Phase 2 Randomized, Cross-over Trial of Fezolinetant for Treatment of Vasomotor Symptoms in Patients Taking Endocrine Therapy (VEnT)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Change in frequency of vasomotor symptoms (VMS)
研究概览
简要总结
This phase II trial tests how well fezolinetant works in improving vasomotor symptoms (VMS) in breast cancer patients taking endocrine therapy (ET). Anti-hormone treatments are effective for lowering the risk of breast cancer but can cause bothersome VMS, such as hot flashes and night sweats. Fezolinetant inhibits the activity of the neurokinin type 3 receptor and has shown activity against VMS in postmenopausal women. Taking fezolinetant may work well at improving VMS in breast cancer patients taking ET.
详细描述
15APR2026- Amendment processed to revise the statistical analysis plan, because the trial is being terminated early due to poor accrual. We are switching the analysis plan to be descriptive because of poor accrual. Additionally, we are removing the exploratory analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All study drug will be blinded to the patients, the study investigators, and the study coordinators to ensure masking of the treatments. The statistician and the study investigators will remain blinded until the study database is locked. The only study personnel that will not be blinded are the research pharmacy staff in order to facilitate randomization codes and treatment delivery, and in case emergency unblinding is required.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female subject aged ≥ 18 years
- •Taking endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) for adjuvant treatment of stage 1-3 breast cancer or for chemoprevention (breast ductal carcinoma in situ [DCIS] or high risk)
- •Planning to take the same endocrine therapy for at least 10 weeks after study drug initiation
- •Report 28 or more VMS episodes, at least some of which are severe or bothersome, during the 7-day screening period
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) within 28 days prior to randomization
- •Total bilirubin < 2 x ULN within 28 days prior to randomization
- •Completion of chemotherapy, if given. Concurrent use of gonadotropin releasing hormone agonist (GnRHa) therapy, anti-HER2 therapy, bisphosphonate therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, and abemaciclib therapy is permitted
- •Patients receiving treatment with selective serotonin reuptake inhibitor (SSRIs), serotonin and norepinephrine reuptake inhibitor (SNRIs), gabapentinoids, clonidine, or oxybutynin must have been taking a stable dose for at least 30 days prior to enrollment if they plan to continue the drug during study participation, and willing to remain on the treatment for the duration of study participation. If they do not plan to take the medication during study participation, they should stop the medication at least 7 days before the start of the VMS screening period
- •Patients taking over-the-counter supplements or herbal medications for treatment of VMS must stop the medication at least 7 days before the start of the VMS screening period
- •Able to self-complete questionnaires in English
- •Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
- •For women of childbearing potential, participants must agree to use an effective contraceptive method during protocol therapy and for 3 months following completion of protocol therapy with details provided as a part of the consent process and must have a negative pregnancy test at screening. In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, and bilateral tubal ligation/occlusion
排除标准
- •Metastatic breast cancer
- •Prior treatment with fezolinetant
- •Known severe renal disease (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m^2)
- •Known cirrhosis
- •Pregnant or breast feeding, or plan to become pregnant during the study period or within 3 months of completing study medication
- •Concomitant use of CYP1A2 inhibitors, including but not limited to fluvoxamine, ciprofloxacin, cimetidine, citalopram, and ribociclib
- •Concomitant use of systemic or transdermal estrogen products
- •Known allergy or hypersensitivity to fezolinetant or any of the excipients in the medication
- •Unable to take oral medications
- •Any medical condition that would interfere with the absorption of study medication. Prior gastric bypass is permitted
- •Concurrent medical disease that could confound or interfere with evaluation of VMS
- •Patients with a prior or concurrent malignancy whose natural history or treatment, in the opinion of the treating investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- •Patients who are participating concurrently in another interventional study (actually receiving a study medication) or participated in an interventional study within 30 days prior to screening or received any investigational drug within 30 days or within 5 half-lives prior to screening, whichever is longer
研究组 & 干预措施
Arm I (fezolinetant, placebo)
Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (fezolinetant, placebo)
Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Fezolinetant (Drug)
Arm I (fezolinetant, placebo)
Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Placebo Administration (Drug)
Arm I (fezolinetant, placebo)
Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm I (fezolinetant, placebo)
Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Questionnaire Administration (Other)
Arm II (placebo, fezolinetant)
Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (placebo, fezolinetant)
Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Placebo Administration (Drug)
Arm II (placebo, fezolinetant)
Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo, fezolinetant)
Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Questionnaire Administration (Other)
Arm II (placebo, fezolinetant)
Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.
干预措施: Fezolinetant (Drug)
结局指标
主要结局
Change in frequency of vasomotor symptoms (VMS)
时间窗: Baseline to day 71
Will perform an intent-to-treat analysis. The mean change in frequency of VMS with 4 weeks of fezolinetant versus placebo will be reported with the corresponding 95% confidence interval. Initial analysis will use a paired t-test of the mean change in frequency of VMS with 4 weeks of treatment with drug and placebo.
次要结局
- Incidence of adverse events(Baseline through 30 days after the last dose of study treatment)
- Change of the severity of VMS(Baseline to day 71)
- Change of the hot flash score(Baseline to day 71)
- Change of the Menopause-Specific Quality of Life (MENQOL) hot flash subscore(Baseline to day 71)
- Patient Global Impression of Change (PGIC) for hot flashes and night sweats(Baseline to day 71)
- Change of the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance(Baseline to day 71)