Phase III Trial of Selenium for Prostate Cancer Prevention

描述(申请人提供)：营养预防癌症(NPC)试验是一项随机、双盲、口服硒(Se)补充的第三阶段临床干预试验，旨在测试Se对非黑色素瘤皮肤癌复发的预防化学作用。与安慰剂组相比，治疗组在最初10年的随访中观察到前列腺癌发病率显著降低了63%。对这项研究失明阶段最后三年的分析表明，在基线血浆硒水平最低的两个三分位数范围内，参与者的前列腺癌发病率显着下降。在这些组中，经过13年的随访，与安慰剂相比，治疗组的前列腺癌发病率分别降低了86%和67%。基于这些惊人的结果，这项建议的主要目标是继续并完成正在进行的随机、双盲、安慰剂对照的第三阶段临床试验(“阴性活检研究”，R01 CA77789)，旨在确定每日口服补硒作为一种化疗预防方案的安全性和有效性，这些患者被认为是前列腺癌的高风险男性，至少有一次前列腺癌活检阴性或高度上皮内瘤变(HGPIN)。这将使这项创新研究得以顺利完成，为目前正在研究的参与者提供持续和必要的后续行动，而不会中断补充和预定的评估。此外，前列腺癌的潜在预测生物标志物的调制将在从基线和随后的前列腺活检中收集的前列腺组织中进行分析。高硒酵母的安全性也将进一步建立。在这一竞争更新中继续检验的假设是，补充必要的微量元素硒将降低前列腺癌的发病率和相应的生物标记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，将为未来的血清蛋白质组学分析提供有价值的资源。免疫组织化学和前列腺活检组织中核染色质模式的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.