Phase III Trial of Selenium for Prostate Cancer Prevention

硒预防前列腺癌的 III 期试验

• 批准号: 7236577
• 负责人: Frederick R Ahmann
• 金额: $ 60.54万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7236577
• 关键词: Affect; Apoptosis; Binding Proteins; Biological Markers; Biopsy; Biopsy Specimen; Blinded; Cancer Prevention Trial; Chromatin; Clinical; Coenzyme A; Daily; Development; Diagnosis; Disease; Disruption; Dose; Double-Blind Method; Employee Strikes; End Point; Enrollment; Future; Immunohistochemistry; Incidence; Informed Consent; Intervention Trial; Intraepithelial Neoplasia; Karyometry; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; N-Cadherin; Nuclear; Nutritional; Oral; Oral cavity; Paraffin Embedding; Participant; Patients; Pattern; Phase; Phase III Clinical Trials; Placebo Control; Placebos; Plasma; Predictive Value; Preventive; Proliferation Marker; Prostate; Prostate-Specific Antigen; Proteins; Proteomics; Racemases; Randomized; Recurrence; Resources; Risk; Safety; Sampling; Schedule; Selenium; Serum; Skin Carcinoma; Supplementation; TP53 gene; Testing; Tissues; Trace Elements; Treatment Protocols; Yeasts; base; calmodulin-dependent protein kinase III; design; follow-up; high risk men; innovation; men; prostate cancer prevention; response; tumor

DESCRIPTION (provided by applicant): The Nutritional Prevention of Cancer (NPC) Trial, a randomized, double-blind, Phase III clinical intervention trial of oral selenium (Se) supplementation, was designed to test the preventive chemo effects of Se on recurrence of non-melanoma skin cancer. A striking 63% reduction in prostate cancer incidence during the initial 10 years of follow- up was observed in the treatment group compared to the placebo group. An analysis of the last three years of the blinded phase of this study showed a significant decrease in prostate cancer incidence in participants within the lowest two tertiles of baseline plasma selenium levels. In these groups, the prostate cancer incidence after 13 years of follow-up was decreased by 86% and 67%, respectively, in the treatment group vs. placebo. Based on these striking results, the primary objective of this proposal is to continue and complete an ongoing randomized, double-blind, placebo-controlled Phase III clinical trial (the "Negative Biopsy Study", R01 CA77789), designed to determine the safety and efficacy of daily oral Se supplementation as a chemo preventive regimen in men considered to be at high-risk for prostate cancer who have had at least one prostate biopsy negative for cancer or high-grade intraepithelial neoplasia (HGPIN). This will allow successful completion of this innovative study by providing continuous and necessary follow-up of participants currently on study, without disruption of supplementation and scheduled assessments. In addition, modulation of potentially predictive biomarkers of prostate cancer will be analyzed in prostate tissue collected from baseline and subsequent prostate biopsies. The safety profile of high-selenium yeast will also be further established. The hypothesis continuing to be tested in this competing renewal is that supplementation with the essential trace element selenium will decrease the incidence of prostate cancer and corresponding biomarker expression in high-risk men. The primary endpoint is the incidence of prostate cancer on subsequent prostate biopsy. Serum samples collected during this study are used to analyze serum prostate specific antigen (PSA) levels, and will provide a valuable resource for future serum proteomic analyses. Immunohistochemistry and analyses of nuclear chromatin patterns in prostate biopsy tissue will be studied as intermediate endpoint biomarkers of prostate cancer.

描述（申请人提供）：营养预防癌症（NPC）试验是一项口服硒（Se）补充剂的随机、双盲、III期临床干预试验，旨在测试Se对非黑色素瘤皮肤癌复发的预防性化疗作用。与安慰剂组相比，在最初10年的随访中，治疗组的前列腺癌发病率显著降低了63%。对本研究盲态阶段最后三年的分析显示，基线血浆硒水平最低两个三分位数内的参与者前列腺癌发病率显著降低。在这些组中，治疗组与安慰剂组相比，13年随访后前列腺癌发病率分别降低了86%和67%。基于这些惊人的结果，本提案的主要目标是继续并完成正在进行的随机、双盲、安慰剂对照III期临床试验（“阴性活检研究”，R01 CA77789），旨在确定每日口服硒补充剂作为化疗预防方案在被认为处于高血糖的男性中的安全性和有效性。至少有一次前列腺活检阴性的癌症或高级别上皮内瘤变（HGPIN）的前列腺癌风险。这将通过对目前正在研究的受试者进行持续和必要的随访，在不中断补充和计划评估的情况下，成功完成这项创新性研究。此外，将在从基线和后续前列腺活检收集的前列腺组织中分析前列腺癌的潜在预测生物标志物的调节。 高硒酵母的安全性也将进一步建立。在这一竞争性更新中继续测试的假设是，补充必需微量元素硒将降低高危男性前列腺癌的发病率和相应的生物标志物表达。主要终点是随后的前列腺活检中前列腺癌的发生率。本研究收集的血清样本用于分析血清前列腺特异性抗原（PSA）水平，并将为未来的血清蛋白质组学分析提供有价值的资源。 将研究前列腺活检组织中的免疫组织化学和核染色质模式分析，作为前列腺癌的中间终点生物标志物。