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

Phase 2

Not yet recruiting

• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
• Interventions: Drug: Fezolinetant; Drug: Placebo

• Registration Number: NCT06917313
• Lead Sponsor: Yale University

Brief Summary

This is a phase II, randomized, 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 patients will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively.

Detailed Description

This is a phase II, randomized, 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 patients 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, investigators 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, investigators 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, investigators did not include interim efficacy/futility or safety analysis.

Investigators 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.

Study Timeline

• Status Verified: 2025-01
• Study Start: 2025-04
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-01
• Last Update Submitted: 2025-04-01
• Study First Posted: 2025-04-08
• Last Update Posted: 2025-04-08
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 92

Inclusion Criteria

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.

BMI of 18-38 kg/m2

Age 40-65

Currently on endocrine therapy (tamoxifen or aromatase inhibitors)

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.

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.

Exclusion Criteria

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 received any treatment for vasomotor symptoms (prescription, over the counter, or herbal) for the last 28 days.

Pregnant or lactating patients

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fezolinetant	Fezolinetant	Fezolinetant is an oral medication, and the first neurokinin 3 (NK3) receptor antagonist approved by the FDA in May 2023 for treatment of moderate to severe hot flashes due to menopause. It blocks the activities of the NK3 receptor which is involved in the brain's regulation of body temperature.
Placebo	Placebo	Patients will be given placebo tablets to compare to active comparator.

Primary Outcome Measures

Name	Time	Method
Frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo	Baseline to 12 weeks	To evaluate the mean change reduction in frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo in breast cancer survivors on endocrine therapy (tamoxifen or aromatase inhibitors).

Secondary Outcome Measures

Name	Time	Method
Efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS	At week 4, after treatment initiation	To evaluate the efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS
Regression of mean daily frequency of moderate/severe VMS average	Study duration: weeks 0-12	To evaluate treatment activity among breast cancer survivors treated with fezolinetant vs placebo over the entire course of the study duration - measure by regression of mean daily frequency of moderate/severe VMS average every week of treatment (weeks 0-12)
Change in global quality of life using Functional Assessment of Cancer Therapy - Breast, Endocrine Therapy Symptoms (FACT-B ES)	Baseline to week 12	To evaluate the difference in global quality of life in breast cancer survivors treated with fezolinetant vs placebo using FACT-B ES. The total score range is 0 to 164, with higher scores indicating better quality of life
Differences in sleep quality using PROMIS Sleep Disturbance-Short Form 8b (PROMIS SD SF 8b)	Baseline, week 4 and week 12	To evaluate the differences in sleep quality in breast cancer survivors' treatment with fezolinetant vs placebo using patient-reported outcomes measurement information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b. Total score is calculated by summing the items (range: 8-40), with a higher score meaning more disturbed sleep.

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States