High-Dose Abemaciclib for Early-Stage Breast Cancer

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)

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adjusting the dose of abemaciclib, along with hormone treatments, will cause fewer side effects and be easier for patients with early-stage high-risk hormone receptor positive breast cancer to handle. The treatment works by blocking proteins and hormones that help cancer grow. Abemaciclib has shown potential in improving survival outcomes and quality of life in patients with advanced hormone receptor-positive breast cancer.

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.

What data supports the effectiveness of the drug Abemaciclib for early-stage breast cancer?

Research shows that Abemaciclib, when combined with endocrine therapy, significantly reduces the risk of breast cancer coming back in patients with early-stage, hormone receptor-positive, HER2-negative breast cancer. It has been effective in both premenopausal and postmenopausal women, and its side effects are generally manageable. ^{1 2 3 4 5}

Is high-dose Abemaciclib safe for early-stage breast cancer?

Abemaciclib, used with endocrine therapy, is generally safe for early-stage breast cancer, with common side effects like diarrhea, infections, and low white blood cell counts. These side effects are usually manageable. ^{1 2 3 6 7}

What makes the drug Abemaciclib unique for early-stage breast cancer?

Abemaciclib is unique because it is a CDK4/6 inhibitor that, when combined with standard endocrine therapy, significantly reduces the risk of breast cancer recurrence in patients with hormone receptor-positive, HER2-negative early-stage breast cancer at high risk of recurrence. This combination therapy is particularly effective in both premenopausal and postmenopausal women, offering a valuable option beyond standard endocrine therapy alone. ^{1 2 3 5 6}

Research Team

Erica L. Mayer, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. Netherlands 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. [2022]

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

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

3. France pubmed.ncbi.nlm.nih.gov

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

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

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. [2023]

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

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

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

Discrepancies in estradiol levels in a premenopausal woman receiving abemaciclib despite ovarian function suppression and bilateral salpingo-oophorectomy. [2023]

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

Abemaciclib: First Global Approval. [2019]