Fezolinetant for Reducing Vasomotor Symptoms in Women with Breast Cancer on Endocrine Therapy, FLASH-Breast Trial
This phase II trial tests how well fezolinetant works to reduce hot flashes and night sweats (vasomotor symptoms) in women with breast cancer on endocrine therapy. Endocrine therapy medications can commonly cause vasomotor symptoms such as hot flashes, decreased libido, mood disorders, insomnia, and depression, can negatively impact a patient’s quality of life. They are frequently a cause for early treatment discontinuation. Fezolinetant works by blocking the activities of the NK3 receptor which is involved in the brain’s regulation of body temperature.
Inclusion Criteria
- Women with diagnosed, histologically confirmed, clinical stage I-III, hormone receptor positive (HR+) invasive breast cancer as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines for whom adjuvant endocrine therapy would be indicated, regardless of HER2 status
- Age 18 years and older
- Currently receiving endocrine therapy (tamoxifen or aromatase inhibitors [e.g., letrozole, anastrozole, or exemestane]) 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. 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 (follicle stimulating hormone [FSH] > 40 IU/L), or bilateral oophorectomy for at least 6 weeks before the screening visit, or if premenopausal chemically suppressed by gonadotrophin releasing hormone (GnRH) agonist therapy with ultrasensitive estradiol level < 10 * Premenopausal participants receiving ovarian suppression must agree to use an effective non-hormonal method of contraception during study participation and for at least 30 days after the last dose of the study drug ** Acceptable methods of contraception include: *** Intrauterine device (IUD) *** Total hysterectomy or bilateral tubal ligation *** Sexual abstinence (the reliability of abstinence must be evaluated concerning the duration of the clinical study and the participant's lifestyle) *** A vasectomized partner (provided the partner is the sole sexual partner of the study participant and that the vasectomized partner has received medical confirmation of the surgical success)
- 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
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, except CDK4/6 inhibitors as permitted and HER2-directed monoclonal antibody therapy (e.g., trastuzumab or pertuzumab) as specified
- 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 participants
- Known cirrhosis or active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) > 2 x upper limit of normal (ULN), or elevated total bilirubin, OR elevated direct bilirubin, or elevated international normalized ratio (INR), or elevated alkaline phosphatase > 2 x ULN
- Creatinine > 1.5 times upper limit of normal; or estimated GFR ≤ 30 mL/min per 1.73 m^2 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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06917313.
Locations matching your search criteria
United States
Connecticut
Derby
Fairfield
Greenwich
Guilford
New Haven
North Haven
Stamford
Torrington
Trumbull
Waterbury
Waterford
Rhode Island
Westerly
PRIMARY OBJECTIVE:
I. To evaluate the reduction in frequency of moderate to severe vasomotor symptoms (VMS) at 12 weeks of treatment with fezolinetant versus (vs.) placebo in breast cancer survivors on endocrine therapy (tamoxifen or aromatase inhibitors).
SECONDARY OBJECTIVES:
I. Evaluate the efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate to severe VMS at week 4 after treatment initiation.
II. Evaluate treatment activity among breast cancer survivors with moderate to severe VMS treated with fezolinetant vs. placebo at various segments of the entire course of patient participation.
III. Evaluate the difference in global quality of life in breast cancer survivors treated with fezolinetant vs. placebo using Functional Assessment of Cancer Therapy-Breast Endocrine Subscale (FACT-B ES).
IV. 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) at weeks 4 and 12.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive fezolinetant orally (PO) once daily (QD) for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
ARM II: Patients receive placebo PO QD for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients may then choose to receive fezolinetant PO QD for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 28 days.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationYale University
Principal InvestigatorMaryam Beheshti Lustberg
- Primary ID2000037181
- Secondary IDsNCI-2025-09480
- ClinicalTrials.gov IDNCT06917313