A Randomized Phase II Trial of Flibanserin in Men Receiving Androgen Suppression for Prostate Cancer

氟班色林在接受雄激素抑制治疗前列腺癌的男性中的随机 II 期试验

• 批准号: 10195766
• 负责人: Andrew M McDonald
• 金额: $ 20.83万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-19 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10195766
• 关键词: Adverse effects; Adverse event; Aggressive behavior; Agonist; Alabama; Androgen Suppression; Androgens; Behavior; Behavioral; Biochemical; Brain; Brain region; Cancer Intervention; Cancer Survivorship; Castration; Client satisfaction; Clinical; Clinical Trials; Coitus; Comprehensive Cancer Center; Diagnosis; Disadvantaged; Distress; Dopamine; Dopamine Agonists; Dopamine D2 Receptor; Double-Blind Method; Drug Interactions; Equilibrium; Erectile dysfunction; Ergot Fungus; Estrogens; Evidence based treatment; Exercise; Female; Frequencies; Goals; Gynecomastia; Human; Hyperprolactinemia; Hypoactive Sexual Desire Disorder; Intervention; Life; Life Style; Localized Disease; Malignant neoplasm of prostate; Morbidity - disease rate; Neurotransmitters; Participant; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Phase II Clinical Trials; Phase II/III Trial; Phase III Clinical Trials; Placebos; Premenopause; Prostate Cancer therapy; Psychoses; Quality of life; Radiation; Randomized; Rattus; Reporting; Research; Research Personnel; Risk; Safety; Serotonin; Serotonin Agonists; Sex Behavior; Sex Functioning; Sexual Dysfunction; Sexual Health; Site; Specific qualifier value; Spouses; Structure; Synapses; Testosterone; Thromboembolism; Time; Toxic effect; United States; Universities; Well in self; Woman; androgen deprivation therapy; arm; cabergoline; cardiovascular effects; design; experience; flibanserin; high risk; improved; inhibitor/antagonist; interest; male; men; multidisciplinary; negative affect; neurochemistry; phase II trial; phosphodiesterase V; placebo group; preclinical study; preservation; prostate cancer survivors; psychologic; receptor; recruit; sex; success; treatment strategy

PROJECT SUMMARY Androgen deprivation therapy (ADT) is used to improve survival for men with metastatic and high risk localized prostate cancer. Unfortunately, ADT is also associated with a number of adverse effects, and sexual dysfunction occurs in nearly all men who receive this treatment. Sexual dysfunction is the most common complaint among men with prostate cancer and contributes to worse quality of life (QoL). The loss of sexual interest, in particular, is highly distressing for men with prostate cancer and their partners, which contributes additional psychological morbidity in these patients. Despite the importance of sexual health in men with prostate cancer, previous interventions to improve sexual interest in men receiving ADT have had little success, and new strategies are needed. We hypothesize that flibanserin can be used to increase sexual desire among men receiving ADT for prostate cancer. Flibanserin is a multifunctional serotonin receptor agonist/antagonist that acts as an agonist of post-synaptic 5-HT(1A) receptors and an antagonist of 5-HT(2A) receptors, that has previously been approved to treat hypoactive sexual desire disorder in women. In this proposal, we will conduct a double blind, placebo controlled, randomized phase II clinical trial to assess the efficacy and safety of flibanserin 100mg daily among men receiving ADT for prostate cancer. We will recruit 50 men with prostate cancer who are receiving ADT and also endorse reduced sexual interest to participate. Men will be randomized to receive either daily flibanserin 100mg or placebo for a 12-week period. Patient-reported frequency of attempted sexual intercourse, sexual QoL, global QoL, and toxicity will be assessed at baseline and at pre-specified time points. Specific Aim 1 will assess the efficacy of flibanserin. The frequency of attempted sexual intercourse among men receiving flibanserin will be compared to men receiving placebo. The change in patient reported sexual QoL will also be compared between the study groups. Specific Aim 2 will assess the safety and tolerance of flibanserin. The frequency of grade 3+ adverse events and study drug discontinuation among men receiving flibanserin will be reported. The frequency of grade 2+ and grade 3+ patient reported adverse events will be compared between the flibanserin and placebo groups. Accomplishing these specific aims will provide us with a preliminary understanding about use of flibanserin in men receiving ADT for prostate cancer. This study will be conducted by a qualified multidisciplinary team of investigators with experience in both clinical trials and cancer survivorship research at the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center. The results of this clinical trial will be used to inform the design of a phase III clinical trial. Our long-term goal is to develop an evidence based treatment strategy that will significantly improve sexual health and QoL for prostate cancer survivors.

项目摘要 雄激素剥夺疗法（ADT）用于提高转移性和高风险男性的生存率 局限性前列腺癌不幸的是，ADT也与许多不良反应有关， 几乎所有接受这种治疗的男性都会出现功能障碍。性功能障碍是最常见的 前列腺癌患者的主诉，并导致生活质量（QoL）下降。性的丧失 特别是，对于患有前列腺癌的男性及其伴侣来说，这种兴趣是非常令人沮丧的， 这些患者的额外心理发病率。尽管性健康在前列腺患者中的重要性 癌症，以前的干预措施，以提高男性接受ADT的性兴趣几乎没有成功，和新的 需要战略。我们假设氟班色林可以用来增加男性的性欲 接受ADT治疗前列腺癌氟班色林是一种多功能5-羟色胺受体激动剂/拮抗剂， 作为突触后5-HT（1A）受体的激动剂和5-HT（2A）受体的拮抗剂， 被批准用于治疗女性性欲减退症。在本提案中，我们将进行双重 盲法、安慰剂对照、随机化II期临床试验，评估氟班色林100 mg的疗效和安全性 每天在接受ADT治疗前列腺癌的男性中。我们将招募50名前列腺癌患者， 接受ADT，也支持降低参与的性兴趣。男性将随机接受 每日氟班色林100 mg或安慰剂，持续12周。患者报告的尝试性行为的频率 将在基线和预定时间点评估性交、性生活质量、总体生活质量和毒性。 具体目标1将评估氟班色林的功效。性行为尝试的频率 将接受氟班色林的男性与接受安慰剂的男性进行比较。患者报告的性生活质量的变化 也将在研究组之间进行比较。具体目标2将评估安全性和耐受性 氟班色林接受以下治疗的男性中3+级不良事件和研究药物停药的频率 将报告氟班色林。2+级和3+级患者报告的不良事件的频率将为 氟班色林组和安慰剂组之间的比较。实现这些具体目标将为我们提供一个 对接受ADT治疗前列腺癌的男性使用氟班色林的初步了解。本研究将 由具有临床试验和癌症经验的合格多学科研究者团队进行 伯明翰奥尼尔综合癌症中心的亚拉巴马大学的生存研究。的 该临床试验的结果将用于为III期临床试验的设计提供信息。我们的长期目标是 制定循证治疗策略，显著改善前列腺的性健康和生活质量 癌症幸存者