Fezolinetant for Breast Cancer

Recruiting at 1 trial location

Overseen By Laura Kane

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Endocrine therapy

Must not be taking: CYP1A2 inhibitors

Disqualifiers: Stage IV cancer, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fezolinetant, a medication that might reduce hot flashes for breast cancer survivors on hormone therapy. The goal is to determine if fezolinetant is more effective than a placebo (a pill with no active ingredients). Postmenopausal women experiencing frequent, moderate to severe hot flashes while on tamoxifen or aromatase inhibitors might be suitable candidates. Participants must have been on their current therapy for at least three months and have at least 12 weeks remaining in their treatment plan. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop taking your current medications, but you must be on endocrine therapy (like tamoxifen or aromatase inhibitors) and not be receiving other cancer treatments or certain medications for hot flashes. It's best to discuss your specific medications with the trial team.

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

Research has shown that fezolinetant is generally safe for people and effective in reducing hot flashes during menopause. In terms of safety, no signs of tumor development have appeared in the two years since its approval. However, there is a possible risk of endometrial hyperplasia, where the lining of the uterus becomes too thick. This condition should be monitored, though recent studies have not reported any major safety concerns. Overall, fezolinetant appears safe for most people, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for breast cancer, which typically includes chemotherapy, hormone therapy, and targeted therapy, Fezolinetant offers a novel approach. This drug is unique because it is the first neurokinin 3 (NK3) receptor antagonist, specifically targeting the brain's regulation of body temperature. Researchers are excited about Fezolinetant because it was recently approved for managing menopause-related hot flashes, suggesting it could have a new and effective mechanism for addressing breast cancer symptoms linked to hormonal changes. Its distinct action on the NK3 receptor sets it apart from conventional treatments, potentially offering a new pathway to improve patient outcomes.

What evidence suggests that fezolinetant might be an effective treatment for vasomotor symptoms in breast cancer survivors?

Studies have shown that fezolinetant effectively treats moderate to severe hot flashes by blocking a specific receptor that helps control temperature. Earlier research found that patients taking fezolinetant experienced fewer hot flashes and reported an improved quality of life. This treatment was well tolerated, causing few side effects. The FDA has already approved fezolinetant for managing hot flashes due to menopause, supporting its potential use in breast cancer survivors with similar symptoms. In this trial, participants will receive either fezolinetant or a placebo to compare the effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Maryam Lustberg, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for women who have survived breast cancer and are currently on endocrine therapy (like tamoxifen or aromatase inhibitors). They should be experiencing moderate to severe hot flashes, also known as vasomotor symptoms.

Inclusion Criteria

I am a woman with early to mid-stage hormone-positive breast cancer.

Willing and able to provide written informed consent/assent for the trial

I am currently taking hormone therapy for cancer.

Exclusion Criteria

Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements

Pregnant or lactating patients

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive fezolinetant or placebo for 12 weeks to evaluate the reduction in vasomotor symptoms

12 weeks

Weekly data collection (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Crossover

Participants may choose to cross over to the other treatment arm after unblinding

What Are the Treatments Tested in This Trial?

Interventions

• Fezolinetant

Trial Overview The study is testing Fezolinetant, a new treatment given at 45 mg daily, against a placebo. It's designed to see if it helps reduce hot flashes in breast cancer survivors on hormone treatments. Participants will be randomly assigned to either the Fezolinetant group or the placebo group.

How Is the Trial Designed?

Group I: Fezolinetant Active Control 1 Intervention

Fezolinetant is an oral medication, and the first neurokinin 3 (NK3) receptor antagonist approved by the FDA in May 2023 for treatment of moderate to severe hot flashes due to menopause. It blocks the activities of the NK3 receptor which is involved in the brain's regulation of body temperature.

Group II: Placebo Placebo Group 1 Intervention

Patients will be given placebo tablets to compare to active comparator.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

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]

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]

In a study of 3,046 postmenopausal women with ductal carcinoma in situ, 28.5% discontinued treatment with anastrozole or tamoxifen, with specific adverse events like thrombosis and arthralgia linked to discontinuation of both drugs.

Patient-reported outcomes (PROs) such as pain interference and hot flashes were significant factors in discontinuing tamoxifen, while only hot flashes were associated with discontinuation of anastrozole, highlighting the importance of both adverse events and patient experiences in treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35. Henry, NL., Kim, S., Hays, RD., et al.[2023]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06617455

Study Details | NCT06617455 | Fezolinetant for the ... This phase II trial tests how well fezolinetant works in improving vasomotor symptoms (VMS) in breast cancer patients taking endocrine therapy (ET).

2. sciencedirect.com sciencedirect.com/science/article/pii/S0378512224002548

Effect of fezolinetant on patient-reported quality-of-life ... Fezolinetant was shown to be efficacious and well tolerated for treating moderate to severe VMS associated with menopause in phase 3 studies, SKYLIGHT 1 and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10727556/

Efficacy and safety of fezolinetant, a neurokinin-3 ... The efficacy outcomes in the meta-analysis include the improvement in terms of VMS frequency and severity scores along with MENQoL, HFRDIS, and ...

4. nejm.org nejm.org/doi/10.1056/NEJMoa2415566

Elinzanetant for Vasomotor Symptoms from Endocrine ... These symptoms affect quality of life and potentially lower long-term adherence to therapy, which results in poorer breast cancer outcomes.

5. esmo.org esmo.org/oncology-news/elinzanetant-leads-to-a-significantly-lower-frequency-of-vasomotor-symptoms-associated-with-endocrine-therapy-for-hr-positive-breast-cancer

Elinzanetant Leads To a Significantly Lower Frequency of ... Elinzanetant led to a significantly lower daily frequency of moderate-to-severe vasomotor symptoms, a greater decrease in sleep disturbances, and a greater ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12313727/

Safety of Fezolinetant for Treatment of Moderate-to-Severe ... No neoplasm signal with fezolinetant has been observed within the postmarketing setting over the last 2 years, and crucial safety monitoring is ...

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

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