High-Dose Abemaciclib for Early-Stage Breast Cancer

Not currently recruiting at 12 trial locations

Overseen By Erica Mayer, MD, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Aromatase inhibitors, Tamoxifen

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Node-negative cancer, Inflammatory cancer, 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

Compensation: Varies

Number of Visits: 3

Duration: 24 cycles (approximately 2 years)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether increasing the dose of abemaciclib, a breast cancer drug, can reduce side effects and improve tolerance for patients with early-stage, high-risk hormone receptor-positive breast cancer. Researchers compare this higher dose to the standard dose of abemaciclib, used alongside common breast cancer treatments like tamoxifen and aromatase inhibitors (such as anastrozole, letrozole, or exemestane). Suitable candidates have undergone surgery for stage II or III breast cancer within the last 16 months and are already eligible for usual follow-up treatments like hormone therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medications that strongly interact with CYP3A4, a liver enzyme, unless you stop them for a certain period before joining the study.

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

Research shows that abemaciclib, when combined with hormone therapy, is generally well-tolerated by patients with early-stage breast cancer. Studies have found that the side effects of this treatment are manageable and reversible. Patients report that these side effects do not last long.

Although researchers are still testing abemaciclib for safety, the FDA has already approved it for other cancer treatments, indicating a known safety profile.

The other treatments in the trial, such as tamoxifen and anastrozole, are standard hormone therapies for breast cancer and have been used safely for many years. They are generally well-tolerated and have predictable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for early-stage breast cancer, which typically includes hormonal therapies like tamoxifen and aromatase inhibitors, abemaciclib is unique because it targets a specific protein involved in cell division called CDK4/6. This targeted action helps to slow down or stop the growth of cancer cells more directly. Researchers are excited about abemaciclib because it has the potential to enhance the effectiveness of existing hormone therapies, offering a more robust strategy in combating early-stage breast cancer.

What evidence suggests that high-dose abemaciclib might be an effective treatment for early-stage breast cancer?

Research has shown that adding abemaciclib to hormone therapy can help patients with high-risk early-stage hormone receptor-positive breast cancer live longer. In this trial, participants will receive a predetermined dose of abemaciclib alongside endocrine therapy. Studies found that survival rates at 5, 6, and 7 years were 91.2%, 89.2%, and 86.8% with the combination treatment, compared to 90.2%, 87.9%, and 85.0% with hormone therapy alone. This suggests abemaciclib may offer a survival advantage over hormone therapy alone. Additionally, abemaciclib extended life in similar patient groups over two years of treatment. These findings suggest it could be an effective option for early-stage breast cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Erica L. Mayer, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with high-risk hormone receptor positive, HER2- early-stage breast cancer. They must have completed surgery within the last 16 months, may already be on endocrine therapy, and should not have had chemotherapy or radiotherapy recently. Participants need to use effective nonhormonal contraception and cannot be pregnant or nursing.

Inclusion Criteria

I can swallow and keep down pills.

I finished my radiotherapy at least 14 days ago and have recovered from its immediate effects.

I am using reliable birth control methods during and 3 months after the study.

Exclusion Criteria

I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

Receipt of an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research judged by the sponsor-investigator not to be scientifically or medically compatible with this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive abemaciclib and endocrine therapy in cycles, with regular clinic visits for assessments

24 cycles (approximately 2 years)

Day 1 of Cycles 1, 2, and 3; Day 15 of Cycles 1 and 2; Every three cycles after Cycle 3 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

End of Treatment

Final assessments including blood tests, questionnaires, and stool sample collection

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Anastrozole/Letrozole
• Exemestane
• LHRH Agonist
• Tamoxifen

Trial Overview The TRADE study is testing a new way of giving abemaciclib where doses increase over time. This approach aims to see if it's easier for patients to handle than the standard dose. The trial includes other drugs like Tamoxifen and aromatase inhibitors that are commonly used in breast cancer treatment.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 6 Interventions

Study procedures will be conducted as follows: * Cycles 1 - 24 * Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. * Endocrine therapy 1 x per day. * In clinic visits with blood tests, questionnaires, and assessments: * Day 1 of Cycles 1, 2, and 3 * Day 15 of Cycles 1 and 2 * Every three cycles after Cycle 3 Day 1. * End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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 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 MONARCH 3 study involving 493 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, abemaciclib combined with a nonsteroidal aromatase inhibitor significantly improved progression-free survival (PFS) to 28.18 months compared to 14.76 months for the placebo group.

The objective response rate (ORR) was also higher in the abemaciclib group at 61.0% versus 45.5% in the placebo group, with a tolerable safety profile, although some patients experienced grade ≥3 adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Johnston, S., Martin, M., Di Leo, A., 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]

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 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]

Citations

1. ajmc.com ajmc.com/view/abemaciclib-plus-endocrine-therapy-improves-overall-survival-in-high-risk-early-breast-cancer

Abemaciclib Plus Endocrine Therapy Improves Overall ... At 60, 72, and 84 months, OS rates were 91.2%, 89.2%, and 86.8% in the abemaciclib plus ET arm vs 90.2%, 87.9%, and 85.0% in the ET arm. In both ...

2. 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+, ... Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, HER2-, high-risk early breast cancer with two years of treatment. Eli Lilly and ...

3. 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 ...

4. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-early-breast-cancer

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly Kaplan-Meier curve of overall survival in Cohort 1 for the monarchE phase 3 global trial, showing a 16.5% reduction in risk of death (the hazard ratio was 0.835 ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/verzenio-kisqali-positive-long-term-results-early-breast-cancer-trials

Verzenio and Kisqali Deliver Positive Long-Term Results ... Seven-year overall survival rate reached 86.8% with Verzenio versus 85% with ET alone. Kisqali plus ET achieved a 28.4% reduction in recurrence ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03155997

Study Details | NCT03155997 | Endocrine Therapy With or ... The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425049488

Overall Survival with Abemaciclib in Early Breast Cancer Patient reported outcomes findings confirm a tolerable and reversible toxicity profile. The long-term safety data compiled did not support any ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368096/

Practical Guidance on Abemaciclib in Combination with ... We provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)04932-4/fulltext

a phase II trial to assess the tolerability of abemaciclib dose ... Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE ...