Hot FlashesPhase 3NCT06440967
A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy
A Phase 3 study testing Fezolinetant, Tamoxifen and Aromatase inhibitor in people with Hot Flashes, run by Astellas Pharma Global Development, Inc. at 110 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Hot Flashes
- What is being tested?
- Fezolinetant, Tamoxifen and Aromatase inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 982 participants
- Where
- 110 sitesin 11 countries
- Study dates
- 31 Jul 2024to 30 Apr 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
110 sites in 11 countries.
110 sites in 11 countries
Spain19 sites
Site ES34011
Barcelona
Site ES34020
Barcelona
Site ES34010
Elche
Site ES34003
Girona
Site ES34005
Granada
Site ES34006
Jaén
Site ES34017
León
Site ES34007
Madrid
Site ES34019
Madrid
Site ES34022
Madrid
Site ES34023
Madrid
Site ES34015
Majadahonda
Site ES34002
Murcia
Site ES34014
Murcia
Site ES34008
Palma
Site ES34025
Rivas-Vaciamadrid
Site ES34009
Seville
Site ES34024
Seville
Site ES34013
Valencia
Poland14 sites
Site PO48005
Bialystok
Site PO48006
Bydgoszcz
Site PO48004
Katowice
Site PO48017
Katowice
Site PO48015
Krakow
Site PO48021
Krakow
Site PO48007
Lodz
Site PO48012
Lodz
Site PO48019
Poznan, Skorzewo
Site PO48002
Poznan
Site PO48018
Poznan
Site PO48003
Świdnik
Site PO48010
Szczecin
Site PO48001
Warsaw
United Kingdom14 sites
Site GB44018
Aberdeen
Site GB44008
Bebington, Birkenhead
Site GB44019
Birmingham
Site GB44003
Bristol
Site GB44016
Cambridge
Site GB44006
Glasgow
Site GB44009
Guildford, Surrey
Site GB44002
Liverpool
Site GB44020
Liverpool
Site GB44005
London
Site GB44017
Oxford
Site GB44001
Preston Lancashire
Site GB44012
Redhill
Site GB44010
Stroke on Trent
Czechia11 sites
Site CZ42006
České Budějovice
Site CZ42003
Hořovice
Site CZ42002
Hradec Králové
Site CZ42011
Nový Jičín
Site CZ42001
Olomouc
Site CZ42005
Prague
Site CZ42008
Prague
Site CZ42013
Prague
Site CZ42004
Tábor
Site CZ42007
Vodňany
Site CZ42009
Vsetín
France11 sites
Site FR33003
Angers
Site FR33001
Bayonne
Site FR33005
Bordeaux
Site FR33018
Bordeaux
Site FR33017
Caen
Site FR33016
Dijon
Site FR33013
Le Mans
Site FR33007
Lille
Site FR33012
Lyon
Site FR33008
Montpellier
Site FR33002
Saint-Herblain
Canada8 sites
Site CA15002
Montreal, Quebec
Site CA15001
Québec, Quebec
Site CA15004
Québec, Quebec
Site CA15019
Sarnia, Ontario
Site CA15016
Sault Ste. Marie, Ontario
Site CA15003
Sherbrooke, Quebec
Site CA15007
Trois-Rivières
Site CA15020
Victoriaville, Quebec
Germany8 sites
Site DE49001
Bottrop
Site GR49013
Dresden
Site GR49005
Essen, North Rhine-Westphalia
Site DE49009
Leipzig
Site DE49007
Mönchengladbach
Site DE49010
München
Site GR49003
Münster
Site GR49014
Wolfsburg
Italy7 sites
Site IT39011
Bologna
Site IT39015
Genova
Site IT39003
Milan
Site IT39013
Mirano
Site IT39017
Pavia
Site IT39018
Reggio Emilia
Site IT39012
Terni
Netherlands7 sites
Site NL31010
Breda
Site NL31006
Dirksland
Site NL31001
Haarlem
Site NL31002
Rotterdam
Site NL31004
Rotterdam
Site NL31012
Rotterdam
Site NL31009
Terneuzen
Hungary6 sites
Site HU36008
Budapest
Site HU36006
Debrecen
Site HU36001
Eger
Site HU36002
Kecskemét
Site HU36010
Salgótarján
Site HU36003
Székesfehérvár
Denmark5 sites
Site DK45007
Aalborg
Site DE45003
Esbjerg
Site DK45009
Hillerød
Site DK45002
Næstved
Site DE45008
Sønderborg
About this study
Official title: A Randomized, Placebo-controlled, Double-blind, Phase 3 Clinical Study to Investigate the Efficacy and Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms (Hot Flashes) in Women With Stage 0 to 3 Hormone Receptor-positive Breast Cancer Who Are Receiving Adjuvant Endocrine Therapy
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.
Read more
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.
- Conditions
- Hot Flashes
- Being tested
- Fezolinetant, Placebo, Tamoxifen, Aromatase inhibitor
- Keywords
- ESN364;, vasomotor symptoms;, fezolinetant;, VEOZAH™
- Medical subject headings
- Hot Flashes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FezolinetantDrug
Also called ESN364;, VEOZAH™
oral
PlaceboDrug
oral
TamoxifenDrug
oral
Aromatase inhibitorDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fezolinetant; Drug: Tamoxifen; Drug: 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. Receives: Drug: Placebo; Drug: Tamoxifen; Drug: Aromatase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 12
Secondary outcomes (55)
Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score
The Menopause-specific Quality of Life Questionnaire (MENQOL) is a 29-item patient-reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. The overall questionnaire score is the mean of the domain means. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference in MENQoL.
Measured: Baseline to Week 12
Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score
The Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) assesses self-reported sleep disturbance over the past 7 days and includes perceptions of: restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Responses to each of the 8 items range from 1 to 5 and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the concept measured (disturbed sleep).
Measured: Baseline to Week 12
Mean change from Baseline to Week 24 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.
Measured: Baseline to Week 24
Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS
The severity of VMS will be calculated using a weighted average of VMS events.
Measured: Baseline to Week 24
Number of participants with Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as Adverse Event (AE) observed after starting administration of the investigational study intervention and up to 21 days after the last dose of investigational study intervention.
Measured: Up to Week 55
Number of participants with Adverse Events of Special Interest (AESIs)
AEs of special interest in this study will include: Progression of breast cancer including metastasis; Adverse events of uterine bleeding; Adverse events of liver test elevations; Any liver AE leading to discontinuation.
Measured: Up to Week 55
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Measured: Up to Week 55
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values.
Measured: Up to Week 55
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant ECG values.
Measured: Up to Week 52
Mean change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 1 to 3
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Measured: Baseline and Weeks 1 to 3
Mean Change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 5 to 11
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Measured: Baseline and Weeks 5 to 11
Mean change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 1 to 3
The severity of VMS will be calculated using a weighted average of VMS events.
Measured: Baseline and Weeks 1 to 3
Mean Change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 5 to 11
The severity of VMS will be calculated using a weighted average of VMS events.
Measured: Baseline and Weeks 5 to 11
Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of >/= 50% will be reported.
Measured: Baseline to Weeks 1, 4, 8 and 12
Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of >/= 75% will be reported.
Measured: Baseline to Weeks 1, 4, 8 and 12
Percent reduction at 100% in the frequency of moderate and severe VMS from baseline
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of 100% will be reported.
Measured: Baseline to Weeks 1, 4, 8 and 12
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen
CL/F will be derived using a population PK model.
Measured: Up to Week 24
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen in Plasma: CL/F
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen in Plasma: Vc/F
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen in Plasma: Cavg
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen in Plasma: Ctrough
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: CL/F
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Cavg
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
PK of aromatase inhibitors in Plasma: CL/F
CL/F will be derived using a population PK model.
Measured: Up to Week 24
PK of aromatase inhibitors in Plasma: Vc/F
Vc/F will be derived using a population PK model.
Measured: Up to Week 24
PK of aromatase inhibitors in Plasma: Cavg
Cavg will be derived using a population PK model.
Measured: Up to Week 24
PK of aromatase inhibitors in Plasma: Ctrough
Ctrough will be derived using a population PK model.
Measured: Up to Week 24
Mean change from Baseline in the MENQOL Total Score
The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. The total score is the mean of the domain means. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL.
Measured: Baseline to Weeks 4, 8, 12 and 24
Mean change from Baseline in the MENQOL VMS 1-week recall domain score
The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Measured: Baseline to Weeks 4, 8 and 24
Mean change from Baseline in the MENQOL psychosocial 1-week recall domain score
The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Measured: Baseline to Weeks 4, 8, 12 and 24
Mean change from Baseline in the MENQOL physical 1-week recall domain score
The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Measured: Baseline to Weeks 4, 8, 12 and 24
Mean change from Baseline in the MENQOL sexual 1-week recall domain score
The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Measured: Baseline to Weeks 4, 8, 12 and 24
Mean change from Baseline in the PROMIS SD SF 8b Total (raw) Score
The PROMIS SD SF 8b assesses self reported sleep disturbance over the past 7 days and includes perceptions of: restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Responses to each of the 8 items range from 1 to 5 and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the concept measured (disturbed sleep).
Measured: Baseline to Weeks 4, 8 and 24
Scores on the Patient Global Impression of Change (PGI-C) VMS
The PGI-C VMS evaluates patient perceived change in hot flashes/night sweats from the initiation of treatment. Ratings range from (1) much better to (7) much worse.
Measured: Up to Week 24
Change from Baseline in the Patient Global Impression of Severity (PGI-S) VMS Score
The PGI-S VMS evaluates patient perceived severity of hot flashes/night sweats. Ratings range from (1) no problems to (4) severe problems.
Measured: Baseline to Weeks 4, 8, 12 and 24
Scores on the PGI-C sleep disturbance (SD)
PGI-C SD evaluates patient perceived change in sleep disturbance from the initiation of treatment. Ratings range from (1) much better to (7) much worse.
Measured: Up to Week 24
Change from Baseline in the PGI-S SD Score
The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems.
Measured: Baseline to Weeks 4, 8, 12 and 24
PGI-S SD response
Proportion of patients achieving a response in PGI-S SD. The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems. PGI-S SD response is defined as at least 2 levels of improvement on PGI-S SD from baseline. Non-response is defined as not achieving a response.
Measured: Up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start31 Jul 2024
- Primary completion25 Jun 2026
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hot FlashesStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 982 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06440967
- Sponsor's protocol ID
- 2693-CL-1303
- Other IDs
- 2024-510719-31-00
- Status last verified
- Sep 2026
- First submitted
- 29 May 2024
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
Publications
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.
PubMed 40773756
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind, Phase 3 Clinical Study to Investigate the Efficacy and Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms (Hot Flashes) in Women With Stage 0 to 3 Hormone Receptor-positive Breast Cancer Who Are Receiving Adjuvant Endocrine Therapy
- ClinicalTrials.gov ID
- NCT06440967
- Acronym / sponsor ID
- 2693-CL-1303
- Conditions
- Hot Flashes
- Keywords
- ESN364;, vasomotor symptoms;, fezolinetant;, VEOZAH™
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 982 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Jul 2024 (actual)
- Primary completion
- 25 Jun 2026 (actual)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 4 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fezolinetant | Experimental | Drug: Fezolinetant, Drug: Tamoxifen, Drug: Aromatase inhibitorParticipants 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. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Tamoxifen, Drug: Aromatase inhibitorParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FezolinetantAlso: ESN364;, VEOZAH™oral | Drug | Fezolinetant |
| Placebooral | Drug | Placebo |
| Tamoxifenoral | Drug | Fezolinetant, Placebo |
| Aromatase inhibitororal | Drug | Fezolinetant, Placebo |
Primary outcome
Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS
Time frame: Baseline to Week 4
Frequency of moderate and severe vasomotor symptoms (VMS) events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 12 in the frequency of moderate to severe VMS
Time frame: Baseline to Week 12
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 4 in the severity of moderate to severe VMS
Time frame: Baseline to Week 4
The severity of VMS will be calculated using a weighted average of VMS events.
Mean change from Baseline to Week 12 in the severity of moderate to severe VMS
Time frame: Baseline to Week 12
The severity of VMS will be calculated using a weighted average of VMS events.
55 secondary outcomes
Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score
Time frame: Baseline to Week 12
Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score
Time frame: Baseline to Week 12
Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS
Time frame: Baseline to Week 24
Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS
Time frame: Baseline to Week 24
Number of participants with Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Week 55
Number of participants with Adverse Events of Special Interest (AESIs)
Time frame: Up to Week 55
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Time frame: Up to Week 55
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Time frame: Up to Week 55
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Time frame: Up to Week 52
Mean change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 1 to 3
Time frame: Baseline and Weeks 1 to 3
Mean Change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 5 to 11
Time frame: Baseline and Weeks 5 to 11
Mean change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 1 to 3
Time frame: Baseline and Weeks 1 to 3
Mean Change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 5 to 11
Time frame: Baseline and Weeks 5 to 11
Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline
Time frame: Baseline to Weeks 1, 4, 8 and 12
Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline
Time frame: Baseline to Weeks 1, 4, 8 and 12
Percent reduction at 100% in the frequency of moderate and severe VMS from baseline
Time frame: Baseline to Weeks 1, 4, 8 and 12
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen
Time frame: Up to Week 24
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen
Time frame: Up to Week 24
PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors
Time frame: Up to Week 24
PK of tamoxifen in Plasma: CL/F
Time frame: Up to Week 24
PK of tamoxifen in Plasma: Vc/F
Time frame: Up to Week 24
PK of tamoxifen in Plasma: Cavg
Time frame: Up to Week 24
PK of tamoxifen in Plasma: Ctrough
Time frame: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg
Time frame: Up to Week 24
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough
Time frame: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg
Time frame: Up to Week 24
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough
Time frame: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: CL/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F
Time frame: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Cavg
Time frame: Up to Week 24
PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough
Time frame: Up to Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Derived from this study: PubMed 40773756Liao 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.
- Individual participant dataSharing planned: Yes. 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Astellas Pharma Global Development, Inc.
110 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fezolinetant, Tamoxifen and Aromatase inhibitor in people with Hot Flashes, run by Astellas Pharma Global Development, Inc. at 110 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 110 sites in Spain, Poland, United Kingdom, Czechia, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS (time frame: Baseline to Week 4). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06440967, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.