What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as the combination of Binimetinib (a targeted enzyme inhibitor) and Fulvestrant (an estrogen receptor destructor), have specific side effects. Binimetinib often causes rash and nausea, with rare severe reactions. Fulvestrant can lead to injection site pain, nausea, and fatigue. When combined, these treatments may have overlapping toxicities, requiring careful monitoring and management of side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that involve targeted enzyme inhibition and estrogen receptor destruction. Fulvestrant, an estrogen receptor antagonist, is commonly used in hormone receptor-positive metastatic breast cancer. It works by binding to estrogen receptors and promoting their degradation. In combination with targeted therapies, such as CDK 4/6 inhibitors (e.g., ribociclib, palbociclib, and abemaciclib), Fulvestrant has shown improved efficacy. These CDK 4/6 inhibitors work by inhibiting enzymes crucial for cell cycle progression, thereby enhancing the anti-tumor effects of Fulvestrant. Additionally, the PI3K inhibitor alpelisib has been approved for use with Fulvestrant in cases with PIK3CA mutations, further exemplifying the strategy of combining targeted enzyme inhibition with estrogen receptor destruction.

What other types of research exist?

Promising alternatives to Binimetinib and Fulvestrant for breast cancer treatment include: 1) Palbociclib in combination with Fulvestrant, which has shown efficacy in hormone receptor-positive, HER2-negative advanced breast cancer. 2) Trastuzumab deruxtecan, an antibody-drug conjugate for HER2-overexpressing metastatic breast cancer. 3) Pembrolizumab plus cetuximab, being investigated for treatment-refractory metastatic breast cancer. 4) Novel agents targeting specific genetic mutations such as HER2 exon 20 insertions (e.g., Poziotinib) and RET fusion-positive tumors (e.g., Selpercatinib).

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Hormone Therapy

Fulvestrant + Binimetinib for Breast Cancer

Phase 2

Recruiting

Led By Bora Lim

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 14 days prior to registration

The tumor must have been determined to be estrogen receptor (ER) and/or progesterone receptor (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing

Must not have

Concurrent anticancer therapy

History of or evidence of specific retinal pathology

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Fulvestrant may cause injection site reactions, nausea, and fatigue. Binimetinib might lead to skin rash, high blood pressure, muscle pain or weakness; it also carries risks of eye problems like blurred vision or retinal vein occlusion.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My tumor is positive for estrogen or progesterone receptors.

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My cancer has spread, confirmed by scans or biopsy.

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I have previously been treated with a CDK4/6 inhibitor.

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My breast cancer diagnosis was confirmed through tissue examination.

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I am 18 years old or older.

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I have a tumor that can be measured and another that can be biopsied.

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My tumor has a specific genetic change called NF1 mutation.

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My tumor is not HER2 positive according to specific guidelines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not currently receiving any cancer treatments.

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I have a history of specific eye retina problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR) (Cohort II)

Progression free survival (PFS) (Cohort I)

Secondary study objectives

Clinical benefit rate

Incidence of adverse events

ORR (Cohort II)

+3 more

Other study objectives

Analysis of integrated and exploratory biomarkers

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Cohort II (fulvestrant, binimetinib)Experimental Treatment9 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 Treatment9 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 Control8 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Computed Tomography

2017

Completed Phase 2

~2790

Echocardiography

2013

Completed Phase 4

~11580

Bone Scan

2015

Completed Phase 2

~50

Biopsy

2014

Completed Phase 4

~1150

Biospecimen Collection

2004

Completed Phase 3

~2030

Fulvestrant

2011

Completed Phase 3

~3790

Binimetinib

2018

Completed Phase 3

~1250

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Multigated Acquisition Scan

2015

Completed Phase 3

~270

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific mechanisms to inhibit tumor growth. Fulvestrant works by binding to estrogen receptors on tumor cells, leading to their destruction and reducing estrogen binding, which is crucial for the growth of estrogen-sensitive tumors. Binimetinib, a targeted therapy, inhibits specific enzymes necessary for cell growth, thereby halting tumor progression. These mechanisms are vital for breast cancer patients as they offer targeted approaches that can be more effective and have fewer side effects compared to traditional chemotherapy. Other common treatments include CDK4/6 inhibitors, which block proteins involved in cell division, and HER2 inhibitors, which target the HER2 protein overexpressed in some breast cancers. Understanding these mechanisms helps in personalizing treatment plans, improving outcomes, and managing resistance to therapies.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.An evidence-based review of the outcome of fulvestrant plus a targeted agent versus fulvestrant alone in treating hormone receptor-positive endocrine therapy-resistant metastatic breast cancer.ErbB family receptor inhibitors as therapeutic agents in breast cancer: current status and future clinical perspective.