Abemaciclib + SRS for Breast Cancer Brain Metastases

Recruiting at 1 trial location

Overseen By Kamran A Ahmed, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Endocrine therapy

Must not be taking: Abemaciclib

Disqualifiers: Leptomeningeal disease, Whole brain radiation, 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

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of the drug abemaciclib (Verzenio) and a type of targeted radiation called stereotactic radiosurgery (SRS) for individuals with breast cancer that has spread to the brain. The researchers aim to determine the safety and effectiveness of this treatment for patients with hormone receptor-positive (HR+) breast cancer that does not overexpress HER2. Individuals with up to 15 brain metastases who can take oral medications might be suitable candidates. The trial involves taking the drug and receiving radiation to the brain metastases. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that abemaciclib is generally well-tolerated by patients with brain metastases from hormone receptor-positive breast cancer. Studies have found that abemaciclib reaches effective levels in brain tissue, suggesting it can effectively target cancer cells there. The side effects reported for abemaciclib are similar to those seen in earlier studies, indicating they are usually manageable.

Stereotactic radiosurgery (SRS), a precise type of radiation therapy, has proven effective and safe for treating brain metastases, including those from breast cancer. Reports indicate it is highly effective at controlling tumors, either shrinking them or stopping their growth.

Together, these treatments have demonstrated that most patients can handle the side effects. This conclusion is based on earlier studies, providing a strong foundation of safety data for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of abemaciclib with stereotactic radiation therapy for treating breast cancer brain metastases because it offers a targeted approach that might enhance treatment effectiveness. Unlike traditional chemotherapy and whole-brain radiation, which can have widespread effects on the body and brain, abemaciclib is a CDK4/6 inhibitor that specifically targets cancer cell growth. This precision, coupled with the focused nature of stereotactic radiation, aims to minimize damage to healthy brain tissue while attacking the tumor more aggressively. This combination could potentially improve outcomes and reduce side effects compared to current standard treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer brain metastases?

Studies have shown that abemaciclib can reach effective levels in brain tissue, particularly for patients with HR+ breast cancer that has metastasized to the brain. This allows it to effectively target and block key proteins involved in cancer growth. Research indicates that patients treated with abemaciclib have experienced significant survival benefits. In this trial, participants will receive a combination of abemaciclib and stereotactic radiosurgery (SRS). SRS has effectively controlled small to medium-sized brain tumors, with success rates between 65% and 94%. Together, these treatments aim to improve outcomes for breast cancer patients with brain metastases. ^{1 2 3 6 7}

Who Is on the Research Team?

Heather Han, MD

Principal Investigator

Moffitt Cancer Center

Kamran A Ahmed, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with HR+/HER2- metastatic breast cancer brain metastases. Participants can have had prior radiation treatments if there's measurable disease not previously treated with radiation. They must be able to undergo stereotactic radiosurgery, have ≤ 15 brain lesions eligible for this treatment, and a performance status of 0 to 2. Women must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

If you can have babies, you need to have a negative pregnancy test within 7 days before starting the medicine abemaciclib.

I have a brain tumor or cavity from surgery that can be measured and is at least 0.5 cm big.

Exclusion Criteria

I am not pregnant or breastfeeding.

Prisoners or individuals who are involuntarily incarcerated

I haven't had any other cancer besides this one in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

One week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. Safety monitored by a 3+3 design.

1-2 weeks

Treatment Phase II

Continuation of abemaciclib and stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities.

Up to 12 months

Follow-up

Participants are monitored for intracranial progression free survival and other outcomes.

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Endocrine therapy
• Stereotactic Radiosurgery (SRS)

Trial Overview

The study tests the combination of abemaciclib and endocrine therapy alongside stereotactic radiosurgery (SRS) in patients with specific breast cancer that has spread to the brain. It's a single-arm study, meaning all participants receive the same treatment without comparison groups.

How Is the Trial Designed?

Group I: Phase 2: Radiation Therapy and Abemaciclib Experimental Treatment 3 Interventions

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities with continued abemaciclib.

Group II: Phase 1: Radiation Therapy and Abemaciclib Experimental Treatment 3 Interventions

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. In the phase I portion, safety will be monitored initially by a 3+3 design. If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., et al.[2022]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

A patient with hormone receptor-positive breast cancer and cystic brain metastases (CBM) showed partial remission after treatment with abemaciclib and fulvestrant, indicating potential efficacy of this combination therapy for CBM.

Despite the positive response in CBM, the patient continued to experience an increase in extracranial bone metastases, highlighting the complexity of treating metastatic breast cancer and the need for ongoing monitoring and treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with cystic brain metastases: A case report and literature review. Chu, Z.[2022]

In the MONARCH 2 study involving 669 women with advanced breast cancer, the combination of abemaciclib and fulvestrant significantly improved progression-free survival (PFS) to a median of 16.4 months compared to 9.3 months with fulvestrant alone.

The combination therapy also achieved a higher objective response rate (ORR) of 48.1% versus 21.3% in the control group, while maintaining a tolerable safety profile, with common side effects including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Sledge, GW., Toi, M., Neven, P., et al.[2022]

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]

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]

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]

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]

Citations

1.

academic.oup.com

academic.oup.com/oncolo/article/30/8/oyae274/7825842

Real-world outcomes in patients with brain metastases ...

In a previous phase II trial (NCT02308020), abemaciclib demonstrated clinical benefit in a subset of patients with HR+ metastatic breast cancer ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32694159/

A Phase II Study of Abemaciclib in Patients with Brain ...

Abemaciclib achieved therapeutic concentrations in brain metastases tissue, far exceeding those necessary for CDK4 and CDK6 inhibition. Further ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02308020

NCT02308020 | A Study of Abemaciclib (LY2835219) in ...

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive ...

4.

aacrjournals.org

aacrjournals.org/clincancerres/article/26/20/5310/82934/A-Phase-II-Study-of-Abemaciclib-in-Patients-with

A Phase II Study of Abemaciclib in Patients with Brain ...

Abemaciclib achieved therapeutic concentrations in brain metastases tissue, far exceeding those necessary for CDK4 and CDK6 inhibition. Further studies are ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ...

In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.1017

A phase II study of abemaciclib in patients (pts) with brain ...

Safety and tolerability were similar to previous reports for abemaciclib. Conclusions: Abemaciclib demonstrated intracranial clinical benefit in ...

7.

conference-correspondent.com

conference-correspondent.com/highlights/sabcs/sabcs-2017/abemaciclib-for-the-treatment-of-brain-metastases-secondary-to-hr-positive-breast-cancer

Abemaciclib for the Treatment of Brain Metastases ...

Abemaciclib demonstrated efficacy and an acceptable safety profile in treating brain metastases in hormone receptor (HR)-positive/HER2-negative breast ...