Phase II Chemoprevention Trial of Selenium and Prostate Cancer

描述(由申请人提供)：营养预防癌症(NPC)试验是一项随机、双盲、口服硒(Se)补充的第三阶段临床干预试验，经二次分析表明，在治疗组(1，2)的最初10年随访中，前列腺癌发病率降低了63%。基于这些结果和我们自己的研究，我们启动了一项随机、双盲、安慰剂对照的LLB期临床试验(“Watchful Waiting Study”，U01 CA079080)，以评估补充Se在预防前列腺癌男性患者疾病进展方面是否有效。这项观察等待研究成功地随机选择了159名有基线活组织检查样本和重复血液样本(每3个月采集一次)的男性。确定疾病特征和/或血液生物标志物对治疗计划具有更大的预测价值仍然是首要目标，因为在患有非危及生命的疾病的男性中，治疗发病率很高。然而，在目前推荐的护理标准下，很少有男性放弃治疗他们的疾病。在没有更好的患者区分的情况下，伦理考虑排除了使用警惕的等待设置来改善治疗方案的机会。在缺乏像《观察等待研究》这样早于当前护理标准的试验数据的情况下，几乎不可能测试补充硒作为一种替代疗法的有效性，以降低患有临床不明确疾病的男性的疾病复发风险。这项研究还提供了一个独一无二的机会，可以获得关于疾病自然发展的宝贵信息，在一个变得非常难以研究的人群中。护理标准的变化迫使对应计费用的重视转向对已经登记的患者的随访。继续对已经在观察等待研究中的参与者进行随访，可以提供90%的能力来检测补充硒后PSA速度31%的变化。因此，我们将有足够的能力评估Se作为临床上不确定的疾病男性的替代制剂，或者相反，证据表明其影响的幅度太小，不可能失去从当前护理标准中获得的好处。 在这次更新中，我们建议完成对那些已经登记并继续选择放弃治疗的男性的数据收集，方法是对目前正在研究的参与者进行持续和必要的跟踪，而不中断补充和预定的评估，以完成终点数据的确定，以测试补充硒在延迟或预防前列腺癌方面的效果。这项研究的主要目的是测试补充Se对PSA速度测量的疾病进展的影响。其次，凭借其独特的生物样品资源，这项研究足以测试几个重要的次要问题，即基线组织生物标记物的表达和血清蛋白质/蛋白质谱作为疾病进展和对补硒反应的独立决定因素的作用。

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 showed, on secondary analysis, a 63% reduction in prostate cancer incidence during the initial 10 years of follow up in the treatment arm (1,2). Based on these results and our own studies, we initiated a randomized, double-blind, placebo-controlled Phase llb clinical trial (the "Watchful Waiting Study", U01 CA079080) to assess whether Se supplementation has efficacy in preventing disease progression in men diagnosed with prostate cancer. The Watchful Waiting Study successfully randomized 159 men for whom baseline biopsy specimens are available as well as repeat blood samples (taken every 3 months). It remains an overarching goal to identify disease characteristics and/or blood biomarkers with greater predictive value for treatment planning because of the high treatment morbidity among men with non-life threatening disease. However with the current recommended standard of care, few men forego treatment for their disease. In the absence of better patient differentiation, ethical considerations preclude opportunity to improve upon treatment options using a watchful waiting setting. In the absence of data from trials such as the "Watchful Waiting Study" that predate the current standard of care, it will be near impossible to test the efficacy of Se supplementation as an alternative treatment for reducing risk of disease recurrence for men with clinically ambiguous disease. This study also provides an exclusive opportunity to obtain invaluable information on the natural progression of disease in a population that is getting exceedingly difficult to study. Changes in the standard of care forced the emphasis on accrual to shift to an emphasis on follow-up of patients already enrolled. Continuation of follow-up of participants already in the Watchful Waiting Study affords 90% power to detect a 31% change in PSA velocity with Se supplementation. Thus, we will have adequate power to evaluate Se as an alternative agent for men with clinically indeterminate disease or conversely, evidence that the magnitude of effect is too marginal to risk losing the benefit gained from the current standard of care. In this renewal, we propose to complete data collection on those men already enrolled, who continue to choose to forego treatment, by providing continuous and necessary follow-up of participants currently on study, without interruption of supplementation and scheduled assessments to complete the ascertainment of endpoint data to test the efficacy of Se supplementation in delaying or preventing prostate cancer. The primary objective of this study is to test the effect of Se supplementation on disease progression measured by PSA velocity. Secondary to this objective, with its unique biospecimen resource, this study is adequately powered to test several important secondary questions about the role of baseline tissue biomarker expression and serum protein/protein profiles as independent determinants of disease progression and responsiveness to Se supplementation.