Fulvestrant + Binimetinib for Breast Cancer

Recruiting at 220 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding binimetinib to the usual treatment of fulvestrant can help patients with a specific type of advanced breast cancer. Fulvestrant works by blocking estrogen receptors on cancer cells, while binimetinib stops enzymes that help cancer grow. The goal is to see if this combination can better control the cancer compared to using fulvestrant alone.

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.

What data supports the idea that Fulvestrant + Binimetinib for Breast Cancer is an effective treatment?

The available research shows that Fulvestrant is effective in treating advanced breast cancer, especially in postmenopausal women. It has been compared to other drugs like anastrozole and tamoxifen, showing similar or better results in patients whose cancer progressed after previous treatments. Although the research does not specifically mention Binimetinib, Fulvestrant alone has demonstrated positive outcomes in clinical trials, suggesting its potential effectiveness when combined with other treatments. ^{1 2 3 4 5}

What safety data is available for the treatment of Fulvestrant and Binimetinib in 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 studies, including the Compassionate Use Program and clinical trials, adverse events leading to discontinuation were low, with only 1.5% to 5% of patients discontinuing due to adverse effects. Fulvestrant has been used effectively as a first to sixth-line treatment, with a clinical benefit rate ranging from 27% to 46% depending on the line of treatment. However, specific safety data for the combination of Fulvestrant and Binimetinib is not provided in the available research. ^{1 4 6 7 8}

Is the drug Fulvestrant (Faslodex) a promising treatment for breast cancer?

Yes, Fulvestrant (Faslodex) is a promising drug for treating breast cancer. It has shown effectiveness in patients with advanced breast cancer, especially those who have already tried other treatments. It works by blocking estrogen, which can help slow down or stop the growth of cancer cells. Many patients have experienced stable disease for several months, and it is well-tolerated with few side effects. ^{4 5 6 9 10}

Research Team

Bora Lim

Principal Investigator

CenterThe University of Texas MD Anderson Cancer Center

Eligibility Criteria

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.

Treatment Details

Interventions

• Binimetinib (MEK Inhibitor)
• Fulvestrant (Hormone Therapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

References

1. United States 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. [2022]

2. Japan 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. [2020]

3. United States 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. [2022]

4. United States 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. [2022]

5. Netherlands 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. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. [2018]

7. England 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. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]

10. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: fulvestrant. [2019]