Phase II Study of Sulindac in Oral Premalignant Lesions

舒林酸治疗口腔癌前病变的 II 期研究

• 批准号: 7114261
• 负责人: JAY O BOYLE
• 金额: $ 6.5万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114261
• 关键词: Asians; India; alcoholism /alcohol abuse; biomarker; cancer prevention; cancer risk; carbopolycyclic compound; chemoprevention; clinical research; clinical trial phase II; cyclooxygenase inhibitors; drug screening /evaluation; genetic polymorphism; geographic difference; histopathology; human subject; human therapy evaluation; mouth neoplasms; neoplasm /cancer epidemiology; nonsteroidal antiinflammatory agent; oral leukoplakia; p53 gene /protein; preneoplastic state; tobacco abuse

DESCRIPTION (provided by applicant): The proposed trial is a phase II randomized, double-blind, placebo-controlled chemoprevention pilot trial of 150 mg bid sulindac for 6 months for oral premalignant lesions (OPL). The objective is to determine the feasibility of conducting such studies through an international collaboration between Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and the Amrita Institute of Medical Sciences (AIMS) in Kerala, India. This State has one of the highest incidences of oral cancer and leukoplakia in the world due to habits of tobacco exposure. The study seeks also to determine the clinical efficacy and safety of sulindac against OPL and to determine the effect of sulindac on biomarkers in OPL tissue. The biomarkers are DNA ploidy, Ki67 IHC, p53 IHC, and baseline COX-2 expression. 66 subjects will be enrolled from the Amrita Institute for Medical Sciences over a 6-12 month period. All data management and biomarkers will be performed At MSKCC in New York except DNA ploidy, which will be measured at AIMS. After initial biopsy, subjects will be stratified for the presence of either early premalignant lesions (atypical hyperplasia, atypical hyperkeratosis, mild dysplasia) or advanced premalignant lesions (moderate or severe dysplasia or CIS). This will ensure equal distribution of high grade lesions into placebo and sulindac arms. Subjects will then be randomized to either sulindac 150 mg bid or placebo bid for six months. At the end of six months of treatment the lesion will be measured for the primary assessment of clinical efficacy, and biopsied for assessment of secondary endpoint biomarkers. Subjects will remain under observation for two additional months at which time the lesions will be measured and assessed for clinical change and biopsied for biomarker assessment. These final assessments can be compared to those at baseline and at 6 months to assess the durability of treatment effects. The study is powered to achieve an 80% chance of identifying a 30% response rate. The study is planned to accrue for 12 months and to be completed in 24 months. Not only will this study prove the feasibility of performing such trials but will also provide preliminary data for efficacy of COX inhibitors for tobacco related cancers, and for comparing biology of these lesions in India to those previously studied in the West. This high risk population will benefit from these advances.

描述（由申请人提供）： 拟议的试验是一项II期随机，双盲，安慰剂对照的化学预防试验试验，对150 mg BID Sulindac进行6个月的口服病变（OPL），持续6个月。目的是通过纽约的纪念斯隆 - 凯特林癌症中心（MSKCC）与印度喀拉拉邦的阿姆里塔医学科学研究所（AIMS）进行国际合作来确定进行此类研究的可行性。由于烟草暴露的习惯，该州的口腔癌和白细胞发病率最高。该研究还旨在确定Sulindac针对OPL的临床功效和安全性，并确定苏琳克对OPL组织中生物标志物的影响。生物标志物是DNA倍虫，Ki67 IHC，p53 IHC和基线COX-2表达。在6-12个月的时间内，将从阿姆里塔医学科学研究所（Amrita Medical Sciences）招收66名受试者。除DNA ploidy外，所有数据管理和生物标志物都将在纽约的MSKCC上进行，该数据将以AIMS进行测量。 初步活检后，将对患者进行早期预先病变（非典型增生，非典型高肿瘤性，轻度发育不良）或晚期预签名损伤（中度或重度发育不良或严重的发育异常或顺式）。这将确保高级病变的平等分布到安慰剂和苏莱达克臂。然后，受试者将被随机分为Sulindac 150 mg竞标或安慰剂出价六个月。在治疗六个月的结束时，将测量病变，以评估临床功效的主要评估，并进行活检以评估次要终点生物标志物。受试者将继续观察两个月，与临床变化进行测量并评估病变，并进行活检以进行生物标志物评估。可以将这些最终评估与基线时和6个月时的评估进行比较，以评估治疗效果的持久性。该研究有能力实现80％的机会识别30％的应答率。该研究计划累积12个月，并在24个月内完成。这项研究不仅可以证明执行此类试验的可行性，还将提供初步数据，以使COX抑制剂对烟草相关的癌症有效，并将这些病变的这些病变的生物学与先前在西方研究的人进行比较。这种高风险人群将从这些进步中受益。