A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy

NCT06440967
clinicaltrials.gov
Phase
Phase 3
clinicaltrials.gov
Recruitment status
Active, not recruiting
clinicaltrials.gov
Participants
982
clinicaltrials.gov
Lead sponsor
Astellas Pharma Global Development, Inc.
clinicaltrials.gov
Start date
2024-07-31
clinicaltrials.gov
Number of sites
110
clinicaltrials.gov

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.
clinicaltrials.gov
Short title
A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy
clinicaltrials.gov
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

Control arm
Placebo
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Active, not recruiting
clinicaltrials.gov
Phase
Phase 3
clinicaltrials.gov
Study type
Interventional
clinicaltrials.gov

Completion date
2028-04-30
clinicaltrials.gov
First posted
2024-06-04
clinicaltrials.gov
Registry last updated
2026-10-27
clinicaltrials.gov
Primary completion date
2026-06-25
clinicaltrials.gov
Start date
2024-07-31
clinicaltrials.gov

Actual participants
982
clinicaltrials.gov
Participants
982
clinicaltrials.gov
Participant count basis
Actual
clinicaltrials.gov
Protocol amendments
7
clinicaltrials.gov
Number of sites
110
clinicaltrials.gov

Data monitoring committee
Yes
clinicaltrials.gov
Registry sponsor category
Industry
clinicaltrials.gov
Lead sponsor
Astellas Pharma Global Development, Inc.
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT06440967
clinicaltrials.gov
ClinicalTrials.gov ID
NCT06440967
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

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

    Timeframe: 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.

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

    Timeframe: 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.

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

    Timeframe: Baseline to Week 4

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

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

    Timeframe: Baseline to Week 12

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

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

    Timeframe: Baseline to Week 12

    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.

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

    Timeframe: Baseline to Week 12

    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).

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

    Timeframe: Baseline to Week 24

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

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

    Timeframe: Baseline to Week 24

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

  5. Number of participants with Treatment Emergent Adverse Events (TEAEs)

    Timeframe: Up to Week 55

    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.

  6. Number of participants with Adverse Events of Special Interest (AESIs)

    Timeframe: Up to Week 55

    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.

  7. Number of participants with laboratory value abnormalities and/or adverse events (AEs)

    Timeframe: Up to Week 55

    Number of participants with potentially clinically significant laboratory values.

  8. Number of participants with vital sign abnormalities and/or adverse events (AEs)

    Timeframe: Up to Week 55

    Number of participants with potentially clinically significant vital sign values.

  9. Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)

    Timeframe: Up to Week 52

    Number of participants with potentially clinically significant ECG values.

  10. 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

    Timeframe: Baseline and 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.

  11. 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

    Timeframe: Baseline and 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.

  12. 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

    Timeframe: Baseline and Weeks 1 to 3

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

  13. 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

    Timeframe: Baseline and Weeks 5 to 11

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

  14. Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline

    Timeframe: Baseline to Weeks 1, 4, 8 and 12

    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.

  15. Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline

    Timeframe: Baseline to Weeks 1, 4, 8 and 12

    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.

  16. Percent reduction at 100% in the frequency of moderate and severe VMS from baseline

    Timeframe: Baseline to Weeks 1, 4, 8 and 12

    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.

  17. Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen

    Timeframe: Up to Week 24

    CL/F will be derived using a population PK model.

  18. Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors

    Timeframe: Up to Week 24

    CL/F will be derived using a population PK model.

  19. PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen

    Timeframe: Up to Week 24

    Vc/F will be derived using a population PK model.

  20. PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors

    Timeframe: Up to Week 24

    Vc/F will be derived using a population PK model.

  21. PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen

    Timeframe: Up to Week 24

    Cavg will be derived using a population PK model.

  22. PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors

    Timeframe: Up to Week 24

    Cavg will be derived using a population PK model.

  23. PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen

    Timeframe: Up to Week 24

    Ctrough will be derived using a population PK model.

  24. PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors

    Timeframe: Up to Week 24

    Ctrough will be derived using a population PK model.

  25. PK of tamoxifen in Plasma: CL/F

    Timeframe: Up to Week 24

    CL/F will be derived using a population PK model.

And 30 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
Female
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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).

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Site CA15019Sarnia, Canada
  • Site CA15016Sault Ste. Marie, Canada
  • Site CA15002Montreal, Canada
  • Site CA15001Québec, Canada
  • Site CA15004Québec, Canada
  • Site CA15003Sherbrooke, Canada
  • Site CA15020Victoriaville, Canada
  • Site CA15007Trois-Rivières, Canada
  • Site CZ42006České Budějovice, Czechia
  • Site CZ42003Hořovice, Czechia
  • Site CZ42002Hradec Králové, Czechia
  • Site CZ42011Nový Jičín, Czechia
  • Site CZ42001Olomouc, Czechia
  • Site CZ42005Prague, Czechia
  • Site CZ42008Prague, Czechia
  • Site CZ42013Prague, Czechia
  • Site CZ42004Tábor, Czechia
  • Site CZ42007Vodňany, Czechia
  • Site CZ42009Vsetín, Czechia
  • Site DK45007Aalborg, Denmark
  • Site DE45003Esbjerg, Denmark
  • Site DK45009Hillerød, Denmark
  • Site DK45002Næstved, Denmark
  • Site DE45008Sønderborg, Denmark
  • Site FR33003Angers, France

And 85 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-510719-31-00
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Targets (4)