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: 10407479
• 负责人: Andrew M McDonald
• 金额: $ 17.01万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10407479
• 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; Placebo Control; 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; antagonist; arm; cabergoline; cardiovascular effects; design; experience; flibanserin; high risk; improved; inhibitor; 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.

项目概要 雄激素剥夺疗法（ADT）用于提高患有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，例如性行为 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 前列腺癌男性的抱怨并导致生活质量 (QoL) 恶化。性欲的丧失 对于患有前列腺癌的男性及其伴侣来说，兴趣尤其令人痛苦，这有助于 这些患者的额外心理发病率。尽管性健康对于患有前列腺疾病的男性很重要 癌症、之前针对接受 ADT 的男性提高性兴趣的干预措施收效甚微，而新的 需要采取策略。我们假设氟班色林可用于增加男性的性欲 接受 ADT 治疗前列腺癌。氟班色林是一种多功能血清素受体激动剂/拮抗剂，其作用 作为突触后 5-HT(1A) 受体的激动剂和 5-HT(2A) 受体的拮抗剂，此前已 已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 评估氟班色林 100mg 有效性和安全性的盲法、安慰剂对照、随机 II 期临床试验 每天接受 ADT 治疗前列腺癌的男性。我们将招募 50 名患有前列腺癌的男性，他们是 接受 ADT 并认可参与性兴趣降低。男性将被随机分配接受 每日氟班色林 100 毫克或安慰剂，持续 12 周。患者报告的尝试性行为的频率 将在基线和预先指定的时间点评估性交、性生活质量、整体生活质量和毒性。 具体目标 1 将评估氟班色林的功效。尝试性交的频率 将接受氟班色林治疗的男性与接受安慰剂治疗的男性进行比较。患者报告性生活质量的变化 研究组之间也将进行比较。具体目标 2 将评估以下药物的安全性和耐受性： 氟班色林。接受治疗的男性中 3 级以上不良事件和研究药物停药的频率 将报告氟班色林。患者报告的 2+ 级和 3+ 级不良事件的频率为 比较氟班色林组和安慰剂组。实现这些具体目标将为我们提供 对接受 ADT 治疗前列腺癌的男性使用氟班色林的初步了解。这项研究将 由具有临床试验和癌症经验的合格多学科研究人员团队进行 阿拉巴马大学伯明翰奥尼尔综合癌症中心的生存研究。这 该临床试验的结果将用于指导 III 期临床试验的设计。我们的长期目标是 制定基于证据的治疗策略，将显着改善前列腺的性健康和生活质量 癌症幸存者。