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

NCT06917313 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000037181
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Keywords

adjuvant endocrine therapy; vasomotor symptoms; tamoxifen; aromatase

Outcome Measures

Primary Outcomes (1)

• Frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo

  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).

  Baseline to 12 weeks

Secondary Outcomes (4)

• Efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS

  At week 4, after treatment initiation

• Regression of mean daily frequency of moderate/severe VMS average

  Study duration: 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

• Differences in sleep quality using PROMIS Sleep Disturbance-Short Form 8b (PROMIS SD SF 8b)

  Baseline, week 4 and week 12

Study Arms (2)

Fezolinetant

ACTIVE COMPARATOR

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.

Drug: Fezolinetant

Placebo

PLACEBO COMPARATOR

Patients will be given placebo tablets to compare to active comparator.

Drug: Placebo

Interventions

Fezolinetant DRUG

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

Fezolinetant

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 18-40 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Yale University: lead
• Astellas Pharma US, Inc.: collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43201, United States

NOT YET RECRUITING

MeSH Terms

Interventions

fezolinetant

Study Officials

• Maryam Lustberg, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Kane

CONTACT

773-369-6904; laura.kane@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 8, 2025
• Study Start: December 5, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)