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

Hot Flashes Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06440967
• Other study ID #: 2693-CL-1303
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 30, 2024
• Est. completion date: August 31, 2027

Study information

• Verified date: May 2024
• Source: Astellas Pharma Inc
• Contact: Astellas Pharma Global Development, Inc.
• Phone: 800-888-7704
• Email: Astellas.registration[@]astellas.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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 tests. Some visits will also include a bone scan (called a DXA scan) and a liver ultrasound. Women who have a womb (uterus) will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 540
• Est. completion date: August 31, 2027
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 has a body mass index (BMI) range of 18 kg/m2 to 38 kg/m2 inclusive at screening.

• 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 no clinically significant findings on a transvaginal ultrasound (TVU) result obtained within the last 3 months or at screening. Results indicate that the participant is a good candidate for the study. This is not required for participants who have had a partial (supra-cervical) or total hysterectomy.

• Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody screens).

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.

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• Fezolinetant
oral
• Placebo
oral
• Tamoxifen
oral
• Aromatase inhibitor
oral

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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.	Baseline to Week 12
Secondary	Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total 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).	Baseline to Week 12
Secondary	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	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.	Up to Week 55
Secondary	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.	Up to Week 55
Secondary	Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to Week 55
Secondary	Number of participants with vital sign abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to Week 55
Secondary	Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant ECG values.	Up to Week 52
Secondary	Number of participants with mammogram or breast ultrasound abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant mammogram or breast ultrasound values.	Day 1
Secondary	Number of participants with transvaginal ultrasound (TVU) abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant TVU values.	Up to Week 52
Secondary	Number of participants with dual-energy X-ray absorptiometry (DXA) abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant DXA values.	Up to Week 52
Secondary	Number of participants with liver ultrasound abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant liver ultrasound values.	Up to Week 52
Secondary	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.	Baseline and Weeks 1 to 3
Secondary	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.	Baseline and Weeks 5 to 11
Secondary	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.	Baseline and Weeks 1 to 3
Secondary	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.	Baseline and Weeks 5 to 11
Secondary	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.	Baseline to Weeks 1, 4, 8 and 12
Secondary	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.	Baseline to Weeks 1, 4, 8 and 12
Secondary	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.	Baseline to Weeks 1, 4, 8 and 12
Secondary	Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F)	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F)	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of Fezolinetant in Plasma: Ctrough for participants taking tamoxifen	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen in Plasma: CL/F	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen in Plasma: Vc/F	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen in Plasma: Cavg	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen in Plasma: Ctrough	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite endoxifen in Plasma: CL/F	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite endoxifen in Plasma: Cavg	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of aromatase inhibitors in Plasma: CL/F	CL/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of aromatase inhibitors in Plasma: Vc/F	Vc/F will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of aromatase inhibitors in Plasma: Cavg	Cavg will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	PK of aromatase inhibitors in Plasma: Ctrough	Ctrough will be recorded from the PK plasma samples collected.	Up to Week 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24
Secondary	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.	Baseline to Weeks 4, 8 and 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24
Secondary	Mean change from Baseline in the PROMIS SD SF 8b Total 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).	Baseline to Weeks 4, 8 and 24
Secondary	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.	Up to Week 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24
Secondary	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.	Up to Week 24
Secondary	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.	Baseline to Weeks 4, 8, 12 and 24