Phase III Study of the Effects of Selenium on Adenomas

硒对腺瘤影响的三期研究

• 批准号: 6986606
• 负责人: M. Peter Lance
• 金额: $ 145.49万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986606
• 关键词: adenomatous polyps; cancer prevention; chemoprevention; clinical research; clinical trial phase III; colon surgery; colorectal neoplasms; combination chemotherapy; cyclooxygenase inhibitors; dietary supplements; drug interactions; drug screening /evaluation; endoscopy; gastrointestinal imaging /visualization; human subject; human therapy evaluation; longitudinal human study; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; nonsteroidal antiinflammatory agent; oxidoreductase inhibitor; patient oriented research; pharmacogenetics; selenium; single nucleotide polymorphism

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Colorectal adenomas (CRAs) are the precursors of CRCs, but most CRAs do not progress to CRCs. Advanced CRAs, those CRAs most likely to progress, are highlighted in this Colon Cancer Prevention Program Project (CCPPP). Most CRAs are amenable to endoscopic polypectomy. Recurrent CRAs develop at a rate of 10-15% per year in patients with previous CRAs and serve as endpoints in CRC chemoprevention trials. CRA recurrence trials of a wheat bran fiber (WBF) supplement and ursodeoxychclic acid (UDCA) were completed in earlier CCPPP grants. The current is a placebo-controlled factorial-design, CRA recurrence trial of celecoxib and selenium (Cel/Sel), administered individually and together, to 1600 participants after a recent CRA polypectomy. Celecoxib, a selective cyclooxygenase (COX)- 2 inhibitor, is hypothesized to have less toxicity than aspirin with equivalent anti-neop!astic efficacy. Selenium supplementation has been shown to protect against CRC and prevalent CRAs as secondary but not primary trial endpoints. Cel/Sel randomization is stratified for concomitant low-dose aspirin (<81 mg daily) therapy RA recurrence rates by intervention group will be determined at endpoint colonoscopies performed 3 to 5 years after baseline. Cel/Sel randomization will be completed by early 2006. Resources, including hose from the WBF and UDCA trials, are essential for the conduct of CCPPP; they include clinical and risk factor data, baseline and recurrent CRA tissue, and archived plasma and DNA. By the completion of randomization of Cel/Sel trial participants in early 2006, baseline data from = 4,300 CRA patients will be available. In addition to individual effects of celecoxib and selenium, exploratory analyses of their nteraction will be conducted. As secondary objectives, the influence of single nucleotide polymorphism variations will be analyzed in six genes for which there is evidence of genotypic effect modification of the celecoxib, aspirin or selenium interventions, or their toxicities: ornithine decarboxylase, cytochrome P450 209. UDP-glucuronosyltransferase 1A6 and the GPx-1, GPx-2 and Sep15 selenoprotein genes.

结直肠癌(CRC)是美国癌症死亡的第二大原因。结直肠腺瘤是结直肠癌的前驱疾病，但大多数结直肠腺瘤不会进展为结直肠癌。晚期CRA，即最有可能进展的CRA，在本结肠癌预防计划项目(CCPPP)中得到强调。大多数CRA可以接受内窥镜息肉切除术。在既往有CRA的患者中，复发的CRA以每年10-15%的速度发展，并作为CRC化学预防试验的终点。一种小麦麸皮纤维(WBF)补充剂和熊去氧环酸(UDCA)的CRA重复试验在CCPPP的早期拨款中完成。目前的研究是一项安慰剂对照析因设计，塞来昔布和硒的CRA复发试验(CEL/SEL)，分别和联合使用，参加最近CRA息肉切除术的1600名参与者。塞来昔布是一种选择性环氧合酶(COX)-2抑制剂，据推测其毒性低于阿司匹林，具有同等的抗肿瘤疗效。补硒已被证明是次要的，但不是主要的，可以预防结直肠癌和常见的CRA 试验终点。CEL/SEL随机分组配合小剂量阿司匹林(每天81毫克)治疗RA，干预组的RA复发率将在基线后3至5年内进行结肠镜检查时确定。CEL/SEL随机化将于2006年初完成。资源，包括来自WBF和UDCA试验的软管，对于开展CCPPP是必不可少的；它们包括临床和危险因素数据、基线和复发的CRA组织以及存档的血浆和DNA。到2006年初CEL/SEL试验参与者的随机化完成时，将有=4300名CRA患者的基线数据。除了塞来昔布和硒的单独作用外，还将对它们的相互作用进行探索性分析。作为次要目标，单核苷酸多态变异的影响将在六个基因中进行分析，这些基因有证据表明基因类型效应改变。 塞来昔布、阿司匹林或硒干预或其毒性：鸟氨酸脱羧酶，细胞色素P450 209。UDP-葡萄糖醛酸基转移酶1A6和GPX-1、GPX-2和Sep15硒蛋白基因。