Chemoprevention of Duodenal Polyps in FAP

描述（由申请人提供）：这是一项II/III期研究，旨在评价依昔舒林治疗已行结肠切除术的家族性腺瘤性息肉病（FAP）患者或可能已行或未行结肠切除术的减毒腺瘤性结肠息肉病（AAPC）患者的十二指肠腺瘤性息肉以及腺瘤和粘膜细胞凋亡测定的效果。这些受试者具有确定的发生十二指肠癌的高遗传风险（相对风险300）。这是一项双盲、安慰剂对照、单中心研究。将入组100例受试者，每组50例。将在测量段内具有10至40个十二指肠息肉的合格受试者随机接受依昔舒林150 mg p.o. qid或相同的安慰剂，持续一年。（仍有结肠完整的AAPC患者将在相同的持续时间内接受200 mg bid。将在基线时进行胃镜检查，以评估息肉状态，并在适用的情况下，在乏特乳头外10 cm处进行纹身。十二指肠息肉的数量和大小在基线和第一年随访时进行了映射。将获得息肉和粘膜活检用于细胞凋亡。每两个月联系一次受试者进行评估。每三个月分发一次药物，每月记录一次药丸数量。在基线和1、3、6和12个月时进行化学、CBC和尿分析。首先对所有有生育能力的妇女进行β-HCG检查。采用NCI常见毒性标准检测毒性，外部数据安全性监测委员会负责审查所有不良事件和任何方案问题。建议进行为期5年的研究。随机治疗期为1年。将有一个6个月的终止阶段，包括数据分析、手稿准备和所有研究程序的关闭。

DESCRIPTION (provided by applicant): This is a Phase II/lll study to evaluate the effects of exisulind for treatment on duodenal adenomatous polyps and on adenoma and mucosal apoptosis assays in Familial Adenomatous Polyposis (FAP) patients who have had colectomy or Attenuated Adenomatous Polyposis Coli (AAPC) patients whom may or may not have undergone colectomy. These subjects have a defined high genetic risk of developing duodenal cancer (relative risk 300). This is a double blind, placebo controlled, single center study. One hundred subjects, fifty each arm, will be enrolled. Eligible subjects who harbor 10 to 40 duodenal polyps within a measured segment are randomized to receive exisulind 150 mg p.o. qid or an identical placebo for the duration of one year. (Persons with AAPC whom still have colon intact will receive 200 mg bid for the same duration. Gastroduodenoscopy will be performed at baseline to assess polyp status and place, where applicable, a tattoo 10 cm beyond the papilla of Vater. Duodenal polyps are mapped for number and size at baseline and at follow up at year one. Polyp and mucosal biopsies will be obtained for apoptosis. Subjects are contacted bi-monthly for assessments. Drug is dispensed every three months and a pill count is recorded monthly. Chemistries, CBC and urinalysis is performed at baseline and at 1, 3, 6 and 12 months. A beta-HCG is performed initially on all fertile women. The NCI common toxicity criteria is employed to detect toxicities and an external Data Safety Monitoring Committee serves to review all adverse events and any protocol issues. A 5-year study is proposed. The randomized treatment period is 1 year. There will be a 6 month termination phase to include data analysis, manuscript preparation and closure of all study procedures.