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，一项随机、双盲、口服硒（Se）补充的III期临床干预试验，在二次分析中显示，在治疗组最初10年的随访中，前列腺癌发病率降低了63%（1,2）。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（“观察等待研究”，U01 CA079080），以评估硒补充剂是否对诊断为前列腺癌的男性预防疾病进展有效。观察等待研究成功地随机分配了159名男性，他们有基线活检标本和重复血液样本（每3个月取一次）。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一个总体目标，因为男性非危及生命的疾病的治疗发病率很高。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。在没有更好的患者分化的情况下，伦理考虑排除了使用观察等待设置来改进治疗方案的机会。在缺乏诸如“观察等待研究”（Watchful Waiting Study）等早于当前护理标准的试验数据的情况下，几乎不可能测试硒补充剂作为降低临床模糊性疾病男性疾病复发风险的替代治疗的有效性。这项研究还提供了一个独特的机会，可以获得关于疾病自然进展的宝贵信息，这些信息在越来越难以研究的人群中得到。护理标准的变化迫使强调应计数转移到强调已登记患者的随访。对已经参加观察等待研究的参与者的继续随访提供了90%的能力来检测硒补充后PSA速度的31%的变化。因此，我们将有足够的权力来评估硒作为临床不确定疾病男性的替代药物，或者相反，证据表明，效果的幅度太小，可能会失去从目前的护理标准中获得的益处。

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.