What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as Selective Estrogen Receptor Degraders (SERDs) like Elacestrant and CDK4/6 inhibitors like Abemaciclib, have specific side effects. SERDs can cause hot flashes, fatigue, and gastrointestinal issues. CDK4/6 inhibitors are known to cause neutropenia, diarrhea, fatigue, and nausea. Additionally, both types of treatments may lead to liver function abnormalities and increased risk of infections. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

FDA approvals for brain tumor treatments have included various chemotherapeutic agents, targeted therapies, and immunotherapies. While specific approvals for SERDs like Elacestrant and CDK4/6 inhibitors like Abemaciclib in brain tumors are limited, other targeted therapies such as bevacizumab (an anti-VEGF antibody) have been approved for glioblastoma. Additionally, temozolomide, an oral alkylating agent, is widely used in combination with radiotherapy for glioblastoma treatment. These therapies focus on disrupting tumor growth and proliferation through different mechanisms, similar to the approach of targeting estrogen receptors and cell cycle pathways in other cancers.

What other types of research exist?

Promising novel alternatives for brain tumor patients in 2024 include: 1) Lorlatinib, which has shown brain penetration and efficacy in ALK-positive non-small cell lung cancer with brain metastases. 2) Osimertinib, which improves overall survival in EGFR-mutated NSCLC with leptomeningeal metastases. 3) Nivolumab and Pembrolizumab, immune checkpoint inhibitors that have demonstrated intracranial responses in various studies. 4) Lutetium-177-PSMA-617, a radioligand therapy for metastatic castration-resistant prostate cancer with potential applications in brain metastases.

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CDK4/6 Inhibitor

Abemaciclib + Elacestrant for Brain Metastasis from Breast Cancer (ELECTRA Trial)

Q: What is the mechanism of action of this treatment?

Elacestrant, a Selective Estrogen Receptor Degrader (SERD), works by binding to estrogen receptors and promoting their degradation, thereby inhibiting estrogen-driven tumor growth. Abemaciclib, a CDK4/6 inhibitor, blocks cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression, thus preventing tumor cell proliferation. These targeted mechanisms are significant for brain tumor patients as they offer more effective and personalized treatment options, potentially improving outcomes by specifically halting tumor growth and proliferation.

Phase 1 & 2

Recruiting

Research Sponsored by Stemline Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Patient has adequate bone marrow and organ function, as defined by the following laboratory values: Absolute neutrophil count (ANC) ≥1.5 × 109/L, Platelets ≥100 × 109/L, Hemoglobin ≥9.0 g/dL, Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE Grade ≤1 (if screening assessments are abnormal, these assessments may be repeated up to 2 times; subjects may receive appropriate supplementation or treatment prior to reassessment), Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL/min, Serum albumin ≥3.0 g/dL (≥30 g/L), In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN. If the patient has liver metastases, ALT and AST ≤5 × ULN, Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN, The patient is able and willing to adhere to the study visit schedule and other protocol requirements

Patient must have ER-positive, HER-2 negative tumor status as confirmed by local laboratory testing either from a fresh biopsy or from an archival tissue obtained no more than 2 years prior to signing of the informed consent form. ER and HER-2 testing must be performed in the following manner: Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry (IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology (ASCO) recommendations for ER testing, with or without progesterone receptor (PGR) positivity, HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane protein expression or an in situ hybridization negative result as defined in the 2013 or 2018 ASCO recommendations for HER-2 testing

Must not have

Prior therapy with elacestrant or other investigational SERDs, or alike agents such as SERMs, SERCANs, CERANs, and PROTACs in the metastatic setting

Uncontrolled significant active infections

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

Summary

This trial tests a combination of two drugs, elacestrant and abemaciclib, in patients with a specific type of breast cancer. It aims to find the best dose and see how well it works for those whose cancer has spread to the brain. The drugs work by blocking signals that help cancer cells grow and divide. Abemaciclib is a drug that has been approved for the treatment of certain advanced breast cancers.

Who is the study for?

This trial is for men and women over 18 with brain metastases from ER-positive, HER-2 negative breast cancer. They must have had prior treatments including endocrine therapy and chemotherapy, be stable neurologically for at least 2 weeks, and not be breastfeeding or pregnant. Participants need to have good organ function and performance status, cannot have leptomeningeal metastases or imminent organ failure, and must agree to use effective contraception.

What is being tested?

The study is testing the combination of two drugs: Elacestrant and Abemaciclib in patients with brain metastasis due to hormone receptor-positive (HR+)/HER2-negative breast cancer. It's an open-label global study that will first determine the best dose (Phase 1b) followed by a larger test of effectiveness (Phase 2).

What are the potential side effects?

Potential side effects may include fatigue, nausea, diarrhea, low blood cell counts leading to increased infection risk or bleeding problems. Liver function abnormalities could occur as well as potential harm to unborn babies; hence contraception is required.

Eligibility Criteria

Inclusion Criteria

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

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Your blood, bone marrow, and organ functions are within normal range, and you are able and willing to attend all study appointments and follow the study's instructions.

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My cancer is ER-positive and HER-2 negative, confirmed by a test within the last 2 years.

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I can take care of myself but might not be able to do heavy physical work.

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My cancer has worsened or returned after my last treatment.

Exclusion Criteria

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

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I have not taken elacestrant or similar drugs for my cancer.

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I do not have any severe ongoing infections.

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I have not had major surgery in the last 4 weeks.

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I am not pregnant or breastfeeding.

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My cancer has spread to the lining of my brain and spinal cord.

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I am experiencing a severe health crisis due to organ failure.

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I cannot take pills by mouth or have a condition that affects how my body absorbs food.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 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)

Recommended phase 2 dose (RP2D)

Secondary study objectives

Clinical Benefit Rate (CBR)

Duration of Tumor Response (DOR)

Intracranial RR per Response Assessment in Neuro-Oncology (RANO)

+2 more

Trial Design

4Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment2 Interventions

Elacestrant in combination with abemaciclib at the recommended phase 2 dose (RP2D) determined in phase 1b

Group II: Phase 1b Cohort 3Experimental Treatment2 Interventions

Elacestrant 400 mg QD + abemaciclib 150 mg BID

Group III: Phase 1b Cohort 2Experimental Treatment2 Interventions

Elacestrant 400 mg QD + abemaciclib 100 mg BID

Group IV: Phase 1b Cohort 1Experimental Treatment2 Interventions

Elacestrant 300 mg once daily (QD) + abemaciclib 100 mg twice daily (BID)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Elacestrant

2015

Completed Phase 1

~80

Abemaciclib

2019

Completed Phase 2

~1800

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

Elacestrant, a Selective Estrogen Receptor Degrader (SERD), works by binding to estrogen receptors and promoting their degradation, thereby inhibiting estrogen-driven tumor growth. Abemaciclib, a CDK4/6 inhibitor, blocks cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression, thus preventing tumor cell proliferation. These targeted mechanisms are significant for brain tumor patients as they offer more effective and personalized treatment options, potentially improving outcomes by specifically halting tumor growth and proliferation.

Inhibition of Rb and mTOR signaling associates with synergistic anticancer effect of palbociclib and erlotinib in glioblastoma cells.Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.