Imaging and Abemaciclib for Breast Cancer

Recruiting at 3 trial locations

Overseen By Hannah Linden, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: GnRH agonist

Must not be taking: Investigational agents

Disqualifiers: Hepatic-only metastases, Unstable brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 5

Duration: Up to 2 years

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a special imaging scan can predict the effectiveness of a breast cancer treatment that combines the drug abemaciclib (also known as Verzenio, LY2835219, or Ramiven) with hormone therapy. Abemaciclib inhibits certain proteins, which can slow or stop tumor growth in hormone receptor-positive (HR+) and HER2-negative breast cancer. The trial employs FFNP-PET/CT scans to provide a clearer picture of cancer location. It suits individuals with metastatic or locally advanced breast cancer that cannot be surgically removed and who meet specific medical criteria related to their cancer type and treatment history. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) of at least 2 weeks from chemotherapy or radiation, 2 weeks or 5 half-lives from oral SERD, 8 weeks from oral SERM, and 16 weeks from intramuscular SERD. You may continue taking LHRH agonists to remain post-menopausal without a need for washout.

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

Studies have shown that abemaciclib, also known as Verzenio, is generally well-tolerated in people with certain types of breast cancer. Research indicates that the most common side effects include diarrhea, tiredness, and nausea, but these can usually be managed. Abemaciclib has been used in other treatments and has demonstrated a consistent safety record.

Its FDA approval for a specific type of breast cancer (hormone receptor-positive, HER2 negative) suggests a well-established safety profile. However, like any treatment, risks exist, and discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Abemaciclib is unique because it targets specific proteins called cyclin-dependent kinases 4 and 6 (CDK4/6), which play a crucial role in cell division. Unlike traditional chemotherapy that targets all rapidly dividing cells, abemaciclib is more selective, aiming to halt the growth of cancer cells while sparing healthy ones. Researchers are excited because this targeted approach could potentially improve outcomes with fewer side effects compared to conventional treatments like chemotherapy. Additionally, the combination with estradiol and imaging techniques allows for a more personalized treatment, potentially identifying which patients will benefit the most.

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

Research has shown that abemaciclib, when combined with hormone therapy, significantly improves survival in patients with hormone receptor positive (HR+), HER2 negative breast cancer. Studies have found that two years of treatment with abemaciclib and hormone therapy leads to a noticeable increase in survival rates. This is the first treatment in over twenty years to offer such benefits for this type of breast cancer. In this trial, participants will receive abemaciclib along with estradiol and other hormone therapies chosen by the treating physician. Abemaciclib blocks certain proteins that help cancer cells grow, which can slow down or stop tumor growth. This makes it a promising option for patients with this specific type of breast cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Hannah Linden

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for individuals with advanced hormone receptor-positive, HER2-negative breast cancer. Participants should be suitable for functional imaging and abemaciclib treatment combined with endocrine therapy. Specific eligibility details are not provided.

Inclusion Criteria

Creatinine clearance >= 30 mL/min

Women of childbearing potential must agree to use adequate contraception (barrier method of birth control, abstinence) prior to study entry and for the duration of study participation

I agree to let my doctor use my stored cancer tissue and blood samples for testing.

Exclusion Criteria

My brain metastases are treated and stable.

I have HIV but my CD4+ T-cell count is above 350 and I haven't had an AIDS-related infection in the last year.

I have not taken abemaciclib for metastatic cancer or in the last 2 years after adjuvant treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging and Estradiol Administration

Participants receive FFNP IV and undergo PET/CT imaging at baseline, followed by estradiol administration and another round of FFNP IV and PET/CT imaging

1 week

2 visits (in-person)

Treatment

Participants receive abemaciclib orally twice daily on days 1-28 of each cycle, with cycles repeating every 28 days, and receive endocrine therapy of the treating physician's choice

Up to 2 years

Monthly visits (in-person) with additional diagnostic imaging every 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The study tests if FFNP-PET/CT imaging can predict the response to abemaciclib plus endocrine therapy in treating certain breast cancers. Abemaciclib blocks proteins that may slow tumor growth, while endocrine therapy affects hormones related to cancer growth.

How Is the Trial Designed?

Group I: Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET) Experimental Treatment 14 Interventions

Patients receive FFNP IV and undergo PET/CT imaging at baseline. Patients then receive estradiol orally Q8H over a 24-hour period, followed again by FFNP IV and PET/CT imaging. Patients then receive abemaciclib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive ET of the treating physician choice. Patients also receive FDG IV and undergo PET/CT imaging at baseline, with additional diagnostic imaging for tumor assessment every 3 cycles, and undergo blood sample collection throughout the study.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

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]

In a study of 22,048 patients with high-risk HR+/HER2- breast cancer, only 13% of those with one or two positive sentinel lymph nodes (SLNs) without high-risk features had four or more positive lymph nodes after surgery, indicating that many patients may not need further invasive procedures to determine eligibility for abemaciclib treatment.

The findings suggest that patients with one positive SLN without high-risk features should not undergo axillary lymph node dissection (ALND) solely to assess candidacy for abemaciclib, as it may lead to unnecessary surgical overtreatment and associated morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should patients with hormone receptor-positive, HER2-negative breast cancer and one or two positive sentinel nodes undergo axillary dissection to determine candidacy for adjuvant abemaciclib? Williams, AD., Ruth, K., Shaikh, SS., et al.[2023]

In a study involving 5632 patients with early breast cancer, abemaciclib combined with endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in premenopausal patients, showing a 42.2% and 40.3% reduction in risk, respectively.

The safety profile of abemaciclib in premenopausal patients was consistent with the overall safety data, indicating that it is a safe and effective treatment option for this subgroup of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2-, node-positive, high-risk early breast cancer. Paluch-Shimon, S., Neven, P., Huober, J., et al.[2023]

Abemaciclib, used for treating advanced breast cancer, was generally well tolerated, with the most common adverse event being diarrhea, affecting 42.8% of patients, which was manageable with medications and dose adjustments.

Importantly, dose reductions or early onset of adverse events like diarrhea and neutropenia did not negatively impact progression-free survival, indicating that patients can continue treatment effectively despite these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. Rugo, HS., Huober, J., García-Sáenz, JA., et al.[2023]

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 the neoMONARCH study, postmenopausal women with HR+/HER2- breast cancer showed significant decreases in Ki67 expression and achieved higher rates of complete cell-cycle arrest when treated with abemaciclib alone or in combination with anastrozole compared to anastrozole alone.

The combination therapy not only inhibited cancer cell growth but also enhanced immune activation, suggesting a dual mechanism of action that could improve treatment outcomes, while the most common side effects were manageable gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. Hurvitz, SA., Martin, M., Press, MF., et al.[2023]

The monarchE study focused on patients with high-risk HR+, HER2- early breast cancer, showing that adjuvant treatment with abemaciclib plus endocrine therapy (ET) significantly benefits these patients.

This evidence supports the use of abemaciclib in routine clinical practice for patients identified with high-risk features, potentially improving outcomes for those at risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1. Toi, M., Boyle, F., Im, YH., et al.[2023]

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[2022]

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

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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 ...

2. investor.lilly.com investor.lilly.com/node/52836/pdf

Lilly's Verzenio® (abemaciclib) increases overall survival ... Treatment with two years of Verzenio plus endocrine therapy (ET) demonstrated a statistically significant and clinically meaningful improvement ...

3. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... Verzenio is the first contemporary therapy in over two decades to demonstrate a significant overall survival benefit in adjuvant HR+, HER2−, ...

4. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00263-7/fulltext

Prevalence and prognosis of patients with breast cancer ... ∙ et al. Review of the monarchE trial suggests no evidence to support use of adjuvant abemaciclib in women with breast cancer. Lancet Oncol ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04031885

NCT04031885 | A Study of Abemaciclib (LY2835219) in ... The reason for this study is to compare the efficacy of abemaciclib, in combination with fulvestrant, to that of physician's choice of chemotherapy in women ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK609559/

Abemaciclib (Verzenio) - NCBI Bookshelf - NIH ... breast cancer setting. The safety profile of abemaciclib + ET in the MonarchE trial was generally consistent with known safety profile previously reported ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000RiskR.pdf

208716Orig1s000 - accessdata.fda.gov 5 Risk Assessment & Safe-Use Conditions. The safety profile of abemaciclib for the proposed indications is based on safety data from the Phase 3.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH Data from the monarchE trial show a similar safety profile of adjuvant abemaciclib in the early breast cancer setting. Overall, the most common ...