Abemaciclib and Radiation Therapy for Breast Cancer

Recruiting at 6 trial locations

Overseen By Lior Braunstein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Hormonal therapy, Abemaciclib

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Pregnancy, Severe renal impairment, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose of abemaciclib, a drug used with radiation therapy, for individuals with a specific type of breast cancer that is hormone receptor-positive and HER2-negative. It targets those with metastatic breast cancer that has spread to the bones and who plan to undergo radiation treatment. Participants must have a prior diagnosis of this breast cancer type and a treatment plan that includes abemaciclib following radiation therapy. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, providing participants the chance to contribute to groundbreaking research.

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

You may need to stop taking certain medications. If you are on a CDK4/6 inhibitor like palbociclib or ribociclib, you must stop it at least 7 days before starting the trial. However, you can continue taking hormonal therapy and abemaciclib before enrollment.

Is there any evidence suggesting that abemaciclib is likely to be safe for humans?

Research has shown that abemaciclib, a drug often used for breast cancer, has been studied for its safety in people. Most patients have tolerated it well. Some studies indicate that common side effects include diarrhea, tiredness, and nausea. Proper care can usually manage these side effects.

In some cases, abemaciclib has already received approval for treating certain types of breast cancer. This approval suggests it is generally safe for those conditions, although each patient is different.

Radiation therapy, often used with other treatments like abemaciclib, also has a known safety record. Side effects can include skin irritation and tiredness, but these are usually temporary.

Since this study is in its early research phase, the treatment's safety is still under close observation. This phase aims to find the best dose with the fewest side effects. Researchers will monitor participants carefully to ensure their safety.

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for HR+, HER2- metastatic breast cancer, which typically include hormone therapy and chemotherapy, Abemaciclib works by specifically targeting and inhibiting certain proteins called CDK4 and CDK6. These proteins are involved in cell division, so blocking them might help slow down or stop cancer cells from multiplying. Researchers are excited about Abemaciclib because it can be taken orally, offering a more convenient option compared to traditional intravenous therapies, and it may enhance the effectiveness of radiation therapy when used in combination. This combined approach could potentially provide better control of the cancer with fewer side effects.

What evidence suggests that abemaciclib might be an effective treatment for breast cancer?

Research has shown that abemaciclib effectively treats hormone receptor-positive (HR+) and HER2-negative breast cancer. Studies have found that abemaciclib slows cancer cell growth by blocking proteins essential for cell division, helping to prevent cancer from spreading. In earlier trials, patients who took abemaciclib with other treatments experienced longer periods without cancer progression compared to those who did not. In this trial, participants with HR+, HER2- metastatic breast cancer will receive abemaciclib alongside radiation therapy. This promising evidence suggests that abemaciclib may be a valuable addition to radiation and hormone therapy for this type of breast cancer.

Who Is on the Research Team?

Lior Braunstein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic breast cancer. Participants will be receiving hormone therapy and radiation alongside the study treatment.

Inclusion Criteria

Women of childbearing potential must agree to use highly effective contraception, men must use a barrier method of contraception

I can take pills by mouth.

I am currently on hormonal therapy and abemaciclib.

Exclusion Criteria

I have a long-term stomach problem that mainly causes diarrhea.

My cancer has caused severe pressure on my spinal cord.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib in combination with hormone therapy and radiation therapy to determine the maximum tolerated dose

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The study is testing various doses of a drug called Abemaciclib to determine the most effective dose when used with hormone therapy and radiation in treating metastatic breast cancer.

How Is the Trial Designed?

Group I: Participants with HR+, HER2- metastatic breast cancer Experimental Treatment 2 Interventions

Participants will have a diagnosis of HR+, HER2- metastatic breast cancer. Abemaciclib, orally every 12 (± 2) hours beginning on the day of simulation thru the final day of radiotherapy for a maximum 28-day course. Radiation therapy, 27Gy in 3 daily fractions or 30Gy in 5 daily fractions completed entirely within 28 days of simulation.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

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]

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 the nextMONARCH study involving women with endocrine-refractory HR+, HER2- metastatic breast cancer, abemaciclib showed a median progression-free survival (PFS) of 9.1 months when combined with tamoxifen, but this was not significantly better than the 7.4 months PFS with abemaciclib alone plus prophylactic loperamide.

The study found that the incidence and severity of diarrhea, a common side effect of abemaciclib, were manageable with dose adjustments and antidiarrheal medication, indicating that the treatment can be tolerated while maintaining its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. Hamilton, E., Cortes, J., Ozyilkan, O., et al.[2021]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

In a phase III study involving 5,637 patients with high-risk HR+, HER2- early breast cancer, the combination of abemaciclib and standard endocrine therapy significantly improved invasive disease-free survival (IDFS) compared to endocrine therapy alone, with a 2-year IDFS rate of 92.2% versus 88.7%.

Abemaciclib, when added to endocrine therapy, is the first CDK4/6 inhibitor shown to effectively reduce the risk of early recurrence in this patient population, and its safety profile aligns with previously established data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). Johnston, SRD., Harbeck, N., Hegg, R., et al.[2022]

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 a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

In a study involving 101 Japanese patients with advanced breast cancer, abemaciclib was found to be well tolerated, with all patients experiencing at least one treatment-emergent adverse event (TEAE), primarily manageable with interventions.

Common TEAEs included diarrhea (95.0% of patients), neutropenia (75.2%), and increased liver enzymes (ALT and AST), with most severe cases occurring early in treatment and effectively managed through dose adjustments and medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels. Masuda, N., Chen, Y., Kawaguchi, T., et al.[2022]

Citations