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

Phase 3

Recruiting

• Conditions: Hot Flashes
• Interventions: Drug: Fezolinetant; Drug: Placebo; Drug: Tamoxifen; Drug: Aromatase inhibitor

• Registration Number: NCT06440967
• Lead Sponsor: Astellas Pharma Global Development, Inc.

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. Some women may be able to use the app on their own smartphone. In the last 10 days before their next clinic visit, the women will record information about their hot flashes. 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. This will include some blood and urine tests. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-29
• Study First Submitted QC: 2024-05-29
• Study First Posted: 2024-06-04
• Study Start: 2024-07-31
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26
• Primary Completion: 2026-10-31
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 540

Inclusion Criteria

• 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 (tamoxifen 20 mg daily or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. 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 study intervention administration.

• Female participant: Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 30 days after final study intervention administration.

• Female participant: Must not donate ova starting at first administration of study intervention and throughout the investigational period and for 30 days after final study intervention administration.

• Participant agrees not to participate in another interventional study while participating in the present study.

• Participant's condition is stable as determined on the basis of medical history and general physical examination (including a bimanual clinical pelvic examination devoid of relevant clinical findings performed at the screening visit), 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 or breast ultrasound). 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).

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Exclusion Criteria

• 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), elevated international normalized ratio (INR) 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 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fezolinetant	Fezolinetant	Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks.
Fezolinetant	Tamoxifen	Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks.
Fezolinetant	Aromatase inhibitor	Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks.
Placebo	Placebo	Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks.
Placebo	Tamoxifen	Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks.
Placebo	Aromatase inhibitor	Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS	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	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	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	Baseline to Week 12	The severity of VMS will be calculated using a weighted average of VMS events.

Secondary Outcome Measures

Name	Time	Method
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite endoxifen in Plasma: CL/F	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite endoxifen in Plasma: Cavg	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of aromatase inhibitors in Plasma: CL/F	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of aromatase inhibitors in Plasma: Vc/F	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of aromatase inhibitors in Plasma: Cavg	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
PK of aromatase inhibitors in Plasma: Ctrough	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of Fezolinetant in Plasma: Ctrough for participants taking tamoxifen	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of tamoxifen in Plasma: CL/F	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of tamoxifen in Plasma: Vc/F	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of tamoxifen in Plasma: Cavg	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
PK of tamoxifen in Plasma: Ctrough	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough	Up to Week 24	Ctrough will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score	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.
Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total Score	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).
Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS	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.
Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS	Baseline to Week 24	The severity of VMS will be calculated using a weighted average of VMS events.
Number of participants with Treatment Emergent Adverse Events (TEAEs)	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.
Number of participants with Adverse Events of Special Interest (AESIs)	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.
Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Up to Week 55	Number of participants with potentially clinically significant laboratory values.
Number of participants with vital sign abnormalities and/or adverse events (AEs)	Up to Week 55	Number of participants with potentially clinically significant vital sign values.
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)	Up to Week 52	Number of participants with potentially clinically significant ECG values.
Number of participants with mammogram or breast ultrasound abnormalities and/or adverse events (AEs)	Day 1	Number of participants with potentially clinically significant mammogram or breast ultrasound values.
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	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.
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	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.
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	Baseline and Weeks 1 to 3	The severity of VMS will be calculated using a weighted average of VMS events.
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	Baseline and Weeks 5 to 11	The severity of VMS will be calculated using a weighted average of VMS events.
Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline	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.
Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline	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.
Percent reduction at 100% in the frequency of moderate and severe VMS from baseline	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.
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F)	Up to Week 24	CL/F will be recorded from the PK plasma samples collected.
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F)	Up to Week 24	Vc/F will be recorded from the PK plasma samples collected.
PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen	Up to Week 24	Cavg will be recorded from the PK plasma samples collected.
Mean change from Baseline in the MENQOL Total Score	Baseline to Weeks 4, 8, 12 and 24	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.
Mean change from Baseline in the MENQOL VMS 1-week recall domain score	Baseline to Weeks 4, 8 and 24	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.
Mean change from Baseline in the MENQOL psychosocial 1-week recall domain score	Baseline to Weeks 4, 8, 12 and 24	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.
Mean change from Baseline in the MENQOL physical 1-week recall domain score	Baseline to Weeks 4, 8, 12 and 24	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.
Mean change from Baseline in the MENQOL sexual 1-week recall domain score	Baseline to Weeks 4, 8, 12 and 24	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.
Mean change from Baseline in the PROMIS SD SF 8b Total Score	Baseline to Weeks 4, 8 and 24	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).
Scores on the Patient Global Impression of Change (PGI-C) VMS	Up to Week 24	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.
Change from Baseline in the Patient Global Impression of Severity (PGI-S) VMS Score	Baseline to Weeks 4, 8, 12 and 24	The PGI-S VMS evaluates patient perceived severity of hot flashes/night sweats. Ratings range from (1) no problems to (4) severe problems.
Scores on the PGI-C sleep disturbance (SD)	Up to Week 24	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.
Change from Baseline in the PGI-S SD Score	Baseline to Weeks 4, 8, 12 and 24	The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems.

Trial Locations

Locations (3)

Site CA15002; 🇨🇦 Montreal, Quebec, Canada

Site CA15001; 🇨🇦 Quebec City, Quebec, Canada

Site CA15003; 🇨🇦 Sherbrooke, Quebec, Canada