Fezolinetant for Breast Cancer

(VEnT Trial)

Overseen By Cancer AnswerLine

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Endocrine therapy

Must not be taking: CYP1A2 inhibitors, Estrogen products

Disqualifiers: Metastatic cancer, Severe renal disease, Cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 10 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fezolinetant, a new potential drug, can reduce uncomfortable hot flashes and night sweats in women with breast cancer undergoing hormone therapy. These symptoms, known as vasomotor symptoms, are common and bothersome side effects of cancer treatment. Participants will take either fezolinetant or a placebo for a set period, then switch, allowing researchers to compare the effects. Women on endocrine therapy for stage 1-3 breast cancer who frequently experience severe or bothersome hot flashes may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are taking certain medications like SSRIs, SNRIs, gabapentinoids, clonidine, or oxybutynin, you must have been on a stable dose for at least 30 days before joining the study and continue them during the study. If you plan to stop these medications, you should do so at least 7 days before the screening period. Over-the-counter supplements or herbal medications for VMS should also be stopped at least 7 days before the screening period.

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

Research has shown that fezolinetant is well-tolerated in past studies. In one study, patients used fezolinetant for six months to treat moderate to severe hot flashes, and it proved both effective and well-tolerated. Another study found that a 30 mg daily dose effectively reduced the number and intensity of these symptoms in postmenopausal women.

Although specific safety information for fezolinetant in breast cancer patients is limited, its use in other groups suggests it is generally safe and well-tolerated. This phase of the trial aims to confirm its safety specifically for breast cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Most treatments for breast cancer, like chemotherapy and hormone therapy, work by attacking cancer cells directly or altering hormone levels. But fezolinetant works differently, targeting neurokinin-3 receptors, which are involved in the body's temperature regulation and other functions. Researchers are excited about fezolinetant because it offers a new mechanism of action that could potentially reduce symptoms and improve quality of life for patients, especially those experiencing issues like hot flashes due to hormone therapy. This unique approach makes fezolinetant a promising addition to breast cancer care.

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

Research has shown that fezolinetant reduces symptoms like hot flashes and night sweats, particularly in postmenopausal women. Participants taking fezolinetant reported a significant decrease in symptom severity, indicating a substantial improvement in their condition. Most did not experience adverse side effects, making fezolinetant a promising option for those managing these symptoms during breast cancer hormone therapy. In this trial, one study arm will receive fezolinetant, while the other will begin with a placebo before switching to fezolinetant. ^{2 5 6 7 8}

Who Is on the Research Team?

Norah L. Henry

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for breast cancer patients experiencing hot flashes and night sweats due to endocrine therapy. Participants should be currently receiving anti-hormone treatments for breast cancer.

Inclusion Criteria

I plan to continue my current hormone therapy for at least 10 weeks after starting the study drug.

Able to self-complete questionnaires in English

I am a woman aged 18 or older.

Exclusion Criteria

I have previously been treated with fezolinetant.

I have been diagnosed with cirrhosis.

Pregnant or breast feeding, or plan to become pregnant during the study period or within 3 months of completing study medication

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 for 28 days, followed by a 14-day washout period, then crossover to the alternate treatment for another 28 days

10 weeks

Regular visits for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fezolinetant

Trial Overview The VENT trial is testing fezolinetant, a drug that may reduce vasomotor symptoms like hot flashes in those on endocrine therapy for breast cancer. It's compared with a placebo while monitoring quality of life through questionnaires and collecting biospecimens.

How Is the Trial Designed?

Group I: Arm II (placebo, fezolinetant) Experimental Treatment 5 Interventions

Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.

Group II: Arm I (fezolinetant, placebo) Experimental Treatment 5 Interventions

Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.

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?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

The Breast Cancer Research Foundation

Collaborator

Trials

2

Recruited

50+

Published Research Related to This Trial

Vorozole, a non-steroidal aromatase inhibitor, significantly reduced the size of mammary tumors in female Sprague-Dawley rats over a 28-day treatment period, demonstrating its potential efficacy in tumor regression.

The treatment also led to a dose-dependent decrease in tissue insulin-like growth factor I (IGF-I) levels in the tumors, suggesting a mechanism of action that may involve the modulation of growth factors associated with tumor development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel aromatase inhibitor, vorozole, shows antitumor activity and a decrease of tissue insulin-like growth factor-I level in 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumors. Sugamata, N., Koibuchi, Y., Iino, Y., et al.[2014]

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]

Arzoxifene, a selective estrogen receptor modulator, effectively inhibited the repopulation of estrogen-dependent MCF-7 breast cancer cells in xenografts when administered between chemotherapy cycles, leading to a significant delay in tumor development.

When combined with standard chemotherapy agents like 5-fluorouracil or paclitaxel, arzoxifene substantially reduced tumor incidence, suggesting that using short-acting hormonal agents in treatment schedules could enhance the effectiveness of breast cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the selective estrogen receptor modulator arzoxifene on repopulation of hormone-responsive breast cancer xenografts between courses of chemotherapy. Wu, L., Tannock, IF.[2022]

In a study of 147 postmenopausal women with advanced breast cancer resistant to standard treatments, 22% experienced a partial response to the aromatase inhibitor formestane, while 20% had stabilization of their disease.

Formestane demonstrated effectiveness regardless of previous responses to other therapies, and it was associated with minimal toxicity, making it a promising treatment option for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced breast cancer with formestane. Murray, R., Pitt, P.[2016]

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, 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]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

Vorozole effectively reduces plasma estradiol levels by about 90% in postmenopausal women and has shown objective responses in up to 35% of patients with advanced breast cancer in Phase II clinical studies.

In Phase III studies, vorozole demonstrated better clinical efficacy and improved quality of life compared to aminoglutethimide, with a better tolerability profile than both aminoglutethimide and megestrol, although mild side effects like hot flushes and nausea were common.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vorozole. Wiseman, LR., Spencer, CM.[2018]

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. 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. 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 ...

4. 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 ...

5. 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 Veozah had less frequent and less severe hot flashes during the 24 weeks. Women taking Veozah ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12184116/

Efficacy and safety of fezolinetant for vasomotor symptoms in ... In conclusion, fezolinetant, especially at a 30 mg daily dose, effectively reduced the frequency and severity of VMS in postmenopausal women.

7. 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).

8. contemporaryobgyn.net contemporaryobgyn.net/view/first-patient-dosed-in-trial-evaluating-fezolinetant-for-vms-in-breast-cancer-patients

First patient dosed in trial evaluating fezolinetant for VMS ... Currently, safety and efficacy data for fezolinetant in breast cancer patients with moderate to severe VMS is not well-established.