ADJUVANT TRIAL WITH SOY AFTER RADICAL PROSTATECTOMY

描述（由申请人提供）：本项目的目的是完成一项正在进行的两组（n = 126/组）随机、双盲、安慰剂对照的I I/I 11期临床试验，该试验在根治性前列腺切除术后给予大豆蛋白分离物或基于酪蛋白的安慰剂长达两年的前列腺癌复发高危男性中进行。剂量为20 g蛋白质/天（~ 22 - 26 mg/天染料木黄酮和~ 38 - 42 mg/天总异黄酮）。初步结果表明，这种治疗是非常安全的。 在第1年每2个月和第2年每3个月用超灵敏测定法（其允许比常规测定法早一年检测PSA失效）测量血清PSA。我们将从美国各地至少8个临床研究中心共招募284名男性（根据初步结果，假设脱落率为13%），其中2个临床研究中心在VA医疗中心设有子研究中心。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。基于文献数据和已入选男性的特征，我们预计这组男性在两年内PSA失败率为30%，这些男性必须满足以下资格标准中的至少一个：术前PSA >20 ng/ml，Gleason总和> 7，手术切缘阳性，囊外扩张，精囊浸润和/或淋巴结（微）转移。126/组的样本量将使我们能够检测到PSA失败率从30%降低40%至18%，在显著性水平为0.05时具有80%的功效。我们还将确定大豆干预是否影响PSA失败时间、血清胆固醇和血清甘油三酯水平。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（甲状腺活性）的影响。这项研究将产生有关大豆蛋白的能力，含有异黄酮，以防止前列腺癌根治术后复发的信息。该研究还将提供关于大豆蛋白在未被诊断患有前列腺癌的男性中的预防潜力的信息，因为这些男性中未被检测到的组织学前列腺癌的患病率很高（>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.