Improving Quality of Life of Prostate Cancer Survivors with Androgen Deficiency

改善雄激素缺乏的前列腺癌幸存者的生活质量

• 批准号: 9918241
• 负责人: SHALENDER BHASIN
• 金额: $ 75.47万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918241
• 关键词: Adverse event; Advocate; Aerobic; Affect; Affective; American; Androgens; Area; Attention; Biochemical; Cardiovascular system; Clinical Trials Data Monitoring Committees; Complex; Data; Diagnosis; Disease; Distress; Double-Blind Method; Elements; Enrollment; Equilibrium; Evaluation; Fatigue; Fright; Functional disorder; Gel; Gene Expression; Gleason Grade for Prostate Cancer; Growth; Hematocrit procedure; High Prevalence; Letters; Lipids; Localized Disease; Malignant Neoplasms; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Monitor; Moods; Oncologist; Oncology Group; Organ; Participant; Patient Self-Report; Patients; Personal Satisfaction; Physical Function; Placebos; Population; Prostate; Prostate specific antigen measurement; Published Comment; Quality of life; Radical Prostatectomy; Randomized; Recommendation; Recurrence; Reporting; Research; Risk; Safety; Sex Behavior; Sex Functioning; Sexual Dysfunction; Specific qualifier value; Structure; Subjects Selections; Survivors; Symptoms; Testosterone; Urologist; VO2max; androgen sensitive; deprivation; disorder risk; editorial; efficacy trial; epidemiology study; feasibility trial; health related quality of life; improved; instrument; lean body mass; men; multidisciplinary; muscle form; muscle strength; open label; patient population; performance based measurement; prostate cancer risk; prostate cancer survivors; randomized trial; risk minimization; survivorship; symptom treatment; symptomatic improvement; testosterone replacement therapy; trial design

SUMMARY Substantial improvement in survival in men with prostate cancer (PCa) has focused attention on the high prevalence of sexual dysfunction, physical dysfunction, and low energy, which are important contributors to suboptimal health-related quality of life (HRQOL) in prostate cancer survivors. The pathophysiology of these symptoms in prostate cancer survivors is multifactorial, but androgen deficiency is a frequent, remediable contributor. In healthy hypogonadal men, testosterone replacement therapy (TRT) improves these symptoms, suggesting that it also might do so for survivors of PCa who have testosterone deficiency. However, because testosterone promotes the growth of metastatic prostate cancer, there has been concern about administering TRT to prostate cancer survivors. Open label trials and retrospective analyses have reported very low recurrence rates in men who have undergone radical prostatectomy and received TRT, but neither safety nor efficacy have been evaluated in a randomized trial in this population. The South West Oncology Group patient advocates have deemed this a high priority question for prostate cancer survivors. Our primary aim is to conduct a double-blind, placebo-controlled, parallel-group, randomized trial to determine whether testosterone replacement is safe and efficacious in improving sexual function in men with androgen deficiency, who have undergone radical prostatectomy for pT2,N0,M0, Gleason score ≤6 disease and are at very low risk of disease recurrence. A secondary aim is to determine whether TRT improves muscle mass and strength, and self reported and performance-based measures of physical function. The third objective is to determine the effects of TRT on wellbeing and affect, mood, energy, and quality of life. The trial will enroll men, 40 years or older, who have undergone radical prostatectomy for organ-localized prostate cancer (pT2,N0,M0); with Gleason score ≤6; pre-treatment PSA <10 ng/mL; and undetectable PSA (<0.1 ng/mL) for at least two years after radical prostatectomy; who have symptoms of sexual dysfunction, fatigue, or physical dysfunction; and who have unequivocally low total (average of two morning levels <275 ng/dL) or free testosterone (<60 pg/mL) levels. Participants will be randomized to receive placebo or testosterone gel for 12 weeks. Changes in sexual activity, sexual desire, erectile function, sexual distress, sexual life quality, lean body mass, muscle strength, physical function, affectivity balance, and energy will be evaluated at baseline, 6 and 12 weeks. We will monitor hematocrit, PSA, and biochemical recurrence, defined as” PSA of ≥0.2 ng/mL with a confirmatory level of ≥0.2 ng/mL”. Careful selection of subjects with very low risk of recurrence, rigorous safety monitoring, pre-specified stopping rules, and oversight by an independent DSMB will minimize risks. Extensive preliminary data support the feasibility of this trial. Randomized trial design, a multidisciplinary team, careful attention to statistical power, and selection of symptomatic men with unequivocally low testosterone will insure the validity of the assessment of efficacy and safety of testosterone therapy in this needy patient population.

概括 前列腺癌 (PCa) 男性生存率的显着改善引起了人们的关注 性功能障碍、身体功能障碍和精力不足的普遍存在，这些都是导致 前列腺癌幸存者的健康相关生活质量 (HRQOL) 不理想。这些疾病的病理生理学 前列腺癌幸存者的症状是多因素的，但雄激素缺乏是常见的、可治愈的 贡献者。在健康的性腺功能减退男性中，睾酮替代疗法（TRT）可以改善这些症状， 这表明它也可能对患有睾酮缺乏的 PCa 幸存者产生作用。然而，因为 睾酮促进转移性前列腺癌的生长，但人们一直担心服用睾酮 对前列腺癌幸存者进行 TRT。开放标签试验和回顾性分析报告的数据非常低 接受根治性前列腺切除术并接受 TRT 的男性的复发率，但安全性和 疗效已在该人群中的一项随机试验中得到评估。西南肿瘤学组患者 倡导者认为这是前列腺癌幸存者的一个高度优先的问题。 我们的主要目标是进行双盲、安慰剂对照、平行组随机试验，以确定 睾酮替代疗法对于改善雄激素男性的性功能是否安全有效 因 pT2、N0、M0、格里森评分≤6 分疾病接受根治性前列腺切除术且处于 疾病复发的风险非常低。第二个目标是确定 TRT 是否可以改善肌肉质量和 力量、自我报告和基于表现的身体机能测量。第三个目标是 确定 TRT 对健康和情感、情绪、能量和生活质量的影响。该试验将招募男性， 40岁或以上，因器官局限性前列腺癌接受根治性前列腺切除术（pT2，N0，M0）； 格里森评分≤6；治疗前 PSA <10 ng/mL；且至少两次检测不到 PSA (<0.1 ng/mL) 根治性前列腺切除术后数年；有性功能障碍、疲劳或身体功能障碍症状的人； 总睾酮水平（两个早晨的平均值 <275 ng/dL）或游离睾酮水平（<60 pg/mL）水平。参与者将随机接受安慰剂或睾酮凝胶治疗，为期 12 周。变化 性活动、性欲、勃起功能、性困扰、性生活质量、去脂体重、肌肉 将在基线、第 6 周和第 12 周评估力量、身体机能、情感平衡和能量。我们 将监测血细胞比容、PSA 和生化复发，定义为“PSA ≥0.2 ng/mL，并具有确认性 水平≥0.2 ng/mL”。精心挑选复发风险极低的受试者，严格的安全监测， 预先指定的停止规则以及独立 DSMB 的监督将最大限度地降低风险。广泛的初步 数据支持了本次试验的可行性。随机试验设计，多学科团队，细心关注 统计功效，并选择有明显低睾酮水平的有症状男性将确保有效性 评估睾酮治疗在这一贫困患者群体中的疗效和安全性。