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

项目总结 雄激素剥夺疗法(ADT)用于提高转移和高危男性的存活率 局限性前列腺癌。不幸的是，ADT也与一些不良反应和性行为有关 几乎所有接受这种治疗的男性都会发生功能障碍。性功能障碍是最常见的 在患有前列腺癌的男性中抱怨，并导致较差的生活质量(QOL)。性欲的丧失 对于患有前列腺癌的男性和他们的伴侣来说，兴趣尤其令人痛苦，这对 这些患者的额外心理发病率。尽管前列腺癌男性的性健康很重要 癌症，以前为提高接受ADT治疗的男性的性兴趣而进行的干预措施收效甚微，而新的 战略是必要的。我们假设氟班色林可以用来提高男性的性欲 接受前列腺癌的ADT治疗。氟班丝林是一种多功能的5-羟色胺受体激动剂/拮抗剂 作为突触后5-羟色胺(1A)受体的激动剂和5-羟色胺(2A)受体的拮抗剂，以前 已被批准用于治疗女性性欲减退障碍。在这项提案中，我们将进行双倍 随机、盲法、安慰剂对照、II期临床试验评价氟班色林100 mg的疗效和安全性 每天在接受前列腺癌ADT治疗的男性中。我们将招募50名患有前列腺癌的男性 接受ADT，也支持减少性兴趣参与。男性将随机接受其中一项 每日服用氟班色林100毫克或安慰剂，疗程12周。患者报告的未遂性行为频率 性行为、性生活质量、全球生活质量和毒性将在基线和预先指定的时间点进行评估。 具体目标1将评估氟班色林的疗效。未遂性交的频度 服用氟班色林的男性将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 还将在研究组之间进行比较。具体目标2将评估安全和耐受性 氟班色林。在接受药物治疗的男性中，3级不良事件和研究停药的频率 氟班色林将被报告。2级和3级患者报告不良事件的频率为 比较了氟班色林组和安慰剂组。实现这些具体目标将为我们提供一个 氟班色林在前列腺癌患者接受ADT治疗中应用的初步了解。这项研究将是 由一个在临床试验和癌症方面都有经验的合格的多学科研究团队进行 阿拉巴马大学伯明翰分校奥尼尔综合癌症中心的生存研究。这个 这项临床试验的结果将用于第三阶段临床试验的设计。我们的长期目标是 制定循证治疗策略，显著改善前列腺癌患者的性健康和生活质量 癌症幸存者。

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.