NCT06440967

Brief Summary

One of the standard treatments for women with breast cancer is hormone therapy, but this treatment can cause hot flashes. Hormone replacement therapy, or HRT, is most often prescribed for hot flashes for women in menopause but cannot be given to women on hormone therapy for breast cancer. Fezolinetant, an alternative to HRT, treats hot flashes for women in menopause. As hot flashes happen in the same way for women on hormone therapy for breast cancer, fezolinetant could help these women. In this study, women on hormone therapy for breast cancer who have moderate to severe hot flashes will take part. They will either take fezolinetant or a placebo to treat their hot flashes. The placebo looks like fezolinetant but doesn't have any medicine in it. The main aim of this study is to confirm if women who take fezolinetant have fewer hot flashes that are less severe compared to women who take the placebo. Women 18 years or older seeking treatment for hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. They are having hormone therapy for breast cancer from stage 0 (cancer cells that have not spread to nearby tissue) up to stage 3+ (the cancer has spread from the breast to the lymph nodes near the breast or the chest wall). The women will be assigned 1 of 2 study treatments (fezolinetant or placebo) by chance alone. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study treatments (fezolinetant or placebo). Women who take part in the study will take 1 tablet every day for 52 weeks (1 year). Each woman will be given an electronic handheld device with an app to track their hot flashes on a daily basis. Some women may be able to use the app on their own smartphone. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic about every 4 weeks for a health check. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo). After this visit the women will be called twice to check their health. The women will be in the study for about 2 years.

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
540

participants targeted

Target at P75+ for phase_3

Timeline
13mo left

Started Jul 2024

Typical duration for phase_3

Geographic Reach
11 countries

117 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress61%
Jul 2024Jun 2027

First Submitted

Initial submission to the registry

May 29, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 4, 2024

Completed
2 months until next milestone

Study Start

First participant enrolled

July 31, 2024

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2026

Expected
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

February 19, 2026

Status Verified

February 1, 2026

Enrollment Period

2.1 years

First QC Date

May 29, 2024

Last Update Submit

February 18, 2026

Conditions

Keywords

ESN364;vasomotor symptoms;fezolinetant;VEOZAH™

Outcome Measures

Primary Outcomes (4)

  • Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS

    Frequency of moderate and severe vasomotor symptoms (VMS) events will be calculated as the sum of moderate and severe VMS events per day.

    Baseline to Week 4

  • Mean change from Baseline to Week 12 in the frequency of moderate to severe VMS

    Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.

    Baseline to Week 12

  • Mean change from Baseline to Week 4 in the severity of moderate to severe VMS

    The severity of VMS will be calculated using a weighted average of VMS events.

    Baseline to Week 4

  • Mean change from Baseline to Week 12 in the severity of moderate to severe VMS

    The severity of VMS will be calculated using a weighted average of VMS events.

    Baseline to Week 12

Secondary Outcomes (55)

  • Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score

    Baseline to Week 12

  • Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score

    Baseline to Week 12

  • Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS

    Baseline to Week 24

  • Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS

    Baseline to Week 24

  • Number of participants with Treatment Emergent Adverse Events (TEAEs)

    Up to Week 55

  • +50 more secondary outcomes

Study Arms (2)

Fezolinetant

EXPERIMENTAL

Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.

Drug: FezolinetantDrug: TamoxifenDrug: Aromatase inhibitor

Placebo

PLACEBO COMPARATOR

Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.

Drug: PlaceboDrug: TamoxifenDrug: Aromatase inhibitor

Interventions

oral

Placebo

oral

FezolinetantPlacebo

oral

FezolinetantPlacebo

oral

Also known as: ESN364;, VEOZAH™
Fezolinetant

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participant has a personal history of stage 0-3 hormone receptor positive (HR+), either human epidermal growth factor receptor (HER)-2+ or HER-2- breast cancer; appropriate documentation includes a written or electronic report.
  • Participant must be receiving stable maintenance adjuvant endocrine therapy (e.g., tamoxifen or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months prior to randomization and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. If the participant is taking GnRH agonists/antagonists, therapy must also be stable for a minimum of 4 months prior to randomization. Add-on therapies for breast cancer adjuvant treatment (e.g., cyclin dependent kinase-4 (CDK4) inhibitors) are allowed.
  • Participant has a minimum average of 7 moderate to severe hot flashes (HFs) (vasomotor symptoms (VMS)) per day as recorded in the electronic daily diary (data must be available for at least 7 of the last 10 days prior to randomization).
  • Has an European Cooperative Oncology Group (ECOG) score 0 or 1.
  • Has at least 12-month life expectation.
  • Participant is born female.
  • Female participant: Is not pregnant and at least 1 of the following conditions apply:
  • Not a woman of childbearing potential (WOCBP)
  • WOCBP who has a negative urine or serum pregnancy test at screening and day 1 and agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational study intervention administration.
  • Female participant: Must not be breastfeeding or lactating starting at screening and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
  • Female participant: Must not donate ova starting at first administration of study intervention and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
  • Participant agrees not to participate in another interventional study while participating in the present study until the end of the 1-year extension follow-up period.
  • Participant's condition is stable as determined on the basis of medical history and general physical examination, hematology and biochemistry parameters, pulse rate and/or blood pressure and electrocardiogram (ECG) (or showing no clinically relevant deviations obtained within the last 3 months or at screening).
  • Participant has no new clinically significant findings on breast examination or from imaging (mammogram, breast ultrasound or equivalent). Results indicate that the participant is a good candidate for the study. Appropriate documentation includes a written or electronic report. In case of double mastectomy, imaging is not needed.
  • Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody screens).

You may not qualify if:

  • Participant has diagnosis of metastatic breast cancer (stage 4).
  • Participant has current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy except for HR+ breast cancer (stage 0 to 3) or basal cell carcinoma.
  • Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent.
  • Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated total bilirubin (TBL) or direct bilirubin (DBL), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to \< 2 × upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant with mildly elevated ALP (up to \< 1.5 × ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
  • Participant has creatinine \> 1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula \< 30 mL/min/1.73 m2 at the screening visit.
  • Participant has a history of endometrial hyperplasia (participant can be enrolled if she has undergone a hysterectomy) or uterine/endometrial cancer.
  • Participant has a medical condition or chronic disease (including history of neurological \[including cognitive\], hepatic, renal, cardiovascular, gastrointestinal, pulmonary \[e.g., moderate asthma\], endocrine, or gynecological disease) or malignancy that could confound interpretation of the study outcome.
  • Participant uses a prohibited therapy (menopause hormone therapy (MHT), estradiol-containing hormonal contraceptive progestin and progesterone-only medicines, any treatment for VMS \[prescription medications, over-the-counter, or herbal\] or CYP1A2 (cytochrome P450) inhibitors) or is not willing to wash out such drugs; in addition, medications that are contraindicated due to underlying breast cancer diagnosis and the adjuvant endocrine therapy.
  • Participant has a known substance abuse or alcohol addiction within 6 months of screening.
  • Participant has received any investigational therapy within 90 days or 5 half-lives, whichever is longer, prior to screening.
  • Participant has any condition, which makes the participant unsuitable for study participation.
  • Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvant endocrine therapy being used, or any components of the formulations used.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (117)

Site CA15019

Sarnia, Ontario, Canada

RECRUITING

Site CA15016

Sault Ste. Marie, Ontario, Canada

RECRUITING

Site CA15002

Montreal, Quebec, Canada

RECRUITING

Site CA15001

Québec, Quebec, Canada

RECRUITING

Site CA15004

Québec, Quebec, Canada

RECRUITING

Site CA15003

Sherbrooke, Quebec, Canada

RECRUITING

Site CA15020

Victoriaville, Quebec, Canada

RECRUITING

Site CA15018

Barrie, Canada

RECRUITING

Site CA15007

Trois-Rivières, Canada

RECRUITING

Site CZ42006

České Budějovice, Czechia

RECRUITING

Site CZ42003

Hořovice, Czechia

RECRUITING

Site CZ42002

Hradec Králové, Czechia

RECRUITING

Site CZ42011

Nový Jičín, Czechia

RECRUITING

Site CZ42001

Olomouc, Czechia

RECRUITING

Site CZ42005

Prague, Czechia

RECRUITING

Site CZ42008

Prague, Czechia

RECRUITING

Site CZ42013

Prague, Czechia

RECRUITING

Site CZ42004

Tábor, Czechia

RECRUITING

Site CZ42007

Vodňany, Czechia

RECRUITING

Site CZ42009

Vsetín, Czechia

RECRUITING

Site DK45007

Aalborg, Denmark

RECRUITING

Site DE45003

Esbjerg, Denmark

RECRUITING

Site DK45009

Hillerød, Denmark

RECRUITING

Site DK45002

Næstved, Denmark

RECRUITING

Site DE45008

Sønderborg, Denmark

RECRUITING

Site FR33003

Angers, France

RECRUITING

Site FR33001

Bayonne, France

RECRUITING

Site FR33005

Bordeaux, France

RECRUITING

Site FR33018

Bordeaux, France

RECRUITING

Site FR33017

Caen, France

RECRUITING

Site FR33016

Dijon, France

RECRUITING

Site FR33013

Le Mans, France

RECRUITING

Site FR33007

Lille, France

RECRUITING

Site FR33012

Lyon, France

RECRUITING

Site FR33008

Montpellier, France

RECRUITING

Site FR33002

Saint-Herblain, France

RECRUITING

Site GR49005

Essen, North Rhine-Westphalia, Germany

RECRUITING

Site DE49001

Bottrop, Germany

RECRUITING

Site GR49013

Dresden, Germany

RECRUITING

Site DE49009

Leipzig, Germany

RECRUITING

Site DE49007

Mönchengladbach, Germany

RECRUITING

Site DE49010

München, Germany

RECRUITING

Site GR49003

Münster, Germany

RECRUITING

Site GR49011

Witten, Germany

RECRUITING

Site GR49014

Wolfsburg, Germany

RECRUITING

Site HU36007

Budapest, Hungary

RECRUITING

Site HU36008

Budapest, Hungary

RECRUITING

Site HU36006

Debrecen, Hungary

RECRUITING

Site HU36001

Eger, Hungary

WITHDRAWN

Site HU36002

Kecskemét, Hungary

RECRUITING

Site HU36010

Salgótarján, Hungary

RECRUITING

Site HU36003

Székesfehérvár, Hungary

RECRUITING

Site IT39011

Bologna, Italy

RECRUITING

Site IT39015

Genova, Italy

RECRUITING

Site IT39003

Milan, Italy

RECRUITING

Site IT39013

Mirano, Italy

RECRUITING

Site IT39017

Pavia, Italy

RECRUITING

Site IT39018

Reggio Emilia, Italy

RECRUITING

Site IT39012

Terni, Italy

RECRUITING

Site IT39014

Tricase, Italy

RECRUITING

Site NL31014

Amsterdam, Netherlands

RECRUITING

Site NL31010

Breda, Netherlands

RECRUITING

Site NL31006

Dirksland, Netherlands

RECRUITING

Site NL31001

Haarlem, Netherlands

RECRUITING

Site NL31002

Rotterdam, Netherlands

RECRUITING

Site NL31004

Rotterdam, Netherlands

RECRUITING

Site NL31012

Rotterdam, Netherlands

RECRUITING

Site NL31009

Terneuzen, Netherlands

RECRUITING

Site PO48019

Poznan, Skorzewo, Poland

RECRUITING

Site PO48005

Bialystok, Poland

RECRUITING

Site PO48006

Bydgoszcz, Poland

RECRUITING

Site PO48004

Katowice, Poland

RECRUITING

Site PO48017

Katowice, Poland

RECRUITING

Site PO48015

Krakow, Poland

RECRUITING

Site PO48021

Krakow, Poland

RECRUITING

Site PO48007

Lodz, Poland

RECRUITING

Site PO48012

Lodz, Poland

RECRUITING

Site PO48020

Piła, Poland

RECRUITING

Site PO48002

Poznan, Poland

RECRUITING

Site PO48018

Poznan, Poland

RECRUITING

Site PO48010

Szczecin, Poland

RECRUITING

Site PO48003

Świdnik, Poland

RECRUITING

Site PO48001

Warsaw, Poland

RECRUITING

Site ES34011

Barcelona, Spain

RECRUITING

Site ES34020

Barcelona, Spain

RECRUITING

Site ES34021

Barcelona, Spain

RECRUITING

Site ES34010

Elche, Spain

RECRUITING

Site ES34003

Girona, Spain

RECRUITING

Site ES34005

Granada, Spain

RECRUITING

Site ES34006

Jaén, Spain

RECRUITING

Site ES34017

León, Spain

RECRUITING

Site ES34007

Madrid, Spain

RECRUITING

Site ES34019

Madrid, Spain

RECRUITING

Site ES34022

Madrid, Spain

RECRUITING

Site ES34023

Madrid, Spain

RECRUITING

Site ES34015

Majadahonda, Spain

RECRUITING

Site ES34002

Murcia, Spain

RECRUITING

Site ES34014

Murcia, Spain

RECRUITING

Site ES34008

Palma, Spain

RECRUITING

Site ES34025

Rivas-Vaciamadrid, Spain

RECRUITING

Site ES34009

Seville, Spain

RECRUITING

Site ES34024

Seville, Spain

RECRUITING

Site ES34013

Valencia, Spain

RECRUITING

Site GB44008

Bebington, Birkenhead, United Kingdom

RECRUITING

Site GB44009

Guildford, Surrey, United Kingdom

RECRUITING

Site GB44018

Aberdeen, United Kingdom

RECRUITING

Site GB44019

Birmingham, United Kingdom

RECRUITING

Site GB44003

Bristol, United Kingdom

RECRUITING

Site GB44016

Cambridge, United Kingdom

RECRUITING

Site GB44006

Glasgow, United Kingdom

RECRUITING

Site GB44002

Liverpool, United Kingdom

RECRUITING

Site GB44020

Liverpool, United Kingdom

RECRUITING

Site GB44005

London, United Kingdom

RECRUITING

Site GB44017

Oxford, United Kingdom

RECRUITING

Site GB44001

Preston Lancashire, United Kingdom

RECRUITING

Site GB44012

Redhill, United Kingdom

RECRUITING

Site GB44010

Stroke on Trent, United Kingdom

RECRUITING

Related Publications (1)

  • Liao C, Pal L. Novel Pharmacotherapies for Menopausal Symptoms. Obstet Gynecol. 2025 Oct 1;146(4):473-486. doi: 10.1097/AOG.0000000000006025. Epub 2025 Aug 7.

MeSH Terms

Conditions

Hot Flashes

Interventions

fezolinetantTamoxifenAromatase Inhibitors

Condition Hierarchy (Ancestors)

Signs and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

StilbenesBenzylidene CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsSteroid Synthesis InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesEstrogen AntagonistsHormone AntagonistsHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of Drugs

Study Officials

  • Medical Director

    Astellas Pharma Global Development, Inc.

    STUDY DIRECTOR

Central Study Contacts

Astellas Pharma Global Development, Inc.

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 29, 2024

First Posted

June 4, 2024

Study Start

July 31, 2024

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

June 30, 2027

Last Updated

February 19, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
More information

Locations