Abemaciclib + Elacestrant for Brain Metastasis from Breast Cancer

(ELECTRA Trial)

Recruiting at 91 trial locations

Overseen By Mary Ann Samparani

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stemline Therapeutics, Inc.

Must not be taking: CYP3A4 inducers/inhibitors, Herbal meds

Disqualifiers: Leptomeningeal metastases, Concurrent malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

68 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take certain medications like strong or moderate inducers or inhibitors of CYP3A4, some herbal preparations, or receive vaccinations within specific timeframes before starting the trial.

What data supports the effectiveness of the drug Abemaciclib for treating brain metastasis from breast cancer?

Research shows that Abemaciclib is effective in treating hormone receptor-positive breast cancer, including cases with brain metastases, by improving progression-free survival and reducing the risk of cancer recurrence when combined with endocrine therapy. ^{1 2 3 4 5}

Is the combination of Abemaciclib and Elacestrant safe for treating brain metastasis from breast cancer?

Abemaciclib has been studied for safety in various breast cancer treatments, showing manageable side effects like diarrhea, infections, and low white blood cell counts. While specific safety data for the combination with Elacestrant in brain metastasis is not detailed, Abemaciclib alone has an acceptable safety profile in other breast cancer contexts. ^{1 3 4 5 6}

How is the drug Abemaciclib + Elacestrant unique for treating brain metastasis from breast cancer?

This treatment is unique because it combines Abemaciclib, a CDK4/6 inhibitor that targets specific proteins to stop cancer cell growth, with Elacestrant, a selective estrogen receptor degrader, potentially offering a novel approach for patients with brain metastases from hormone receptor-positive breast cancer, where standard treatments are limited. ^{2 3 4 5 7}

Eligibility Criteria

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.

Inclusion Criteria

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.

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

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

Exclusion Criteria

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

Patients currently receiving or received any of the following medications prior to first dose of trial therapy: Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 21 days prior to initiating trial therapy, Herbal preparations/medications, Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization, Any severe medical or psychiatric condition that in the opinion of the investigator(s) would preclude the patient's participation in a clinical study

I have metastatic breast cancer and haven't received treatment, or it recurred within 12 months after my last treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Evaluation of elacestrant in combination with abemaciclib to select the recommended phase 2 dose

1 year

Regular visits for dose-limiting toxicity evaluation

Phase 2 Treatment

Ongoing evaluation of elacestrant in combination with abemaciclib at the recommended phase 2 dose

3 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Abemaciclib
• Elacestrant

Trial Overview 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).

Participant Groups

Group I: Phase 2 Experimental Treatment 2 Interventions

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

Group II: Phase 1b Cohort 3 Experimental Treatment 2 Interventions

Elacestrant 400 mg QD + abemaciclib 150 mg BID

Group III: Phase 1b Cohort 2 Experimental Treatment 2 Interventions

Elacestrant 400 mg QD + abemaciclib 100 mg BID

Group IV: Phase 1b Cohort 1 Experimental Treatment 2 Interventions

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

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Findings from Research

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

In a retrospective study of 69 female patients with hormone receptor-positive, HER2-negative metastatic breast cancer, abemaciclib demonstrated effectiveness as both a monotherapy and in combination with endocrine therapy, aligning with previous clinical trial results.

The median duration of abemaciclib treatment was 7.7 months, with 86% of patients discontinuing treatment mainly due to disease progression, indicating that while effective, the drug is often used in heavily pretreated patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS). Blanch, S., Gil-Gil, JM., Arumí, M., et al.[2023]

In a phase II study involving patients with hormone receptor-positive metastatic breast cancer and brain or leptomeningeal metastases, abemaciclib showed an intracranial clinical benefit rate of 24% in cohort A (n=58), indicating some effectiveness in this heavily pretreated group.

Abemaciclib achieved significantly high concentrations in brain metastases tissue, exceeding the levels needed for effective inhibition of CDK4 and CDK6, suggesting potential for further exploration of this treatment in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. Tolaney, SM., Sahebjam, S., Le Rhun, E., et al.[2021]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

In the phase II MONARCH 1 study involving 132 women with refractory hormone receptor-positive, HER2-negative metastatic breast cancer, abemaciclib showed a confirmed objective response rate of 19.7% and a clinical benefit rate of 42.4%, indicating promising efficacy in a heavily pretreated population.

Abemaciclib was well tolerated, with the most common side effects being diarrhea, fatigue, and nausea, and only 7.6% of patients discontinued treatment due to adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Dickler, MN., Tolaney, SM., Rugo, HS., et al.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. [2019]