Fezolinetant for the Improvement of Vasomotor Symptoms in Breast Cancer Patients Taking Endocrine Therapy, VENT Trial

Phase 2

Recruiting

• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Breast Ductal Carcinoma In Situ; Localized Breast Carcinoma
• Interventions: Procedure: Biospecimen Collection; Drug: Fezolinetant; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT06617455
• Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-24
• Study First Submitted QC: 2024-09-24
• Study First Posted: 2024-09-27
• Study Start: 2024-10-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-08
• Primary Completion: 2026-07-01
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 36

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm II (placebo, fezolinetant)	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.
Arm I (fezolinetant, placebo)	Placebo Administration	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.
Arm I (fezolinetant, placebo)	Biospecimen Collection	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.
Arm I (fezolinetant, placebo)	Quality-of-Life Assessment	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.
Arm I (fezolinetant, placebo)	Questionnaire Administration	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.
Arm II (placebo, fezolinetant)	Biospecimen Collection	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.
Arm II (placebo, fezolinetant)	Placebo Administration	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.
Arm II (placebo, fezolinetant)	Quality-of-Life Assessment	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.
Arm II (placebo, fezolinetant)	Questionnaire Administration	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.
Arm I (fezolinetant, placebo)	Fezolinetant	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.

Primary Outcome Measures

Name	Time	Method
Change in frequency of vasomotor symptoms (VMS)	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. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.

Secondary Outcome Measures

Name	Time	Method
Change of the severity of VMS	Baseline to day 71	The mean change of the severity of VMS, as assessed with the hot flash log, with 4 weeks of fezolinetant versus placebo. Will perform an intent-to-treat analysis. Will be reported with corresponding 95% confidence intervals. Initial analysis will use a paired t-test of the mean change in severity of VMS from baseline to week 4 between drug and placebo. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.
Change of the hot flash score	Baseline to day 71	The mean change of the hot flash score, as assessed with the hot flash log and calculated by multiplying VMS frequency by severity, with 4 weeks of fezolinetant versus placebo. Will perform an intent-to-treat analysis. Will be reported with corresponding 95% confidence intervals. Initial analysis will use a paired t-test of the mean change in hot flash score from baseline to week 4 between drug and placebo. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.
Change of the Menopause-Specific Quality of Life (MENQOL) hot flash subscore	Baseline to day 71	The mean change of the MENQOL hot flash subscore with 4 weeks of fezolinetant versus placebo. Will perform an intent-to-treat analysis. Will be reported with corresponding 95% confidence intervals. Initial analysis will use a paired t-test of the mean change in MENQOL hot flash subscore from baseline to week 4 between drug and placebo. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.
Patient Global Impression of Change (PGIC) for hot flashes and night sweats	Baseline to day 71	The mean PGIC for hot flashes and for night sweats after 4 weeks of fezolinetant versus placebo. Will perform an intent-to-treat analysis. Will be reported with corresponding 95% confidence intervals. Initial analysis will use a paired t-test of PGIC score from baseline to week 4 between drug and placebo. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.
Change of the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance	Baseline to day 71	The mean change of the PROMIS Sleep Disturbance T score with 4 weeks of fezolinetant versus placebo. Will perform an intent-to-treat analysis. Will be reported with corresponding 95% confidence intervals. Initial analysis will use a paired t-test of the mean change in PROMIS Sleep Disturbance from baseline to week 4 between drug and placebo. Follow up analyses will use a linear mixed effects model (with any transformation needed for assumptions to be met) with random intercept that considers the repeated measurements, possible sequence, period, and carryover effects.
Incidence of adverse events	Baseline through 30 days after the last dose of study treatment	Safety will be assessed throughout the trial and adverse events during the 10 weeks of study participation will be reported using descriptive statistics for fezolinetant and for placebo. Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Trial Locations

Locations (1)

University of Michigan Rogel Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States