Chemoprevention of Duodenal Polyps in FAP

描述(申请人提供)：这是一项II/11期研究，旨在评估Exisulind对十二指肠腺瘤性息肉的治疗效果，以及对接受过结肠切除术或可能接受过或可能没有接受过结肠切除术的家族性腺瘤性息肉病(FAP)患者的腺瘤和粘膜细胞凋亡的影响。这些受试者患十二指肠癌的遗传风险很高(相对风险为300)。这是一项双盲、安慰剂对照的单中心研究。将招收100名受试者，每支手臂50名。符合条件的受试者在一个测量的节段内有10到40个十二指肠息肉，随机接受Exisulind 150 mg口服。Qid或相同的安慰剂，为期一年。(患有AAPC的人如果结肠仍然完好无损，将在相同的时间内接受200 mg的出价。胃十二指肠镜检查将在基线上进行，以评估息肉状况，并在适用的情况下，在瓦特乳头上方10厘米处纹身。十二指肠息肉的数量和大小在基线和第一年的随访中被映射。将获得息肉和粘膜活检以进行细胞凋亡。每两个月联系受试者进行评估。药物每三个月分发一次，每月记录一次药片数量。在基线、1、3、6和12个月时进行化学、血细胞和尿液分析。所有有生育能力的女性最初都会接受β-HCG检查。NCI的共同毒性标准被用来检测毒性，外部数据安全监测委员会负责审查所有不良事件和任何协议问题。建议进行为期5年的研究。随机治疗周期为1年。将有6个月的终止阶段，包括数据分析、手稿准备和结束所有研究程序。

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.