Phase II Chemoprevention Trial of Selenium and Prostate Cancer

硒与前列腺癌的 II 期化学预防试验

• 批准号: 7048206
• 负责人: Frederick R Ahmann
• 金额: $ 49.03万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048206
• 关键词: biomarker; blood proteins; chemoprevention; chromatin; clinical research; clinical trial phase II; drug screening /evaluation; gene expression; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; patient oriented research; prostate neoplasms; prostate specific antigen; selenium

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.

描述（由申请人提供）：营养预防癌症（NPC）试验，一项口服硒（Se）补充剂的随机、双盲、III期临床干预试验，在二次分析中显示，治疗组在最初10年随访期间前列腺癌发病率降低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IIb期临床试验（“观察等待研究”，U 01 CA 079080），以评估硒补充剂是否有效预防诊断为前列腺癌的男性疾病进展。观察等待研究成功地随机分配了159名男性，他们的基线活检标本以及重复血液样本（每3个月采集一次）。由于患有非危及生命疾病的男性的治疗发病率较高，因此确定对治疗计划具有更大预测价值的疾病特征和/或血液生物标志物仍然是一个首要目标。然而，根据目前推荐的护理标准，很少有男性放弃治疗他们的疾病。在缺乏更好的患者区分的情况下，伦理考虑排除了使用观察等待设置来改进治疗选择的机会。在缺乏数据的试验，如“观察等待研究”，早于目前的护理标准，这将是几乎不可能测试的疗效，硒补充剂作为一种替代治疗，以减少疾病复发的风险，为男性与临床模棱两可的疾病。这项研究还提供了一个独家的机会，以获得宝贵的信息，疾病的自然进展，在人口越来越难以研究。护理标准的变化迫使重点从应计转移到对已入组患者的随访。继续随访观察等待研究中的参与者提供了90%的把握度来检测补硒后PSA速度的31%变化。因此，我们将有足够的能力来评估硒作为临床不确定疾病的男性的替代药物，或者相反，有证据表明效果的程度太小，不会有失去从当前标准治疗中获得的获益的风险。 在本次更新中，我们建议通过对目前正在研究的参与者进行连续和必要的随访，完成对那些已经入组但继续选择放弃治疗的男性的数据收集，而不中断补充和计划的评估，以完成终点数据的确定，以测试硒补充剂在延迟或预防前列腺癌方面的疗效。本研究的主要目的是测试补硒对PSA速度测量的疾病进展的影响。其次，这一目标，其独特的生物标本资源，这项研究有足够的动力来测试几个重要的次要问题的作用，基线组织生物标志物的表达和血清蛋白质/蛋白质谱作为疾病进展的独立决定因素和对补硒的反应。