Clinical Trials Program

临床试验计划

• 批准号: 10224783
• 负责人: MARGARET M MADELEINE
• 金额: $ 19.96万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224783
• 关键词: Acetic Acids; Address; Adjuvant; Affect; Age; Algorithms; Area; Biological Assay; Caribbean region; Cervical; Cervical Cancer Screening; Cervical Intraepithelial Neoplasia; Cessation of life; Child; Clinical; Clinical Trials; Colposcopy; Communities; Correlative Study; Country; Cytology; Detection; Diagnosis; Disease; Dominican Republic; Dose; Enrollment; Goals; HIV; HIV Infections; Health; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Imaging technology; Immune; Immunoprevention; Improve Access; Incidence; Infrastructure; International; Latin America; Lead; Lesion; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Memory B-Lymphocyte; Methods; Monoclonal Antibodies; Operative Surgical Procedures; Outcome; Pap smear; Papillomavirus Transforming Protein E6; Participant; Patients; Persons; Peru; Population; Prevention; Provider; Quality of life; Randomized Controlled Trials; Recurrence; Regimen; Research; Resources; Risk; Schedule; Sirolimus; Site; Testing; Time; Triage; Vaccination; Vaccines; Visual; Woman; Youth; automated visual evaluation; base; cancer prevention; cervical cancer prevention; design; experience; girls; high risk; implementation facilitation; improved; improved outcome; low and middle-income countries; new technology; novel; overtreatment; point of care; premalignant; prevent; prevention service; programs; response; screening; standard of care; treatment strategy; tumor microenvironment

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.

项目总结-临床试验 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。 宫颈癌在拉丁美洲和加勒比地区（LAC）。每年有超过27万妇女死于宫颈癌 癌症，它不成比例地影响低收入和中等收入国家（LMIC）的妇女， 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 宫颈癌的发病率高于美国，艾滋病毒感染率也很高，特别是在弱势群体中， 关键人群。感染艾滋病毒的妇女和儿童（WLWH和CLWH）更有可能持续感染艾滋病毒。 HPV和高级别病变，并且他们比未感染HIV的妇女进展为癌症的风险更高。 满足低收入国家中有可能患上与人类乳头瘤病毒有关的癌症的艾滋病毒感染者的需要， 获得HPV疫苗以及更有效地筛查和治疗宫颈高度病变。相反 为了复制在高资源环境中使用的筛查所需的基础设施，临床试验提出， 在此寻求使用一种新预防和治疗方法的组合， 基础设施支持。我们将利用和加强西雅图和拉丁美洲和加勒比地区的现有研究能力 探索当地医疗服务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阳性儿童的最佳HPV疫苗接种时间表，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诊，并测试非手术方法，以改善 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：通过接种未暴露儿童的HPV免疫预防对于患有HPV感染的儿童并不是最佳的 艾滋病毒（CLWH）。我们将比较HIV感染青年（年龄）中的长期免疫（回忆）反应， 9-13入组时）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 癌前病变，减少过度治疗，便于实施。我们将开发一个更有效的 通过评估护理标准（巴氏试验和目视检查）检测高级别病变（CIN 2/3）的算法 HPV检测和更新的技术，包括HPV E6/E7表达和增强视觉 检查（伊娃）与自动视觉评价（AVE），相当于阴道镜。 试验3：评价非手术策略治疗诊断为高级别病变（CIN 2/3）， 来自试验2的WLWH，在手术前开始的9价HPV疫苗和西罗莫司的2x2析因试验中。 这些试验将由宫颈癌预防合作伙伴关系（C2 P2）中心进行，该中心将 与秘鲁、多米尼加共和国、西雅图的合作者一起，与国际外部科学和 社区顾问。这些团队在开展高质量临床试验和工作方面拥有丰富的经验 在中低收入国家预防HPV相关癌症，并改善艾滋病毒感染者的健康和生活质量。