Phase III Trial of Selenium for Prostate Cancer Prevention

硒预防前列腺癌的 III 期试验

• 批准号: 7414720
• 负责人: Frederick R Ahmann
• 金额: $ 58.81万
• 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/7414720
• 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（由申请人提供）：癌症营养预防 (NPC) 试验是一项随机、双盲、口服硒 (Se) 补充剂的 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 10 年的随访中，与安慰剂组相比，治疗组的前列腺癌发病率显着降低了 63%。对本研究盲法阶段最后三年的分析表明，基线血浆硒水平最低两个三分位数内的参与者的前列腺癌发病率显着下降。在这些组中，13 年随访后，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，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 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的安全性和有效性，用于被认为是前列腺癌高危且至少一次前列腺活检呈阴性的男性。 癌症或高级上皮内瘤变 (HGPIN)。这将为当前研究的参与者提供持续和必要的随访，从而成功完成这项创新研究，而不会中断补充和预定的评估。此外，将从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。在这场竞争更新中继续检验的假设是，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生物标志物的表达。主要终点是随后前列腺活检中前列腺癌的发生率。本研究期间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分析提供宝贵的资源。 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。