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.

项目摘要——临床试验计划 临床试验计划的目标是解决 HIV 感染和 HPV 相关的双重负担 拉丁美洲和加勒比地区 (LAC) 的宫颈癌。每年有超过 270,000 名女性死于宫颈癌 癌症，并且它对低收入和中等收入国家 (LMIC) 的妇女影响尤为严重，其中 大约 90% 的死亡发生在宫颈癌。秘鲁和多米尼加共和国经历了三倍 宫颈癌发病率高于美国，艾滋病毒感染率也很高，尤其是在弱势群体中 重点人群。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，与未感染 HIV 的女性相比，她们进展为癌症的风险更高。 满足中低收入国家中面临 HPV 相关癌症风险的 HIV 感染者的需求涉及改善 获得 HPV 疫苗以及更有效地筛查和治疗宫颈重度病变。反而 临床试验建议复制在资源丰富的环境中使用的筛查所需的基础设施 这里寻求使用一种新的预防和治疗方法相结合的方法，旨在以低水平进行护理 基础设施支持。我们将利用和加强西雅图和拉美地区现有的研究能力 探索当地医疗服务提供者和患者可接受的可持续解决方案。这包括调查 针对 HIV + 儿童的最佳 HPV 疫苗接种计划，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诊，并测试非手术方法以改善 WLWH 中宫颈癌前兆的结果。为了实现这一目标，我们将进行三项临床试验： 试验 1：通过给未接触过病毒的儿童接种疫苗来进行 HPV 免疫预防，对于患有 HPV 的儿童来说并不是最佳选择 艾滋病毒（CLWH）。我们将比较感染艾滋病毒的青少年（年龄 接种 1、2 或 3 剂 9 价 HPV 疫苗后（注册时的 9-13）。 试验 2：需要优化 WLWH 中的宫颈癌筛查和分诊，以提高宫颈癌的检出率 癌前病变，减少过度治疗，便于实施。我们将开发更高效的 通过评估护理标准（巴氏试验和目视检查）来检测高级病变（CIN2/3）的算法 醋酸）、HPV 检测以及更新的技术，包括 HPV E6/E7 表达和增强视觉 与阴道镜检查（EVA）相结合的自动视觉评估（AVE）。 试验 3：评估非手术策略治疗高级别病变 (CIN2/3) 来自手术前启动的 9 价 HPV 疫苗和西罗莫司的 2x2 析因试验中试验 2 的 WLWH。 这些试验将由宫颈癌预防合作伙伴 (C2P2) 中心组织，该中心将带来 秘鲁、多米尼加共和国、西雅图的合作者与国际外部科学界和 社区顾问。该团队在进行高质量临床试验和工作方面拥有丰富的经验 预防中低收入国家中与 HPV 相关的癌症，并改善艾滋病毒感染者的健康和生活质量。