前体的结果。为了实现这一目标，我们将进行三项临床试验： 试验1：未针对未暴露儿童进行疫苗接种HPV免疫预防 艾滋病毒（CLWH）。我们将比较感染HIV的青年（年龄 1、2或3剂9值HPV疫苗后，在入学时为9-13。 试验2：需要优化WLWH中的宫颈癌筛查和分类，以改善对检测的检测 癌前病变，减少过度治疗并促进实施。我们将发展一个更有效的 通过评估护理标准（PAP测试和视觉检查）来检测高级病变（CIN2/3）算法 乙酸），HPV测试和包括HPV E6/E7表达和增强视觉的新技术 具有自动视觉评估（AVE）的检查（EVA），与阴道镜相当。 试验3：评估在诊断为高级病变（CIN2/3）的非手术策略 在手术前启动的9值HPV疫苗和Sirolimus的2x2阶乘试验中，试验2的WLWH。 这些试验将由宫颈癌预防伙伴关系（C2P2）中心构建，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 为了防止LMIC中与HPV相关的癌症，并改善艾滋病毒患者的健康和生活质量。