Phase III Trial of Selenium for Prostate Cancer Prevention

描述（由申请人提供）：营养预防癌症（NPC）试验是一项随机、双盲、口服补充硒（Se）的III期临床干预试验，旨在测试硒对非黑色素瘤皮肤癌复发的预防化疗作用。在最初的10年随访中，治疗组与安慰剂组相比，前列腺癌发病率显著降低63%。对该研究最后三年的盲法阶段的分析显示，在基线血浆硒水平最低的两分位数的参与者中，前列腺癌发病率显著降低。在这些组中，经过13年的随访，治疗组与安慰剂组的前列腺癌发病率分别下降了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一项正在进行的随机、双盲、安慰剂对照的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一种化疗预防方案的安全性和有效性，该方案适用于至少一次前列腺活检阴性的前列腺癌或高级别上皮内瘤变（HGPIN）的前列腺癌高危男性。这将为目前正在研究的参与者提供持续和必要的随访，而不会中断补充和预定的评估，从而使这项创新研究顺利完成。此外，将在基线和随后的前列腺活检收集的前列腺组织中分析前列腺癌潜在预测性生物标志物的调节。高硒酵母的安全性也将进一步确定。在这个竞争性的更新中，继续测试的假设是补充必需微量元素硒将降低前列腺癌的发病率和相应的生物标志物在高危男性中的表达。主要终点是前列腺癌在随后的前列腺活检中的发病率。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宝贵的资源。前列腺活检组织的免疫组织化学和核染色质模式分析将作为前列腺癌的中间终点生物标志物进行研究。

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.