CANCER GENETICS NETWORK (CGN) OVARIAN SCREENING PILOT TRIAL IN HIGH RIS WOMEN

癌症遗传学网络 (CGN) 在高危女性中进行卵巢筛查试点试验

• 批准号: 7719027
• 负责人: Claudine Isaacs
• 金额: $ 2.14万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719027
• 关键词: Age; Algorithms; BRCA1 gene; BRCA2 Mutation; BRCA2 gene; Bilateral oophorectomy; Biological Markers; Blood; Breast; CA-125 Antigen; Cancer Genetics Network; Carcinomatosis; Categories; Classification; Clinical; Computer Retrieval of Information on Scientific Projects Database; Databases; Decision Making; Disease; Early Diagnosis; Effectiveness; Eligibility Determination; Environmental Exposure; Evaluation; Family; Family history of; Funding; Genes; Goals; Grant; Health; High Risk Woman; Histologic; Hour; Incidence; Inherited; Institution; Laboratories; Malignant neoplasm of ovary; Measurement; Measures; Menopausal Status; Moths; Mutation; National Cancer Institute; Normal Range; Operative Surgical Procedures; Ovarian; Ovariectomy; Participant; Patients; Peritoneal; Physicians; Plasma; Postmenopause; Predictive Value; Quality of life; Questionnaires; Recording of previous events; Recruitment Activity; Recurrence; Research; Research Personnel; Resources; Risk; Sampling; Screening for Ovarian Cancer; Screening procedure; Shipping; Ships; Site; Solutions; Source; Specificity; Staging; Survival Rate; Test Result; Testing; Time; Triage; Tumor Markers; Ultrasonography; United States Food and Drug Administration; United States National Institutes of Health; Upper arm; Week; Woman; abstracting; base; cancer diagnosis; cancer risk; clinical Diagnosis; design; lifetime risk; malignant breast neoplasm; pilot trial; programs; prophylactic; prospective; repository; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As of 2/07/06: Despite new therapies, the five-year survival rate for patients with ovarian cancer has not changed significantly over the past thirty years. When detected in early stages, however, survival from ovarian cancer is usually better than when it is detected at later stages. This study is an ovarian cancer screening protocol, using a test called CA125. CA125 is an FDA approved marker for detecting recurrence of disease in women who have already had ovarian cancer. This research study aims to determine if CA125 is helpful in the early detection of ovarian cancer among women at high-risk for ovarian cancer due to a family history of breast or ovarian cancer, or an inherited alteration in genes called BRCA1 and BRCA2. A secondary goal of this study is to assess the impact of ovarian cancer screening on women's quality of life. This study is part of the Cancer Genetics Network (CGN) sponsored by the National Cancer Institute (NCI) and will evaluate study participants over a two to three-year period testing the effectiveness of CA125. Participation in this project will also help identify women in a high-risk category with the hope of detecting ovarian cancer early. Patients in this risk group will be referred by their physicians for ultrasound, laparascopy and/or surgery if it is indicated by the results of these tests. Initial Abstract: Women with a BRCA1 and BRCA2 mutation have an increased lifetime risk for ovarian cancer of 10-20 fold higher than women without such mutations. Even after prophylactic surgery women may develop peritoneal carcinomatosis, a disease clinically and histologically identical to late stage ovarian cancer. We hypothesize that for women with a high risk of developing ovarian cancer, screening for ovarian cancer or peritoneal carcinomatosis with longitudinal CA125 measurements and ultrasound may permit earlier detection than current practice. Such a screening trial would also permit initial estimation of the incidence of ovarian cancer by age and menopausal status. There are four specific aims of this trial: 1) determine the feasibility of prospective programs, and identify the logistical issues of screening and their solutions within this framework; 2) establish normal ranges and distribution within and between high risk women for CA125 values over time, with sub-classification by pre/post-menopausal status, ERT usage (yes/no), and prophylactic oophorectomy (yes/no); 3) obtain estimates of the specificity and positive predictive value of ROCA (risk of ovarian cancer algorithm)suitable for desgning a definitve trial of screening for ovarian cancer in high risk women; 4) establish a longitudinal serum and plasma bio-repository for retrospective evaluation of other promising biomarkers with special relevance to inherited ovarian and breast cancer risk. The CGN ovarian screening trial is a mulit-center trial, recruiting women from families with high risk for ovarian cancer. The design is a prospective one=armed study with decision making based on the tumor marker CA125 levels measured in blood at baseline and every three-moth interval. Subjects will be recruited over a period of twelve moths, screened for at lease one year and for up to two years if recruited at the beginning of the recruitment period, and followed for clinical diagnosis of cancer for an additional year. For each new CA125 measurement, the ROCA will be calculated and stored in the CGN clinical database. ROCA calculates the risk of having ovarian cancer based on age, family history, and longitudinal CA125 values and then triages the subject according to the level of risk. The CA125 value and the action to be taken will be emailed to the site project manager immediately upon availability of the risk of having ovarian cancer. The choice of action will depend on the level of risk, and the site will be responsible for contacting the patient. Subjects will also be asked to complete a baseline questionnaire asking about health history, environmental exposures, and family history, as well as brief questionnaires at each blood draw regarding any changes in the subject's health since the last CA125 test. The GCRC will perform blood draws on study participants, and will spin samples within 24 hours of each draw. The GCRC will also store samples at -70o C until shipping to the central laboratory every week.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 截至 2006 年 2 月 7 日： 尽管出现了新的疗法，但卵巢癌患者的五年生存率在过去三十年中没有显着变化。 然而，在早期发现时，卵巢癌的生存率通常比在晚期发现时要好。 这项研究是一项卵巢癌筛查方案，使用名为 CA125 的测试。 CA125 是 FDA 批准的标记物，用于检测已患有卵巢癌的女性的疾病复发。 本研究旨在确定 CA125 是否有助于因乳腺癌或卵巢癌家族史或 BRCA1 和 BRCA2 基因遗传性改变而导致卵巢癌高危女性的卵巢癌早期检测。 这项研究的第二个目标是评估卵巢癌筛查对女性生活质量的影响。 这项研究是美国国家癌症研究所 (NCI) 赞助的癌症遗传学网络 (CGN) 的一部分，将在两到三年的时间内评估研究参与者，测试 CA125 的有效性。 参与该项目还将有助于识别属于高危类别的女性，以期及早发现卵巢癌。 如果这些测试结果表明，该风险组的患者将被医生转诊进行超声检查、腹腔镜检查和/或手术。 初始摘要： 具有 BRCA1 和 BRCA2 突变的女性终生患卵巢癌的风险比没有此类突变的女性高 10-20 倍。即使在预防性手术后，女性也可能出现腹膜癌病，这种疾病在临床和组织学上与晚期卵巢癌相同。我们假设，对于罹患卵巢癌的高风险女性，通过纵向 CA125 测量和超声筛查卵巢癌或腹膜癌病可能比目前的做法更早发现。这样的筛查试验还可以根据年龄和绝经状态初步估计卵巢癌的发病率。该试验有四个具体目标：1）确定前瞻性项目的可行性，并在此框架内确定筛选的后勤问题及其解决方案； 2) 随着时间的推移，建立高危女性内部和之间 CA125 值的正常范围和分布，并按绝经前/绝经后状态、ERT 使用（是/否）和预防性卵巢切除术（是/否）进行细分； 3）获得ROCA（卵巢癌风险算法）的特异性和阳性预测值的估计，适合设计高风险女性卵巢癌筛查的确定性试验； 4）建立纵向血清和血浆生物样本库，用于回顾性评估与遗传性卵巢癌和乳腺癌风险特别相关的其他有前景的生物标志物。 CGN 卵巢筛查试验是一项多中心试验，招募来自卵巢癌高风险家庭的女性。该设计是一项前瞻性单臂研究，根据基线和每三个月间隔测量的血液中肿瘤标志物 CA125 水平做出决策。受试者将在十二个月内招募，筛选至少一年，如果在招募期开始时招募，则筛选最多两年，并再跟踪一年进行癌症临床诊断。对于每个新的 CA125 测量，将计算 ROCA 并将其存储在 CGN 临床数据库中。 ROCA根据年龄、家族史和纵向CA125值计算患卵巢癌的风险，然后根据风险水平对受试者进行分类。一旦获得卵巢癌风险，CA125 值和要采取的行动将立即通过电子邮件发送给现场项目经理。行动的选择将取决于风险级别，并且该站点将负责联系患者。受试者还将被要求完成一份基线调查问卷，询问健康史、环境暴露和家族史，以及在每次抽血时填写关于自上次 CA125 测试以来受试者健康状况任何变化的简短调查问卷。 GCRC 将对研究参与者进行抽血，并在每次抽血后 24 小时内旋转样本。 GCRC 还将样品储存在 -70o C 下，直到每周运送到中心实验室。