FLASH-Breast: Evaluating the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy

Официальное название

A Randomized Phase II Study to Evaluate the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy

Обзор

This is a phase II, randomized, double-blinded, placebo-controlled trial designed to evaluate the efficacy of fezolinetant (45 mg a day) vs. placebo in reducing moderate to severe vasomotor symptoms (VMS) in breast cancer survivors on endocrine therapy (tamoxifen, aromatase inhibitors). The trial will proceed in a single stage, and the total of 92 participants will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively.

Подробное описание

This is a phase II, randomized, double-blinded, placebo-controlled trial designed to evaluate the efficacy of fezolinetant (45 mg a day) vs. placebo in reducing moderate to severe vasomotor symptoms (VMS) in breast cancer survivors on endocrine therapy (tamoxifen, aromatase inhibitors). The trial will proceed in a single stage, and the total of 92 participants will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively. After the 7-14-day screening period when all the baseline, pre-treatment measures will be collected, we will record daily data on frequency and severity of VMS and calculate weekly averages of both metrics. After the 12 weeks treatment period, formal efficacy analysis will be conducted and the treatment with fezolinetant will be deemed efficacious if the final weekly average of daily frequency of VMS will be significantly reduced compared to the 'week12 - baseline' difference of the placebo arm. Upon conclusion of the formal 12-week treatment assignment, once VMS final assessment has been recorded, we will unblind the study participants to their treatment assignment. Participants will be then allowed to cross over shall they choose to do so. Due to the vast availability of safety and efficacy data in general population, we did not include interim efficacy/futility or safety analysis.

Our hypothesis is that neurokinin blockade by fezolinetant will significantly reduce vasomotor symptoms in breast cancer survivors on endocrine therapy (tamoxifen or aromatase-inhibitor) measured by mean change in frequency of moderate to severe VMS based on patient-reported data from baseline to 12-weeks.

Вмешательства

• Препарат Fezolinetant
  45 mg tablets, administered orally once daily with or without food, to be taken throughout the entire study phase, i.e. 12 weeks
• Препарат Placebo
  45 mg tablets, administered orally once daily with or without food, to be taken throughout the entire study phase, i.e. 12 weeks

Первичные конечные точки

• Frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo [Срок оценки: Baseline to 12 weeks]

Вторичные конечные точки (4)

• Efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS [Срок оценки: At week 4, after treatment initiation]
• Regression of mean daily frequency of moderate/severe VMS average [Срок оценки: Study duration: weeks 0-12]
• Change in global quality of life using Functional Assessment of Cancer Therapy - Breast, Endocrine Therapy Symptoms (FACT-B ES) [Срок оценки: Baseline to week 12]
• Differences in sleep quality using PROMIS Sleep Disturbance-Short Form 8b (PROMIS SD SF 8b) [Срок оценки: Baseline, week 4 and week 12]

Критерии участия

Критерии включения

Women with diagnosed, histologically confirmed, clinical stage I-III, HR+ invasive breast cancer as defined by ASCO CAP guidelines for whom adjuvant endocrine therapy would be indicated, regardless of HER2 status.

Age 18 years and older.

Currently on endocrine therapy (tamoxifen or aromatase inhibitors) as part of standard of care treatment for HR+ breast cancer. Endocrine therapy may be administered with or without ovarian suppression and/or CDK4/6 inhibitors as permitted in Section 7.1.1. Participants with HER2-positive disease are eligible and may receive concurrent HER2 monoclonal antibody therapy (e.g., trastuzumab or pertuzumab), but not HER2 antibody-drug conjugates (e.g., ado-trastuzumab emtansine T-DM1, or trastuzumab deruxtecan T-DXd).

Willing and able to provide written informed consent/assent for the trial.

Postmenopausal as defined by spontaneous amenorrhea for at least 12 consecutive months, spontaneous amenorrhea for at least 6 months with biochemical criteria or menopause (FSH > 40 IU/L), or bilateral oophorectomy for at least 6 weeks before the screening visit, or if premenopausal chemically suppressed by GnRH agonist therapy with ultrasensitive estradiol level <10.

On endocrine therapy for a minimum of 3 months and has planned duration of 12 weeks left in the treatment regimen. Participants receiving a CDK4/6 inhibitor must have been on treatment for at least 4 weeks prior to enrollment.

Experiencing an average of seven or more moderate to severe hot flashes per day over a 7-day period as documented by Symptom Diary during the Screening Period and seeking treatment or relief for VMS.

Able to swallow oral formulation of the study agent.

Критерии исключения

Participants who have a diagnosis of stage IV metastatic disease.

Receiving any other cancer treatment other than endocrine therapy. This includes chemotherapy, targeted therapies, and immunotherapy.

Receiving cytochrome CYP1A2 inhibitors.

Participants who have initiated, discontinued, or had a dose adjustment of treatment for vasomotor symptoms (prescription, over the counter, or herbal) within 28 days prior to screening.

Pregnant or lactating patients.

Known cirrhosis or active liver disease, jaundice, or elevated liver aminotransferases (ALT or AST) >2x ULN, or elevated total bilirubin, OR elevated direct bilirubin, or elevated INR, or elevated alkaline phosphatase >2x ULN.

Creatinine > 1.5 times upper limit of normal; or estimated GFR ≤ 30 mL/min per 1.73 m2 at screening.

Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Yale University — New Haven
• The Ohio State University Comprehensive Cancer Center — Columbus

Идентификаторы

NCT: NCT06917313 · 2000037181

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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