Fulvestrant + Binimetinib for Breast Cancer

No longer recruiting at 227 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: CDK4/6 inhibitors

Must not be taking: Systemic steroids

Disqualifiers: Autoimmune disease, Brain metastasis, Cardiac disease, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding binimetinib to the standard breast cancer treatment, fulvestrant, benefits patients with hormone receptor-positive breast cancer that has spread and has an NF1 genetic change. Fulvestrant targets estrogen receptors in cancer cells, while binimetinib blocks enzymes necessary for cancer cell growth. The trial seeks to increase the number of tumors that shrink and extend the time they remain stable. It may suit those with hormone receptor-positive breast cancer that has spread, an NF1 genetic change, and prior use of a CDK4/6 inhibitor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, concurrent anticancer therapy is not allowed, so you may need to stop any current cancer treatments. Please consult with the trial team for specific guidance on your medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fulvestrant, a treatment for advanced breast cancer, is usually well tolerated. While most patients manage it well, some may experience side effects like nausea and tiredness. Studies have found that adding binimetinib to cancer treatments can cause side effects such as skin rash or diarrhea, but these are generally manageable. Researchers are still studying the combination of fulvestrant and binimetinib, and early results suggest it might be safe for most people. However, since the trial is in an early stage, more research is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine fulvestrant, a hormone therapy that blocks estrogen receptors, with binimetinib, a MEK inhibitor that targets a different pathway involved in cancer cell growth. Unlike traditional treatments that mainly focus on hormonal pathways, this combination therapy offers a dual approach, potentially tackling the cancer more effectively. The addition of binimetinib is particularly intriguing because it targets the MEK/ERK pathway, which is often overactive in breast cancer, giving it a potential edge over standard hormone therapies alone. By addressing multiple pathways, this combo may offer a more comprehensive treatment option for patients with breast cancer.

What evidence suggests that this trial's treatments could be effective for metastatic hormone receptor positive breast cancer with an NF1 genetic change?

This trial will compare the effectiveness of fulvestrant alone versus the combination of fulvestrant and binimetinib for breast cancer patients with a specific NF1 genetic change. Research has shown that adding binimetinib to fulvestrant might be more effective than using fulvestrant alone. Fulvestrant works by breaking down estrogen receptors in cancer cells, slowing their growth. However, some patients may eventually stop responding to fulvestrant. Binimetinib is a targeted treatment that blocks certain enzymes cancer cells need to grow, potentially aiding when fulvestrant becomes less effective. Early evidence suggests that combining both treatments may shrink more tumors and inhibit cancer growth longer than fulvestrant alone. ^{1 2 3 5 6}

Who Is on the Research Team?

Bora Lim

Principal Investigator

CenterThe University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with hormone receptor-positive metastatic breast cancer that has an NF1 genetic change. Participants must have had prior treatment with fulvestrant, can have one chemotherapy line in the metastatic setting, and need to be able to undergo a biopsy. They should not be pregnant, have untreated brain metastasis, severe autoimmune diseases, or any condition that could affect the study's safety.

Inclusion Criteria

I have been active and mostly self-sufficient in the last 2 weeks.

My tumor is positive for estrogen or progesterone receptors.

I have had only one chemotherapy treatment for my cancer after it spread.

Exclusion Criteria

My brain metastasis has been stable for at least 1 month after treatment.

I am not currently receiving any cancer treatments.

You have factors that increase the chance of developing a retinal vein occlusion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive fulvestrant and binimetinib in cycles of 28 days, with regular imaging and biopsies

Up to 5 years

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Fulvestrant

Trial Overview The study compares standard hormonal therapy (fulvestrant) alone versus combining it with binimetinib—a drug targeting enzymes involved in cell growth—in patients whose tumors carry an NF1 mutation. The goal is to see if adding binimetinib improves tumor shrinkage and delays progression compared to fulvestrant alone.

How Is the Trial Designed?

Group I: Cohort II (fulvestrant, binimetinib) Experimental Treatment 9 Interventions

Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group II: Cohort I (Arm I) (fulvestrant, binimetinib) Experimental Treatment 9 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group III: Cohort I (Arm II) Active Control 8 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

In the phase III FALCON trial involving 462 postmenopausal women with hormone receptor-positive breast cancer, fulvestrant 500 mg showed improved progression-free survival compared to anastrozole 1 mg, indicating its efficacy as a treatment option.

Both fulvestrant and anastrozole maintained overall health-related quality of life (HRQoL) during treatment, with similar proportions of patients reporting improvements in their quality of life, suggesting that fulvestrant is not only effective but also well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life from the FALCON phase III randomised trial of fulvestrant 500 mg versus anastrozole for hormone receptor-positive advanced breast cancer. Robertson, JFR., Cheung, KL., Noguchi, S., et al.[2019]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

Fulvestrant 500 mg significantly improves the clinical benefit rate (CBR) in postmenopausal women with hormone receptor-positive advanced breast cancer compared to other endocrine therapies, based on a meta-analysis of six randomized controlled trials involving 1588 patients.

The analysis showed that fulvestrant 500 mg was particularly effective as a first-line treatment, with a notable odds ratio of 1.33 indicating a higher proportion of patients achieving a complete or partial response or stable disease for at least 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. Robertson, JFR., Jiang, Z., Di Leo, A., et al.[2020]

Fulvestrant is an effective treatment for postmenopausal women with hormone-sensitive metastatic breast cancer, showing similar response rates to anastrozole in two phase III studies involving 851 participants, with 17-20% response rates for fulvestrant compared to 15-17% for anastrozole.

The most common side effects of fulvestrant include injection-site reactions and hot flashes, with no significant differences in safety profiles between fulvestrant and anastrozole, leading to its FDA approval for patients who have progressed after tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: fulvestrant. Bross, PF., Cohen, MH., Williams, GA., et al.[2019]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

In a study involving 451 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in terms of time to progression, with median times of 5.5 months for fulvestrant and 5.1 months for anastrozole.

Both treatments were well tolerated, with low withdrawal rates due to adverse events (3.2% for fulvestrant and 1.3% for anastrozole), indicating that fulvestrant is a safe and effective option for patients who have progressed on prior endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Howell, A., Robertson, JF., Quaresma Albano, J., et al.[2022]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

In a study of 400 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in delaying disease progression, with a median time to progression of 5.4 months for fulvestrant compared to 3.4 months for anastrozole.

Fulvestrant also demonstrated a significantly longer duration of response in patients who responded to treatment, with a median duration of 19.0 months compared to 10.8 months for anastrozole, indicating it may provide a more sustained benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. Osborne, CK., Pippen, J., Jones, SE., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05554354

NCT05554354 | Testing the Use of Fulvestrant and ... The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen ...

2. nrgoncology.org nrgoncology.org/Home/News/Post/fulvestrant-and-binimetinib-targeted-treatment-for-nf1-mutation-in-hormone-receptor-positive-metastatic-breast-cancer-eay191-n2-a-combomatch-treatment-trial

Fulvestrant and Binimetinib Targeted Treatment for NF1 ... The agent fulvestrant has exhibited initial efficacy in NF1 lost ER+ breast cancer, however, typically results in eventual resistance from the ...

3. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf17/P170019S048B.pdf

Summary of Safety and Effectiveness Data (SSED) The effectiveness of F1CDx to identify breast cancer patients with AKT1, PIK3CA, and PTEN alterations who may experience increased benefit from ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8391338/

Efficacy of Fulvestrant in Women with Hormone-Resistant ... Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival ...

5. cancer.gov cancer.gov/news-events/press-releases/2023/combomatch-precision-medicine-cancer-initiative

ComboMATCH will test new combinations of cancer drugs A study testing the use of fulvestrant (Faslodex) and binimetinib (Mektovi) in patients with an NF1 mutation in hormone receptor-positive breast ...

6. withpower.com withpower.com/trial/phase-2-carcinoma-11-2022-54da8

Fulvestrant + Binimetinib for Breast Cancer The safety data for Fulvestrant, also known as Faslodex, indicates that it is generally well tolerated in the treatment of advanced breast cancer. In various ...