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-临床试验方案