ADJUVANT TRIAL WITH SOY AFTER RADICAL PROSTATECTOMY

描述(申请人提供)：该项目的目标是完成一项正在进行的两个ARM(n=126/ARM)随机、双盲、安慰剂对照的I/I 11期临床试验，对象是前列腺癌根治性切除术后复发风险高的男性，服用大豆分离蛋白或酪蛋白安慰剂长达两年。剂量为20g蛋白质/天(-22-26毫克/天金雀异黄素和-38-42毫克/天总异黄酮)。初步结果表明，这种治疗是非常安全的。第一年的每两个月和第二年的每三个月，我们将用一种超灵敏的分析方法(这种方法可以比常规分析提前一年检测到PSA失败)来检测血清PSA。我们将从美国至少八个临床地点招募284名男性(根据初步结果，假设辍学率为13%)，其中两个临床地点也在退伍军人医学中心设有子站点。比较治疗组和安慰剂组，主要终点是PSA失败率，作为前列腺癌复发的替代指标。根据文献数据和已经登记的男性的特征，我们预计在这组必须满足以下至少一项资格标准的男性中，两年内PSA失败率为30%：术前PSA和GT；20 ng/ml，Gleason和&gt；7，手术切缘阳性，包膜外侵犯，精囊侵犯，和/或淋巴结(微)转移。126个/ARM的样本量将使我们在0.05的显著水平上检测到PSA故障率从30%降低到18%，功率为80%。我们还将确定大豆干预是否会影响PSA失败的时间、血清胆固醇和血清异黄酮水平。此外，还将确定对睾酮、雌二醇和SHBG(类固醇激素轴)以及T3和T4(甲状腺活动)的影响。这项研究将提供有关含有异黄酮的大豆蛋白预防前列腺癌根治术后复发的能力的信息。这项研究还将提供有关大豆蛋白在未被诊断为前列腺癌的男性中的预防潜力的信息，因为在这些男性中，未被发现的组织学前列腺癌的患病率很高(&gt；50%)。

DESCRIPTION (provided by applicant): The objective of this project is to complete an ongoing two arm (n = 126/arm) randomized, double-blind, placebo-controlled phase I I/I 11 clinical trial in men who are at high risk for prostate cancer recurrence after a radical prostatectomy with administration of soy protein isolate or a casein-based placebo for up to two years. The dose is 20 g protein/day (-22-26 mg/day genistein and -38-42 mg/day total isoflavones). Preliminary results indicate that this treatment is extremely safe. Serum PSA is being measured with an ultra- sensitive assay (which allows detection of PSA failure one year earlier than conventional assays) every 2 months in year 1 and every 3 months in year 2. We will accrue a total of 284 men (assuming a 13% drop-out rate based on preliminary results) from at least eight clinical sites around the USA, two of which also have a sub-site at a VA Medical Center. Comparing the treatment and placebo groups, the primary end-point is the rate of PSA failure as surrogate for prostate cancer recurrence. Based on literature data and the characteristics of already enrolled men, we expect a 30% rate of PSA failure in two years in this group of men who must fulfill at least one of the following eligibility criteria: pre-operative PSA >20 ng/ml, Gleason sum of > 7, positive surgical margins, extracapsular extension, seminal vesicle invasion, and/or lymph node (micro) metastases. The sample size of 126/arm will allow us to detect a 40% reduction in the rate of PSA failure from 30% to 18% with 80% power at a significance level of 0.05. We will also determine whether the soy intervention affects time-to-PSA failure, serum cholesterol, and serum isoflavone levels. In addition, effects will be determined on testosterone, estradiol, and SHBG (steroid hormone axis), and T3 and T4 (thyroid activity). This study will yield information about ability of soy protein containing isoflavones to prevent recurrence of prostate cancer after radical prostatectomy. The study will also provide information about the preventive potential of soy protein in men that have not been diagnosed with prostate cancer, because there is a high prevalence (>50%) in these men of undetected histologic prostate carcinomas.