A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 16
- 主要终点
- Change in the maximally changed cognitive domain
研究概览
简要总结
This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with metastatic and non-metastatic castration resistant prostate cancer (CRPC) or metastatic hormone sensitive prostate cancer (HSPC). Approximately 132 patients will be enrolled. Eligible patients will be randomized in a 1:1 fashion to treatment with enzalutamide 160 mg orally daily or darolutamide 600 mg orally twice daily, in combination with standard LHRH agonist based treatment. Cognitive assessments will be performed using modules from Cambridge Neuropsychological Test Automated Battery (CANTAB) an internationally recognized software for assessing cognitive function and impairment.
详细描述
The goal of the trial is to assess cognitive and quality of life outcomes over the 48-week primary data collection period of the trial. This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with Advanced prostate cancer: metastatic and non-metastatic castration resistant prostate cancer (CRPC) or metastatic hormone sensitive prostate cancer (HSPC).
The primary endpoint will be the percent change in the maximally changed cognitive domain by 24 weeks in each study arm. Patients will be stratified by age (<65, 65-80, > 80). Patients will be allowed to cross over from either treatment to the opposite treatment arm at 12 and 24 weeks if they meet any of the cross-over criteria as described in the protocol.
Cognitive assessments will be performed using Cambridge Neuropsychological Test Automated Battery (CANTAB), an internationally recognized software for assessing cognitive function and impairment. Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
Blood samples will be collected for exploratory genomic analyses (AR CAG repeat length, PHS, exosome analysis).
Patients will have the option to opt into an additional separate MRI sub-study. A subset of 40 patients (20 per arm) will undergo fMRI to measure percent signal change in the HP PFC circuit at baseline, 24 and 48 weeks or/and cross-over/end of treatment visit (if applicable).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate
- •Progressive disease per PCWG3 criteria with EITHER: Metastatic CRPC or non- metastatic CRPC (M0CRPC)
- •For mCRPC: metastatic disease documented by standard or novel imaging techniques
- •OR for M0CPRC: no evidence of metastatic disease on standard imaging.
- •Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the patient is medically castrated, continuous dosing with GnRH agonist or antagonist must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Able to complete cognitive testing and patient reported outcome surveys in English.
- •Ability to swallow study medications whole.
- •Able to provide informed consent.
排除标准
- 未提供
研究组 & 干预措施
Darolutamide (DARO)
Patients will take DARO at a dose of 600 mg (300 mg ×2 tablets) by mouth twice daily beginning on Day 1, of Week 1. Patients will take DARO throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy.
干预措施: Darolutamide (Drug)
Enzalutamide (ENZ)
Patients will take ENZ at a dose of 160 mg PO once daily (QD), beginning on Day 1, of Week 1. Patients will take ENZ throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Change in the maximally changed cognitive domain
时间窗: 24 weeks
To compare the effects of treatment with enzalutamide (ENZ) versus darolutamide (DARO) on the cognitive function of men with non-metastatic and metastatic castration-resistant prostate cancer by comparing the change in the maximally changed cognitive domain utilizing Cambridge Neuropsychological Test Automated Battery \[CANTAB\] cognitive tests from baseline in patients in each study arm.Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
次要结局
- Proportion of impaired patients(48 weeks)
- Improve in cognitive function after crossover(48 weeks)
- Crossover from enzalutamide to darolutamide and darolutamide to enzalutamide(48 weeks)
- Change in lowest ranking domain(48 weeks)
- Prostate-specific antigen (PSA) response rate(24 weeks)
- Maximally changed cognitive domain(48 weeks)
- Prostate-specific antigen (PSA) progression.(104 weeks)
- Progression free survival(104 weeks)