Fezolinetant for Hot Flashes in Breast Cancer

Recruiting at 138 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: Endocrine therapy

Must not be taking: Hormone therapy, CYP1A2 inhibitors

Disqualifiers: Metastatic cancer, Active liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 52 weeks

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fezolinetant as a new treatment for hot flashes in women undergoing hormone therapy for breast cancer. The researchers aim to determine if fezolinetant can reduce the number and severity of hot flashes compared to a placebo, which is a non-active pill resembling the medicine. Women experiencing at least seven moderate to severe hot flashes daily while receiving hormone therapy for non-metastatic breast cancer may qualify for this study. Participants will take either fezolinetant or a placebo daily for a year and will use a mobile app to track their symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires participants to continue their current hormone therapy for breast cancer without changes. However, you must stop any menopause hormone therapy, certain hormonal contraceptives, and treatments for hot flashes before joining the study.

Is there any evidence suggesting that fezolinetant is likely to be safe for humans?

Research has shown that fezolinetant is generally safe and effective for treating hot flashes. In earlier studies, participants taking fezolinetant experienced fewer and less intense hot flashes. The treatment also improved the quality of life for those undergoing menopause. Importantly, the FDA has approved fezolinetant for treating menopausal hot flashes, indicating its safety for this use. However, individual responses can vary. While most tolerate it well, some may experience side effects. Consulting a healthcare provider is essential to determine if it's suitable for individual needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hot flashes?

Fezolinetant is unique because it targets neurokinin 3 receptors, which play a key role in regulating body temperature and are thought to be involved in hot flashes. Unlike the standard treatments for hot flashes in breast cancer patients, which often involve hormone replacement therapies, fezolinetant works without affecting estrogen levels. This is particularly important for breast cancer patients, as hormone therapies can sometimes promote cancer growth. Researchers are excited about fezolinetant because it offers a non-hormonal approach to managing hot flashes, potentially providing relief without the risks associated with hormonal treatments.

What evidence suggests that fezolinetant might be an effective treatment for hot flashes in women undergoing hormone therapy for breast cancer?

Research has shown that fezolinetant, one of the treatments in this trial, can help reduce hot flashes. In studies, women taking fezolinetant experienced fewer and less intense hot flashes compared to those taking a placebo, which contains no active medicine. Participants in this trial will receive either fezolinetant or a placebo once daily for 52 weeks. One study found that hot flashes became less severe as soon as 12 weeks after starting the treatment. Fezolinetant works by blocking a chemical in the body that causes hot flashes. It is also well tolerated, meaning most people experience few side effects. This makes it a promising option for women undergoing hormone therapy for breast cancer who are dealing with hot flashes. ^{2 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

This trial is for women over 18 with breast cancer stages 0-3+, undergoing hormone therapy and experiencing at least 7 moderate to severe hot flashes daily. They must not be breastfeeding, expect to live at least another year, and agree to use contraception. Women cannot join if they are of childbearing potential or plan changes in their cancer treatment.

Inclusion Criteria

I had breast cancer stages 0-3 that was hormone receptor positive.

I have been on a stable breast cancer hormone treatment for at least 4 months and plan to continue.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fezolinetant or placebo once daily for 52 weeks to treat hot flashes

52 weeks

Visits every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

1 visit (in-person), 2 follow-up calls

Extension Follow-up

Participants continue to be monitored for long-term effects and safety until week 104

49 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fezolinetant

Trial Overview The study tests Fezolinetant's effectiveness against hot flashes compared to a placebo in women receiving hormone therapy for breast cancer. Participants will randomly receive either Fezolinetant or a placebo, without knowing which one, and take it daily for a year while tracking their symptoms.

How Is the Trial Designed?

Group I: Fezolinetant Experimental Treatment 3 Interventions

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.

Group II: Placebo Placebo Group 3 Interventions

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.

Fezolinetant is already approved in United States, European Union for the following indications:

Approved in United States as Veozah for:

• Moderate to severe vasomotor symptoms due to menopause

Approved in European Union as Veoza for:

• Hot flushes (vasomotor symptoms) associated with menopause

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Published Research Related to This Trial

Fezolinetant, a neurokinin 3 receptor antagonist, is being studied for its potential to treat moderate-to-severe menopausal symptoms, particularly vasomotor symptoms like hot flashes.

Recent research indicates that fezolinetant has shown promising safety and efficacy in alleviating these menopausal symptoms, suggesting it could be a valuable treatment option for women experiencing menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal. Gompel, A., Stuenkel, CA.[2023]

Aromatase inhibitors, a newer class of drugs for breast cancer treatment, offer a more selective option compared to traditional antiestrogens like tamoxifen, especially for menopausal women.

These inhibitors are effective in patients with tamoxifen-resistant metastatic cancer and are being explored as alternatives in first-line therapy and neoadjuvant settings, although further research is needed to address remaining questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aromatase inhibitors: therapeutic outlook]. Namer, M.[2009]

In a phase 2b study involving 352 menopausal women, fezolinetant, a selective neurokinin 3 receptor antagonist, significantly reduced the frequency and severity of moderate to severe vasomotor symptoms (VMS) compared to placebo, with reductions of up to 3.5 episodes per day at week 4.

Fezolinetant was well-tolerated, with mostly mild to moderate side effects and no serious treatment-related adverse events, making it a promising non-hormonal option for managing menopausal VMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Fraser, GL., Lederman, S., Waldbaum, A., et al.[2022]

Fezolinetant is a new oral medication that acts as a neurokinin 3 receptor (NK3R) antagonist, providing a non-hormonal approach to treat moderate to severe hot flashes associated with menopause.

It received its first approval in the USA in May 2023, marking a significant milestone in its development for managing vasomotor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fezolinetant: First Approval. Lee, A.[2023]

Menopausal hot flashes are common and can be very uncomfortable, but Menopausal Hormone Therapy (MHT) is effective in treating them, although it comes with risks that can limit its use.

Fezolinetant, a new nonhormonal treatment that works by blocking NK3 receptors, has recently been approved by the FDA as a promising alternative for managing menopausal hot flashes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonism for menopausal hot flashes. Comninos, AN., Dhillo, WS.[2023]

Fezolinetant effectively reduces the frequency and severity of vasomotor symptoms associated with menopause by inhibiting neurokinin B from binding to its receptor in the hypothalamus, as shown in clinical trials.

While fezolinetant is superior to placebo, common side effects include headaches, gastrointestinal issues, and elevated liver enzymes, providing a nonhormonal alternative for patients who may not tolerate hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms. Onge, ES., Phillips, B., Miller, L.[2023]

Letrozole, a third-generation aromatase inhibitor, has been shown to be more effective than tamoxifen and other treatments like megestrol acetate for advanced breast cancer in postmenopausal women, improving disease-free survival rates significantly.

In recent trials, letrozole demonstrated superior outcomes in both first-line and adjuvant settings, suggesting it may be a preferred option for treating hormone receptor-positive breast cancer, especially after initial tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. Mouridsen, HT., Bhatnagar, AS.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06440967

NCT06440967 | A Study to Confirm if Fezolinetant Helps ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10387909/

The effectiveness and value of fezolinetant for moderate- ... Participants treated with fezolinetant also had a significantly greater reduction in VMS severity at 12 weeks, exceeding the MCID for reduction in severity (> ...

3. breastcancer.org breastcancer.org/news/elinzanetant-veozah-reduce-hot-flashes

New Research on Hormone-Free Hot Flash Treatments Compared with women taking placebo, women who took elinzanetant reported less frequent and less severe hot flashes symptoms as early as week one ...

4. bmj.com bmj.com/content/387/bmj-2024-079525

Efficacy and safety of fezolinetant for moderate-severe ... Fezolinetant was efficacious and well tolerated over a six month period for treating moderate-severe vasomotor symptoms in individuals considered unsuitable ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06917313

FLASH-Breast: Evaluating the Efficacy of Fezolinetant in ... Investigators hypothesis is that neurokinin blockade by fezolinetant will significantly reduce vasomotor symptoms in breast cancer survivors on endocrine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12401328/

FDA approves Veozah (Fezolinetant) for menopausal symptoms Additionally, long-term safety data indicate a well-tolerated profile with ... Vasomotor symptoms, such as hot flashes and night sweats, significantly ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211524001921

Effectiveness and safety of fezolinetant in alleviating ... Fezolinetant significantly reduces frequency/severity of menopausal symptoms. · Fezolinetant enhances menopause-specific quality of life scores at 4/12 weeks, ...